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Lee H, Cho HJ, Han Y, Lee SH. Mid- to long-term efficacy and safety of stem cell therapy for acute myocardial infarction: a systematic review and meta-analysis. Stem Cell Res Ther 2024; 15:290. [PMID: 39256845 PMCID: PMC11389242 DOI: 10.1186/s13287-024-03891-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 08/21/2024] [Indexed: 09/12/2024] Open
Abstract
BACKGROUND This comprehensive systematic review and meta-analysis investigated the mid- to long-term efficacy and safety of stem cell therapy in patients with acute myocardial infarction (AMI). METHODS The study encompassed 79 randomized controlled trials with 7103 patients, rendering it the most up-to-date and extensive analysis in this field. This study specifically focused on the impact of stem cell therapy on left ventricular ejection fraction (LVEF), major adverse cardiac events (MACE), and infarct size. RESULTS Stem cell therapy significantly improved LVEF at 6, 12, 24, and 36 months post-transplantation compared to control values, indicating its potential for long-term cardiac function enhancement. A trend toward reduced MACE occurrence was observed in the intervention groups, suggesting the potential of stem cell therapy to lower the risk of cardiovascular death, reinfarction, and stroke. Significant LVEF improvements were associated with long cell culture durations exceeding 1 week, particularly when combined with high injected cell quantities (at least 108 cells). No significant reduction in infarct size was observed. CONCLUSIONS This review highlights the potential of stem cell therapy as a promising therapeutic approach for patients with AMI, offering sustained LVEF improvement and a potential reduction in MACE risk. However, further research is required to optimize cell culture techniques, determine the optimal timing and dosage, and investigate procedural variations to maximize the efficacy and safety of stem cell therapy in this context.
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Affiliation(s)
- Hyeongsuk Lee
- College of Nursing, Research Institute of AI and Nursing Science, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, South Korea
| | - Hyun-Jai Cho
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Yeonjung Han
- College of Nursing, Research Institute of AI and Nursing Science, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, South Korea
| | - Seon Heui Lee
- College of Nursing, Research Institute of AI and Nursing Science, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, South Korea.
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2
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Cui X, Guo J, Yuan P, Dai Y, Du P, Yu F, Sun Z, Zhang J, Cheng K, Tang J. Bioderived Nanoparticles for Cardiac Repair. ACS NANO 2024; 18:24622-24649. [PMID: 39185722 DOI: 10.1021/acsnano.3c07878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/27/2024]
Abstract
Biobased therapy represents a promising strategy for myocardial repair. However, the limitations of using live cells, including the risk of immunogenicity of allogeneic cells and inconsistent therapeutic efficacy of autologous cells together with low stability, result in an unsatisfactory clinical outcomes. Therefore, cell-free strategies for cardiac tissue repair have been proposed as alternative strategies. Cell-free strategies, primarily based on the paracrine effects of cellular therapy, have demonstrated their potential to inhibit apoptosis, reduce inflammation, and promote on-site cell migration and proliferation, as well as angiogenesis, after an infarction and have been explored preclinically and clinically. Among various cell-free modalities, bioderived nanoparticles, including adeno-associated virus (AAV), extracellular vesicles, cell membrane-coated nanoparticles, and exosome-mimetic nanovesicles, have emerged as promising strategies due to their improved biological function and therapeutic effect. The main focus of this review is the development of existing cellular nanoparticles and their fundamental working mechanisms, as well as the challenges and opportunities. The key processes and requirements for cardiac tissue repair are summarized first. Various cellular nanoparticle modalities are further highlighted, together with their advantages and limitations. Finally, we discuss various delivery approaches that offer potential pathways for researchers and clinicians to translate cell-free strategies for cardiac tissue repair into clinical practice.
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Affiliation(s)
- Xiaolin Cui
- Cardiac and Osteochondral Tissue Engineering (COTE) Group, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China
| | - Jiacheng Guo
- Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Peiyu Yuan
- Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Yichen Dai
- Cardiac and Osteochondral Tissue Engineering (COTE) Group, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China
| | - Pengchong Du
- Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Fengyi Yu
- Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Zhaowei Sun
- Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Jinying Zhang
- Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Ke Cheng
- Department of Biomedical Engineering, Columbia University, New York, New York 10027, United States
| | - Junnan Tang
- Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
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Yahyazadeh R, Baradaran Rahimi V, Askari VR. Stem cell and exosome therapies for regenerating damaged myocardium in heart failure. Life Sci 2024; 351:122858. [PMID: 38909681 DOI: 10.1016/j.lfs.2024.122858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 06/13/2024] [Accepted: 06/18/2024] [Indexed: 06/25/2024]
Abstract
Finding novel treatments for cardiovascular diseases (CVDs) is a hot topic in medicine; cell-based therapies have reported promising news for controlling dangerous complications of heart disease such as myocardial infarction (MI) and heart failure (HF). Various progenitor/stem cells were tested in various in-vivo, in-vitro, and clinical studies for regeneration or repairing the injured tissue in the myocardial to accelerate the healing. Fetal, adult, embryonic, and induced pluripotent stem cells (iPSC) have revealed the proper potency for cardiac tissue repair. As an essential communicator among cells, exosomes with specific contacts (proteins, lncRNAs, and miRNAs) greatly promote cardiac rehabilitation. Interestingly, stem cell-derived exosomes have more efficiency than stem cell transplantation. Therefore, stem cells induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), cardiac stem cells (CDC), and skeletal myoblasts) and their-derived exosomes will probably be considered an alternative therapy for CVDs remedy. In addition, stem cell-derived exosomes have been used in the diagnosis/prognosis of heart diseases. In this review, we explained the advances of stem cells/exosome-based treatment, their beneficial effects, and underlying mechanisms, which will present new insights in the clinical field in the future.
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Affiliation(s)
- Roghayeh Yahyazadeh
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vafa Baradaran Rahimi
- Department of Cardiovascular Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Vahid Reza Askari
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
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4
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Sabe SA, Harris DD, Broadwin M, Sellke FW. Cardioprotection in cardiovascular surgery. Basic Res Cardiol 2024; 119:545-568. [PMID: 38856733 DOI: 10.1007/s00395-024-01062-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 05/31/2024] [Accepted: 06/01/2024] [Indexed: 06/11/2024]
Abstract
Since the invention of cardiopulmonary bypass, cardioprotective strategies have been investigated to mitigate ischemic injury to the heart during aortic cross-clamping and reperfusion injury with cross-clamp release. With advances in cardiac surgical and percutaneous techniques and post-operative management strategies including mechanical circulatory support, cardiac surgeons are able to operate on more complex patients. Therefore, there is a growing need for improved cardioprotective strategies to optimize outcomes in these patients. This review provides an overview of the basic principles of cardioprotection in the setting of cardiac surgery, including mechanisms of cardiac injury in the context of cardiopulmonary bypass, followed by a discussion of the specific approaches to optimizing cardioprotection in cardiac surgery, including refinements in cardiopulmonary bypass and cardioplegia, ischemic conditioning, use of specific anesthetic and pharmaceutical agents, and novel mechanical circulatory support technologies. Finally, translational strategies that investigate cardioprotection in the setting of cardiac surgery will be reviewed, with a focus on promising research in the areas of cell-based and gene therapy. Advances in this area will help cardiologists and cardiac surgeons mitigate myocardial ischemic injury, improve functional post-operative recovery, and optimize clinical outcomes in patients undergoing cardiac surgery.
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Affiliation(s)
- Sharif A Sabe
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI, 02905, USA
| | - Dwight D Harris
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI, 02905, USA
| | - Mark Broadwin
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI, 02905, USA
| | - Frank W Sellke
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI, 02905, USA.
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5
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Kumar R, Mishra N, Tran T, Kumar M, Vijayaraghavalu S, Gurusamy N. Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics. Cells 2024; 13:855. [PMID: 38786076 PMCID: PMC11120430 DOI: 10.3390/cells13100855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 05/13/2024] [Accepted: 05/15/2024] [Indexed: 05/25/2024] Open
Abstract
Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs' potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.
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Affiliation(s)
- Rishabh Kumar
- Department of Biochemistry, Faculty of Science, University of Allahabad, Prayagraj 211002, India
| | - Nitin Mishra
- Department of Biochemistry, Faculty of Science, University of Allahabad, Prayagraj 211002, India
| | - Talan Tran
- Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328-2018, USA
| | - Munish Kumar
- Department of Biochemistry, Faculty of Science, University of Allahabad, Prayagraj 211002, India
| | | | - Narasimman Gurusamy
- Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328-2018, USA
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6
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Carvalho AB, Kasai-Brunswick TH, Campos de Carvalho AC. Advanced cell and gene therapies in cardiology. EBioMedicine 2024; 103:105125. [PMID: 38640834 PMCID: PMC11052923 DOI: 10.1016/j.ebiom.2024.105125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 04/01/2024] [Accepted: 04/04/2024] [Indexed: 04/21/2024] Open
Abstract
We review the evidence for the presence of stem/progenitor cells in the heart and the preclinical and clinical data using diverse cell types for the therapy of cardiac diseases. We highlight the failure of adult stem/progenitor cells to ameliorate heart function in most cardiac diseases, with the possible exception of refractory angina. The use of pluripotent stem cell-derived cardiomyocytes is analysed as a viable alternative therapeutic option but still needs further research at preclinical and clinical stages. We also discuss the use of direct reprogramming of cardiac fibroblasts into cardiomyocytes and the use of extracellular vesicles as therapeutic agents in ischemic and non-ischemic cardiac diseases. Finally, gene therapies and genome editing for the treatment of hereditary cardiac diseases, ablation of genes responsible for atherosclerotic disease, or modulation of gene expression in the heart are discussed.
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Affiliation(s)
- Adriana Bastos Carvalho
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa, Universidade Federal do RIo de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Tais Hanae Kasai-Brunswick
- Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO), Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa, Universidade Federal do RIo de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Antonio Carlos Campos de Carvalho
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO), Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa, Universidade Federal do RIo de Janeiro, Rio de Janeiro, RJ, Brazil.
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7
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Vo QD, Saito Y, Nakamura K, Iida T, Yuasa S. Induced Pluripotent Stem Cell-Derived Cardiomyocytes Therapy for Ischemic Heart Disease in Animal Model: A Meta-Analysis. Int J Mol Sci 2024; 25:987. [PMID: 38256060 PMCID: PMC10815661 DOI: 10.3390/ijms25020987] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 01/07/2024] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
Ischemic heart disease (IHD) poses a significant challenge in cardiovascular health, with current treatments showing limited success. Induced pluripotent derived-cardiomyocyte (iPSC-CM) therapy within regenerative medicine offers potential for IHD patients, although its clinical impacts remain uncertain. This study utilizes meta-analysis to assess iPSC-CM outcomes in terms of efficacy and safety in IHD animal model studies. A meta-analysis encompassing PUBMED, ScienceDirect, Web of Science, and the Cochrane Library databases, from inception until October 2023, investigated iPSC therapy effects on cardiac function and safety outcomes. Among 51 eligible studies involving 1012 animals, despite substantial heterogeneity, the iPSC-CM transplantation improved left ventricular ejection fraction (LVEF) by 8.23% (95% CI, 7.15 to 9.32%; p < 0.001) compared to control groups. Additionally, cell-based treatment reduced the left ventricle fibrosis area and showed a tendency to reduce left ventricular end-systolic volume (LVESV) and end-diastolic volume (LVEDV). No significant differences emerged in mortality and arrhythmia risk between iPSC-CM treatment and control groups. In conclusion, this meta-analysis indicates iPSC-CM therapy's promise as a safe and beneficial intervention for enhancing heart function in IHD. However, due to observed heterogeneity, the efficacy of this treatment must be further explored through large randomized controlled trials based on rigorous research design.
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Affiliation(s)
- Quan Duy Vo
- Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (S.Y.)
| | - Yukihiro Saito
- Department of Cardiovascular Medicine, Okayama University Hospital, Okayama 700-8558, Japan
| | - Kazufumi Nakamura
- Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (S.Y.)
| | - Toshihiro Iida
- Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (S.Y.)
| | - Shinsuke Yuasa
- Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (S.Y.)
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Hsieh YK, Wang MT, Wang CY, Chen CF, Ko YL, Huang WC. Recent advances in the diagnosis and management of acute myocardial infarction. J Chin Med Assoc 2023; 86:950-959. [PMID: 37801590 DOI: 10.1097/jcma.0000000000001001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/08/2023] Open
Abstract
With the discovery of new biomarkers for the early detection of acute myocardial infarction (AMI), advancements in valid medication, and percutaneous coronary intervention (PCI), the overall prognosis of AMI has improved remarkably. Nevertheless, challenges remain which require more difficult work to overcome. Novel diagnostic and therapeutic techniques include new AMI biomarkers, hypothermia therapy, supersaturated oxygen (SSO 2 ) therapy, targeted anti-inflammatory therapy, targeted angiogenesis therapy, and stem cell therapy. With these novel methods, we believe that the infarction size after AMI will decrease, and myocardial injury-associated ventricular remodeling may be avoided. This review focuses on novel advances in the diagnosis and management of AMI.
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Affiliation(s)
- Yi-Keng Hsieh
- Department of Critical Care Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
- Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
- School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan, ROC
| | - Mei-Tzu Wang
- Department of Critical Care Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
- School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan, ROC
| | - Chien-Ying Wang
- School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan, ROC
- Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of Trauma, Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Exercise and Health Sciences, University of Taipei, Taipei, Taiwan, ROC
| | - Cheng-Fong Chen
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Exercise and Health Sciences, University of Taipei, Taipei, Taiwan, ROC
| | - Yu-Ling Ko
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Wei-Chun Huang
- Department of Critical Care Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
- Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
- Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan, ROC
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9
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Amini H, Namjoo AR, Narmi MT, Mardi N, Narimani S, Naturi O, Khosrowshahi ND, Rahbarghazi R, Saghebasl S, Hashemzadeh S, Nouri M. Exosome-bearing hydrogels and cardiac tissue regeneration. Biomater Res 2023; 27:99. [PMID: 37803483 PMCID: PMC10559618 DOI: 10.1186/s40824-023-00433-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 09/18/2023] [Indexed: 10/08/2023] Open
Abstract
BACKGROUND In recent years, cardiovascular disease in particular myocardial infarction (MI) has become the predominant cause of human disability and mortality in the clinical setting. The restricted capacity of adult cardiomyocytes to proliferate and restore the function of infarcted sites is a challenging issue after the occurrence of MI. The application of stem cells and byproducts such as exosomes (Exos) has paved the way for the alleviation of cardiac tissue injury along with conventional medications in clinics. However, the short lifespan and activation of alloreactive immune cells in response to Exos and stem cells are the main issues in patients with MI. Therefore, there is an urgent demand to develop therapeutic approaches with minimum invasion for the restoration of cardiac function. MAIN BODY Here, we focused on recent data associated with the application of Exo-loaded hydrogels in ischemic cardiac tissue. Whether and how the advances in tissue engineering modalities have increased the efficiency of whole-based and byproducts (Exos) therapies under ischemic conditions. The integration of nanotechnology and nanobiology for designing novel smart biomaterials with therapeutic outcomes was highlighted. CONCLUSION Hydrogels can provide suitable platforms for the transfer of Exos, small molecules, drugs, and other bioactive factors for direct injection into the damaged myocardium. Future studies should focus on the improvement of physicochemical properties of Exo-bearing hydrogel to translate for the standard treatment options.
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Affiliation(s)
- Hassan Amini
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of General and Vascular Surgery, Tabriz University of Medical Sciences, Tabriz, 51548/53431, Iran
| | - Atieh Rezaei Namjoo
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Taghavi Narmi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Narges Mardi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samaneh Narimani
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ozra Naturi
- Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran
| | - Nafiseh Didar Khosrowshahi
- Stem Cell and Tissue Engineering Research Laboratory, Sahand University of Technology, Tabriz, 51335-1996, Iran
| | - Reza Rahbarghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, 51548/53431, Iran.
| | - Solmaz Saghebasl
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, 51548/53431, Iran.
| | - Shahriar Hashemzadeh
- Department of General and Vascular Surgery, Tabriz University of Medical Sciences, Tabriz, 51548/53431, Iran.
| | - Mohammad Nouri
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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10
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Lintao RCV, Kammala AK, Radnaa E, Bettayeb M, Vincent KL, Patrikeev I, Yaklic J, Bonney EA, Menon R. Characterization of fetal microchimeric immune cells in mouse maternal hearts during physiologic and pathologic pregnancies. Front Cell Dev Biol 2023; 11:1256945. [PMID: 37808080 PMCID: PMC10556483 DOI: 10.3389/fcell.2023.1256945] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 09/13/2023] [Indexed: 10/10/2023] Open
Abstract
Introduction: During pregnancy, fetal cells can be incorporated into maternal tissues (fetal microchimerism), where they can persist postpartum. Whether these fetal cells are beneficial or detrimental to maternal health is unknown. This study aimed to characterize fetal microchimeric immune cells in the maternal heart during pregnancy and postpartum, and to identify differences in these fetal microchimeric subpopulations between normal and pregnancies complicated by spontaneous preterm induced by ascending infection. Methods: A Cre reporter mouse model, which when mated with wild-type C57BL/6J females resulted in cells and tissues of progeny expressing red fluorescent protein tandem dimer Tomato (mT+), was used to detect fetal microchimeric cells. On embryonic day (E)15, 104 colony-forming units (CFU) E. coli was administered intravaginally to mimic ascending infection, with delivery on or before E18.5 considered as preterm delivery. A subset of pregnant mice was sacrificed at E16 and postpartum day 28 to harvest maternal hearts. Heart tissues were processed for immunofluorescence microscopy and high-dimensional mass cytometry by time-of-flight (CyTOF) using an antibody panel of immune cell markers. Changes in cardiac physiologic parameters were measured up to 60 days postpartum via two-dimensional echocardiography. Results: Intravaginal E. coli administration resulted in preterm delivery of live pups in 70% of the cases. mT + expressing cells were detected in maternal uterus and heart, implying that fetal cells can migrate to different maternal compartments. During ascending infection, more fetal antigen-presenting cells (APCs) and less fetal hematopoietic stem cells (HSCs) and fetal double-positive (DP) thymocytes were observed in maternal hearts at E16 compared to normal pregnancy. These HSCs were cleared while DP thymocytes persisted 28 days postpartum following an ascending infection. No significant changes in cardiac physiologic parameters were observed postpartum except a trend in lowering the ejection fraction rate in preterm delivered mothers. Conclusion: Both normal pregnancy and ascending infection revealed distinct compositions of fetal microchimeric immune cells within the maternal heart, which could potentially influence the maternal cardiac microenvironment via (1) modulation of cardiac reverse modeling processes by fetal stem cells, and (2) differential responses to recognition of fetal APCs by maternal T cells.
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Affiliation(s)
- Ryan C. V. Lintao
- Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
- Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila, Philippines
| | - Ananth Kumar Kammala
- Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Enkhtuya Radnaa
- Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Mohamed Bettayeb
- Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Kathleen L. Vincent
- Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
- Biomedical Engineering and Imaging Sciences Group, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Igor Patrikeev
- Biomedical Engineering and Imaging Sciences Group, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Jerome Yaklic
- Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Elizabeth A. Bonney
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Larner College of Medicine, The University of Vermont, Burlington, VT, United States
| | - Ramkumar Menon
- Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
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11
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Pezhouman A, Nguyen NB, Kay M, Kanjilal B, Noshadi I, Ardehali R. Cardiac regeneration - Past advancements, current challenges, and future directions. J Mol Cell Cardiol 2023; 182:75-85. [PMID: 37482238 DOI: 10.1016/j.yjmcc.2023.07.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 07/13/2023] [Accepted: 07/18/2023] [Indexed: 07/25/2023]
Abstract
Cardiovascular disease is the leading cause of mortality and morbidity worldwide. Despite improvements in the standard of care for patients with heart diseases, including innovation in pharmacotherapy and surgical interventions, none have yet been proven effective to prevent the progression to heart failure. Cardiac transplantation is the last resort for patients with severe heart failure, but donor shortages remain a roadblock. Cardiac regenerative strategies include cell-based therapeutics, gene therapy, direct reprogramming of non-cardiac cells, acellular biologics, and tissue engineering methods to restore damaged hearts. Significant advancements have been made over the past several decades within each of these fields. This review focuses on the advancements of: 1) cell-based cardiac regenerative therapies, 2) the use of noncoding RNA to induce endogenous cell proliferation, and 3) application of bioengineering methods to promote retention and integration of engrafted cells. Different cell sources have been investigated, including adult stem cells derived from bone marrow and adipose cells, cardiosphere-derived cells, skeletal myoblasts, and pluripotent stem cells. In addition to cell-based transplantation approaches, there have been accumulating interest over the past decade in inducing endogenous CM proliferation for heart regeneration, particularly with the use of noncoding RNAs such as miRNAs and lncRNAs. Bioengineering applications have focused on combining cell-transplantation approaches with fabrication of a porous, vascularized scaffold using biomaterials and advanced bio-fabrication techniques that may offer enhanced retention of transplanted cells, with the hope that these cells would better engraft with host tissue to improve cardiac function. This review summarizes the present status and future challenges of cardiac regenerative therapies.
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Affiliation(s)
- Arash Pezhouman
- Baylor College of Medicine, Department of Medicine, Division of Cardiology, Houston, Texas 77030, United States; Texas Heart Institute, Houston, Texas 77030, United States
| | - Ngoc B Nguyen
- Baylor College of Medicine, Department of Internal Medicine, Houston, Texas 77030, United States
| | - Maryam Kay
- Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA 90095, United States
| | - Baishali Kanjilal
- Department of Bioengineering, University of California, Riverside, Riverside, CA 92521, United States
| | - Iman Noshadi
- Department of Bioengineering, University of California, Riverside, Riverside, CA 92521, United States
| | - Reza Ardehali
- Baylor College of Medicine, Department of Medicine, Division of Cardiology, Houston, Texas 77030, United States; Texas Heart Institute, Houston, Texas 77030, United States.
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12
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Abubakar M, Masood MF, Javed I, Adil H, Faraz MA, Bhat RR, Fatima M, Abdelkhalek AM, Buccilli B, Raza S, Hajjaj M. Unlocking the Mysteries, Bridging the Gap, and Unveiling the Multifaceted Potential of Stem Cell Therapy for Cardiac Tissue Regeneration: A Narrative Review of Current Literature, Ethical Challenges, and Future Perspectives. Cureus 2023; 15:e41533. [PMID: 37551212 PMCID: PMC10404462 DOI: 10.7759/cureus.41533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/06/2023] [Indexed: 08/09/2023] Open
Abstract
Revolutionary advancements in regenerative medicine have brought stem cell therapy to the forefront, offering promising prospects for the regeneration of ischemic cardiac tissue. Yet, its full efficacy, safety, and role in treating ischemic heart disease (IHD) remain limited. This literature review explores the intricate mechanisms underlying stem cell therapy. Furthermore, we unravel the innovative approaches employed to bolster stem cell survival, enhance differentiation, and seamlessly integrate them within the ischemic cardiac tissue microenvironment. Our comprehensive analysis uncovers how stem cells enhance cell survival, promote angiogenesis, and modulate the immune response. Stem cell therapy harnesses a multifaceted mode of action, encompassing paracrine effects and direct cell replacement. As our review progresses, we underscore the imperative for standardized protocols, comprehensive preclinical and clinical studies, and careful regulatory considerations. Lastly, we explore the integration of tissue engineering and genetic modifications, envisioning a future where stem cell therapy reigns supreme in regenerative medicine.
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Affiliation(s)
- Muhammad Abubakar
- Department of Internal Medicine, Ameer-Ud-Din Medical College, Lahore General Hospital, Lahore, PAK
- Department of Internal Medicine, Siddique Sadiq Memorial Trust Hospital, Gujranwala, PAK
| | | | - Izzah Javed
- Department of Internal Medicine, Ameer-Ud-Din Medical College, Lahore General Hospital, Lahore, PAK
| | - Hira Adil
- Department of Community Medicine, Khyber Girls Medical College, Hayatabad, PAK
| | - Muhammad Ahmad Faraz
- Department of Forensic Medicine, Post Graduate Medical Institute, Lahore General Hospital, Lahore, PAK
| | - Rakshita Ramesh Bhat
- Department of Medical Oncology, Mangalore Institute of Oncology, Mangalore, IND
- Department of Internal Medicine, Bangalore Medical College and Research Institute, Bangalore, IND
| | - Mahek Fatima
- Department of Internal Medicine, Osmania Medical College, Hyderabad, IND
| | | | - Barbara Buccilli
- Department of Human Neuroscience, Sapienza University of Rome, Rome, ITA
| | - Saud Raza
- Department of Internal Medicine, Ameer-Ud-Din Medical College, Lahore General Hospital, Lahore, PAK
| | - Mohsin Hajjaj
- Department of Internal Medicine, Jinnah Hospital Lahore, Lahore, PAK
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13
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Leancă SA, Afrăsânie I, Crișu D, Matei IT, Duca ȘT, Costache AD, Onofrei V, Tudorancea I, Mitu O, Bădescu MC, Șerban LI, Costache II. Cardiac Reverse Remodeling in Ischemic Heart Disease with Novel Therapies for Heart Failure with Reduced Ejection Fraction. Life (Basel) 2023; 13:1000. [PMID: 37109529 PMCID: PMC10143569 DOI: 10.3390/life13041000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 04/03/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Despite the improvements in the treatment of coronary artery disease (CAD) and acute myocardial infarction (MI) over the past 20 years, ischemic heart disease (IHD) continues to be the most common cause of heart failure (HF). In clinical trials, over 70% of patients diagnosed with HF had IHD as the underlying cause. Furthermore, IHD predicts a worse outcome for patients with HF, leading to a substantial increase in late morbidity, mortality, and healthcare costs. In recent years, new pharmacological therapies have emerged for the treatment of HF, such as sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, selective cardiac myosin activators, and oral soluble guanylate cyclase stimulators, demonstrating clear or potential benefits in patients with HF with reduced ejection fraction. Interventional strategies such as cardiac resynchronization therapy, cardiac contractility modulation, or baroreflex activation therapy might provide additional therapeutic benefits by improving symptoms and promoting reverse remodeling. Furthermore, cardiac regenerative therapies such as stem cell transplantation could become a new therapeutic resource in the management of HF. By analyzing the existing data from the literature, this review aims to evaluate the impact of new HF therapies in patients with IHD in order to gain further insight into the best form of therapeutic management for this large proportion of HF patients.
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Affiliation(s)
- Sabina Andreea Leancă
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Irina Afrăsânie
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Daniela Crișu
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Iulian Theodor Matei
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Ștefania Teodora Duca
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Alexandru Dan Costache
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iași, Romania
| | - Viviana Onofrei
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Ionuţ Tudorancea
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Ovidiu Mitu
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Minerva Codruța Bădescu
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Internal Medicine Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Lăcrămioara Ionela Șerban
- Department of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Irina Iuliana Costache
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
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14
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Liao R, Li Z, Wang Q, Lin H, Sun H. Revascularization of chronic total occlusion coronary artery and cardiac regeneration. Front Cardiovasc Med 2022; 9:940808. [PMID: 36093131 PMCID: PMC9455703 DOI: 10.3389/fcvm.2022.940808] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 08/05/2022] [Indexed: 11/13/2022] Open
Abstract
Coronary chronic total occlusion (CTO) contributes to the progression of heart failure in patients with ischemic cardiomyopathy. Randomized controlled trials demonstrated that percutaneous coronary intervention (PCI) for CTO significantly improves angina symptoms and quality of life but fails to reduce clinical events compared with optimal medical therapy. Even so, intervening physicians strongly support CTO-PCI. Cardiac regeneration therapy after CTO-PCI should be a promising approach to improving the prognosis of ischemic cardiomyopathy. However, the relationship between CTO revascularization and cardiac regeneration has rarely been studied, and experimental studies on cardiac regeneration usually employ rodent models with permanent ligation of the coronary artery rather than reopening of the occlusive artery. Limited early-stage clinical trials demonstrated that cell therapy for cardiac regeneration in ischemic cardiomyopathy reduces scar size, reverses cardiac remodeling, and promotes angiogenesis. This review focuses on the status quo of CTO-PCI in ischemic cardiomyopathy and the clinical prospect of cardiac regeneration in this setting.
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Affiliation(s)
- Ruoxi Liao
- Department of Clinical Medicine, Dalian Medical University, Dalian, China
| | - Zhihong Li
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qiancheng Wang
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hairuo Lin
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- *Correspondence: Hairuo Lin, ,
| | - Huijun Sun
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Huijun Sun,
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15
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Mehta C, Shah R, Yanamala N, Sengupta PP. Cardiovascular Imaging Databases: Building Machine Learning Algorithms for Regenerative Medicine. CURRENT STEM CELL REPORTS 2022. [DOI: 10.1007/s40778-022-00216-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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16
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Leancă SA, Crișu D, Petriș AO, Afrăsânie I, Genes A, Costache AD, Tesloianu DN, Costache II. Left Ventricular Remodeling after Myocardial Infarction: From Physiopathology to Treatment. Life (Basel) 2022; 12:1111. [PMID: 35892913 PMCID: PMC9332014 DOI: 10.3390/life12081111] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 12/11/2022] Open
Abstract
Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries and rapidly growing in developing countries. The most common cause of MI is the rupture of an atherosclerotic plaque with subsequent thrombotic occlusion in the coronary circulation. This causes cardiomyocyte death and myocardial necrosis, with subsequent inflammation and fibrosis. Current therapies aim to restore coronary flow by thrombus dissolution with pharmaceutical treatment and/or intravascular stent implantation and to counteract neurohormonal activation. Despite these therapies, the injury caused by myocardial ischemia leads to left ventricular remodeling; this process involves changes in cardiac geometry, dimension and function and eventually progression to heart failure (HF). This review describes the pathophysiological mechanism that leads to cardiac remodeling and the therapeutic strategies with a role in slowing the progression of remodeling and improving cardiac structure and function.
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Affiliation(s)
- Sabina Andreea Leancă
- Department of Cardiology, Emergency Clinical Hospital “Sf. Spiridon”, Bd. Independentei nr. 1, 700111 Iasi, Romania; (S.A.L.); (A.O.P.); (I.A.); (A.G.); (D.N.T.); (I.I.C.)
| | - Daniela Crișu
- Department of Cardiology, Emergency Clinical Hospital “Sf. Spiridon”, Bd. Independentei nr. 1, 700111 Iasi, Romania; (S.A.L.); (A.O.P.); (I.A.); (A.G.); (D.N.T.); (I.I.C.)
| | - Antoniu Octavian Petriș
- Department of Cardiology, Emergency Clinical Hospital “Sf. Spiridon”, Bd. Independentei nr. 1, 700111 Iasi, Romania; (S.A.L.); (A.O.P.); (I.A.); (A.G.); (D.N.T.); (I.I.C.)
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Str. University nr. 16, 700083 Iasi, Romania;
| | - Irina Afrăsânie
- Department of Cardiology, Emergency Clinical Hospital “Sf. Spiridon”, Bd. Independentei nr. 1, 700111 Iasi, Romania; (S.A.L.); (A.O.P.); (I.A.); (A.G.); (D.N.T.); (I.I.C.)
| | - Antonia Genes
- Department of Cardiology, Emergency Clinical Hospital “Sf. Spiridon”, Bd. Independentei nr. 1, 700111 Iasi, Romania; (S.A.L.); (A.O.P.); (I.A.); (A.G.); (D.N.T.); (I.I.C.)
| | - Alexandru Dan Costache
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Str. University nr. 16, 700083 Iasi, Romania;
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Dan Nicolae Tesloianu
- Department of Cardiology, Emergency Clinical Hospital “Sf. Spiridon”, Bd. Independentei nr. 1, 700111 Iasi, Romania; (S.A.L.); (A.O.P.); (I.A.); (A.G.); (D.N.T.); (I.I.C.)
| | - Irina Iuliana Costache
- Department of Cardiology, Emergency Clinical Hospital “Sf. Spiridon”, Bd. Independentei nr. 1, 700111 Iasi, Romania; (S.A.L.); (A.O.P.); (I.A.); (A.G.); (D.N.T.); (I.I.C.)
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Str. University nr. 16, 700083 Iasi, Romania;
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17
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Munderere R, Kim SH, Kim C, Park SH. The Progress of Stem Cell Therapy in Myocardial-Infarcted Heart Regeneration: Cell Sheet Technology. Tissue Eng Regen Med 2022; 19:969-986. [PMID: 35857259 DOI: 10.1007/s13770-022-00467-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 05/18/2022] [Accepted: 05/19/2022] [Indexed: 11/30/2022] Open
Abstract
Various tissues, including the heart, cornea, bone, esophagus, bladder and liver, have been vascularized using the cell sheet technique. It overcomes the limitations of existing techniques by allowing small layers of the cell sheet to generate capillaries on their own, and it can also be used to vascularize tissue-engineered transplants. Cell sheets eliminate the need for traditional tissue engineering procedures such as isolated cell injections and scaffold-based technologies, which have limited applicability. While cell sheet engineering can eliminate many of the drawbacks, there are still a few challenges that need to be addressed. The number of cell sheets that can be layered without triggering core ischemia or hypoxia is limited. Even when scaffold-based technologies are disregarded, strategies to tackle this problem remain a substantial impediment to the efficient regeneration of thick, living three-dimensional cell sheets. In this review, we summarize the cell sheet technology in myocardial infarcted tissue regeneration.
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Affiliation(s)
- Raissa Munderere
- Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, Republic of Korea.,The Center for Marine Integrated Biomedical Technology (BK21 PLUS), Pukyong National University, Busan, Republic of Korea
| | - Seon-Hwa Kim
- Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, Republic of Korea.,The Center for Marine Integrated Biomedical Technology (BK21 PLUS), Pukyong National University, Busan, Republic of Korea
| | - Changsu Kim
- Department of Orthopedics Surgery, Kosin University Gospel Hospital, Busan, Republic of Korea
| | - Sang-Hyug Park
- Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, Republic of Korea. .,The Center for Marine Integrated Biomedical Technology (BK21 PLUS), Pukyong National University, Busan, Republic of Korea. .,Major of Biomedical Engineering, Division of Smart Healthcare, College of Information Technology and Convergence, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan, 48513, Republic of Korea.
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18
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Gori T. Restenosis after Coronary Stent Implantation: Cellular Mechanisms and Potential of Endothelial Progenitor Cells (A Short Guide for the Interventional Cardiologist). Cells 2022; 11:cells11132094. [PMID: 35805178 PMCID: PMC9265311 DOI: 10.3390/cells11132094] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/26/2022] [Accepted: 06/28/2022] [Indexed: 02/05/2023] Open
Abstract
Coronary stents are among the most common therapies worldwide. Despite significant improvements in the biocompatibility of these devices throughout the last decades, they are prone, in as many as 10–20% of cases, to short- or long-term failure. In-stent restenosis is a multifactorial process with a complex and incompletely understood pathophysiology in which inflammatory reactions are of central importance. This review provides a short overview for the clinician on the cellular types responsible for restenosis with a focus on the role of endothelial progenitor cells. The mechanisms of restenosis are described, along with the cell-based attempts made to prevent it. While the focus of this review is principally clinical, experimental evidence provides some insight into the potential implications for prevention and therapy of coronary stent restenosis.
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Affiliation(s)
- Tommaso Gori
- German Center for Cardiac and Vascular Research (DZHK) Standort Rhein-Main, Department of Cardiology, University Medical Center Mainz, 55131 Mainz, Germany
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19
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Costa A, Pasquinelli G. Air Pollution Exposure Induces Vascular Injury and Hampers Endothelial Repair by Altering Progenitor and Stem Cells Functionality. Front Cell Dev Biol 2022; 10:897831. [PMID: 35712669 PMCID: PMC9197257 DOI: 10.3389/fcell.2022.897831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 04/20/2022] [Indexed: 11/13/2022] Open
Abstract
Extensive evidence indicates an association of air pollution exposure with an increased risk of cardiovascular disease (CVD) development. Fine particulate matter (PM) represents one of the main components of urban pollution, but the mechanisms by which it exerts adverse effects on cardiovascular system remain partially unknown and under investigation. The alteration of endothelial functions and inflammation are among the earliest pathophysiological impacts of environmental exposure on the cardiovascular system and represent critical mediators of PM-induced injury. In this context, endothelial stem/progenitor cells (EPCs) play an important role in vascular homeostasis, endothelial reparative capacity, and vasomotor functionality modulation. Several studies indicate the impairment of EPCs' vascular reparative capacity due to PM exposure. Since a central source of EPCs is bone marrow (BM), their number and function could be related to the population and functional status of stem cells (SCs) of this district. In this review, we provide an overview of the potential mechanisms by which PM exposure hinders vascular repair by the alteration of progenitor and stem cells' functionality.
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Affiliation(s)
- Alice Costa
- Laboratory of Clinical Pathology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
| | - Gianandrea Pasquinelli
- Laboratory of Clinical Pathology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
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20
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Current Status of Stem Cell Therapy in Heart Failure. Indian J Surg 2022. [DOI: 10.1007/s12262-022-03426-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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21
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Imam SS, Al-Abbasi FA, Hosawi S, Afzal M, Nadeem MS, Ghoneim MM, Alshehri S, Alzarea SI, Alquraini A, Gupta G, Kazmi I. Role of platelet rich plasma mediated repair and regeneration of cell in early stage of cardiac injury. Regen Ther 2022; 19:144-153. [PMID: 35229012 PMCID: PMC8856949 DOI: 10.1016/j.reth.2022.01.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/18/2022] [Accepted: 01/27/2022] [Indexed: 12/12/2022] Open
Abstract
Platelet-rich plasma (PRP) is a widely accepted treatment approach and has heightened the quality of care among physicians. PRP has been used over the last decade to boost clinical results of plastic therapies, periodontal surgery and intra-bony defects. According to certain research, elevated levels of PRP growth factors that could promote tissue repair and have the potential for PRP to be beneficial in regenerating processes that Maxillofacial and Oral Surgeons, Veterinary Officers, Athletic medicine specialists and Dermatologists have long admired. PRP is an autologous whole blood fraction that has a heavy amount of a variety of growth factors such as epidermal growth factor (EGF), Vascular Endothelial Growth Factor (VEGF), hepatocyte growth factor (HGF), fibroblast growth factors (FGFs), transforming growth factor beta-1 (TGF-b), insulin-like growth factor-I (IGF-I) and platelet-derived growth factor (PDGF) which can facilitate repair and regeneration. Moreover, a clinical trial of PRP in severe angina patients has shown its excellent safety profile. However, PRP is a very complex biological substance with an array of active biomolecules, its functions are yet to be fully clarified. In-addition, there was insufficient work assessing possible cardiovascular tissue benefits from PRP. Thus, it still remains necessary to identify the most clinically important cardiovascular applications and further research in clinical scenario need to be validated.
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Key Words
- ADMSC, adipose-derived mesenchymal stem cells
- BMSCs, bone marrow-derived mesenchymal stem cells
- Cardiac injury
- Cell repair and regeneration
- EGF, epidermal growth factor
- FDPs, fibrin degradation products
- FGFs, fibroblast growth factors
- HGF, hepatocyte growth factor
- IGF-I, insulin-like growth factor-I
- IRI, ischemic reperfusion injury
- ISO, Isoproterenol
- LP-PRP, leukocyte-poor PRP
- LR-PRP, leukocyte-rich PRP
- MH, Manuka honey
- MI, myocardial infarction
- MRI, magnetic resonance imaging
- P-PRF, pure platelet-rich fibrin
- PDGF, platelet-derived growth factor
- PRP, platelet-rich plasma
- Platelet-rich plasma
- ROS, reactive oxygen species
- TGF-b, transforming growth factor beta
- VEGF, vascular endothelial growth factor
- nsPEF, nanosecond pulsed electric fields
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Affiliation(s)
- Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Fahad A. Al-Abbasi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Salman Hosawi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Muhammad Afzal
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf-72341, Saudi Arabia
| | - Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Mohammed M. Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Sami I. Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf-72341, Saudi Arabia
| | - Ali Alquraini
- Department of Pharmaceutical Chemistry, Faculty of Clinical Pharmacy, Al Baha University, Al Baha 65779, Saudi Arabia
| | - Gaurav Gupta
- Department of Pharmacology, School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
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22
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Wu X, Darlington DN, Christy BA, Liu B, Keesee JD, Salgado CL, Bynum JA, Cap AP. Intravenous administration of mesenchymal stromal cells leads to a dose-dependent coagulopathy and is unable to attenuate acute traumatic coagulopathy in rats. J Trauma Acute Care Surg 2022; 92:542-552. [PMID: 34797814 PMCID: PMC8860226 DOI: 10.1097/ta.0000000000003476] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 11/01/2021] [Accepted: 11/06/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Mesenchymal stromal cells (MSCs) express surface tissue factor (TF), which may affect hemostasis and detract from therapeutic outcomes of MSCs if administered intravenously. In this study, we determine a safe dose of MSCs for intravenous (IV) administration and further demonstrate the impact of IV-MSC on acute traumatic coagulopathy (ATC) in rats. METHODS Tissue factor expression of rat bone marrow-derived mesenchymal stromal cell (BMSC) or adipose-derived mesenchymal stromal cell (AMSC) was detected by immunohistochemistry and enzyme-linked immunosorbent assay. The coagulation properties were measured in MSC-treated rat whole blood, and blood samples were collected from rats after IV administration of MSCs. Acute traumatic coagulopathy rats underwent polytrauma and 40% hemorrhage, followed by IV administration of 5 or 10 million/kg BMSCs (BMSC-5, BMSC-10), or vehicle at 1 hour after trauma. RESULTS Rat MSCs expressed TF, and incubation of rat BMSCs or AMSCs with whole blood in vitro led to a significantly shortened clotting time. However, a dose-dependent prolongation of prothrombin time with reduction in platelet counts and fibrinogen was found in healthy rat treated with IV-MSCs. Bone marrow-derived mesenchymal stromal cells at 5 million/kg or less led to minimal effect on hemostasis. Mesenchymal stromal cells were not found in circulation but in the lungs after IV administration regardless of the dosage. Acute traumatic coagulopathy with prolonged prothrombin time was not significantly affected by 5 or 10 million/kg BMSCs. Intravenous administration of 10 million/kg BMSCs led to significantly lower fibrinogen and platelet counts, while significantly higher levels of lactate, wet/dry weight ratio, and leukocyte infiltration in the lung were present compared with BMSC-5 or vehicle. No differences were seen in immune or inflammatory profiles with BMSC treatment in ATC rats, at least in the acute timeframe. CONCLUSION Intravenous administration of MSCs leads to a risk of coagulopathy associated with a dose-dependent reduction in platelet counts and fibrinogen and is incapable of restoring hemostasis of rats with ATC after polytrauma and hemorrhagic shock.
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Mathur A, Sim DS, Choudry F, Veerapen J, Colicchia M, Turlejski T, Hussain M, Hamshere S, Locca D, Rakhit R, Crake T, Kastrup J, Agrawal S, Jones DA, Martin J. Five‐year follow‐up of intracoronary autologous cell therapy in acute myocardial infarction: the REGENERATE‐AMI trial. ESC Heart Fail 2022; 9:1152-1159. [PMID: 35043578 PMCID: PMC8934988 DOI: 10.1002/ehf2.13786] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 10/18/2021] [Accepted: 12/13/2021] [Indexed: 12/22/2022] Open
Abstract
Aims The long‐term outcomes of the intracoronary delivery of autologous bone marrow‐derived cells (BMCs) after acute myocardial infarction are not well established. Following the promising 1 year results of the REGENERATE‐AMI trial (despite it not achieving its primary endpoint), this paper presents the analysis of the 5 year clinical outcomes of these acute myocardial infarction patients who were treated with an early intracoronary autologous BMC infusion or placebo. Methods and results A 5 year follow‐up of major adverse cardiac events (defined as the composite of all‐cause death, recurrent myocardial infarction, and all coronary revascularization) and of rehospitalization for heart failure was completed in 85 patients (BMC n = 46 and placebo n = 39). The incidence of major adverse cardiac events was similar between the BMC‐treated patients and the placebo group (26.1% vs. 18.0%, P = 0.41). There were no cases of cardiac death in either group, but an increase in non‐cardiac death was seen in the BMC group (6.5% vs. 0%, P = 0.11). The rates of recurrent myocardial infarction and repeat revascularization were similar between the two groups. There were no cases of rehospitalization for heart failure in either group. Conclusion This 5 year follow‐up analysis of the REGENERATE‐AMI trial did not show an improvement in clinical outcomes for patients treated with cell therapy. This contrasts with the 1 year results which showed improvements in the surrogate outcome measures of ejection fraction and myocardial salvage index.
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Affiliation(s)
- Anthony Mathur
- Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute Queen Mary University of London London UK
- Department of Cardiology Barts Heart Centre, Barts Health NHS Trust London UK
| | - Doo Sun Sim
- Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute Queen Mary University of London London UK
- Department of Cardiovascular Medicine Chonnam National University Hospital, Chonnam National University School of Medicine Gwangju Korea
| | - Fizzah Choudry
- Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute Queen Mary University of London London UK
- Department of Cardiology Barts Heart Centre, Barts Health NHS Trust London UK
| | - Jessry Veerapen
- Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute Queen Mary University of London London UK
- Department of Cardiology Barts Heart Centre, Barts Health NHS Trust London UK
| | - Martina Colicchia
- Department of Cardiology Barts Heart Centre, Barts Health NHS Trust London UK
| | - Tymoteusz Turlejski
- Department of Cardiology Barts Heart Centre, Barts Health NHS Trust London UK
| | - Mohsin Hussain
- Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute Queen Mary University of London London UK
- Department of Cardiology Barts Heart Centre, Barts Health NHS Trust London UK
| | - Stephen Hamshere
- Department of Cardiology Barts Heart Centre, Barts Health NHS Trust London UK
| | - Didier Locca
- Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute Queen Mary University of London London UK
- École Polytechnique Fédérale de Lausanne Lausanne Switzerland
| | - Roby Rakhit
- Department of Cardiology The Royal Free Hospital, Royal Free London Foundation Trust London UK
| | - Tom Crake
- Department of Cardiology Barts Heart Centre, Barts Health NHS Trust London UK
| | - Jens Kastrup
- Rigshospitalet and University of Copenhagen Copenhagen Denmark
| | - Samir Agrawal
- Haemato‐Oncology, Barts Health NHS Trust & Immunobiology, Blizard Institute Queen Mary University of London London UK
| | - Daniel A. Jones
- Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute Queen Mary University of London London UK
- Department of Cardiology Barts Heart Centre, Barts Health NHS Trust London UK
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Chen W, Li X, Chen Z, Hao W, Yao P, Li M, Liu K, Hu H, Wang S, Wang Y. A comprehensive quality analysis of randomized controlled clinical trials of Asian ginseng and American ginseng based on the CONSORT guideline. J Ginseng Res 2022; 46:71-78. [PMID: 35035241 PMCID: PMC8753457 DOI: 10.1016/j.jgr.2021.05.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/05/2021] [Accepted: 05/10/2021] [Indexed: 12/21/2022] Open
Abstract
Ginseng is an international herb that has been used for thousands of years. Two species most commonly applied and investigated in the ginseng family are Asian ginseng and American ginseng. The number of randomized controlled clinical trials (RCTs) has conspicuously increased, driven by the rapid development of ginseng. However, the reporting of RCT items of ginseng is deficient because of different trial designs and reporting formats, which is a challenge for researchers who are looking for the data with high quality and reliability. Thus, this study focused on providing an extensive analysis of these two species and examined the quality of the RCTs, based on the Consolidated Standards of Reporting Trials (CONSORT) guideline. Ninety-one RCTs conducted from 1980 to 2019 that were related to Asian ginseng and American ginseng used singly met our inclusion criteria. We found that the reporting quality of the two species has improved during the past 40 years. Publication date and sample size were significantly associated with the reporting quality. Rigorous RCTs designed for the species of ginseng are warranted, which can shed light on product research and development of ginseng in the future.
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Affiliation(s)
- Weijie Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
| | - Xiuzhu Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
| | - Zhejie Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
| | - Wei Hao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
| | - Peifen Yao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
| | - Meng Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
| | - Kunmeng Liu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
| | - Hao Hu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
| | - Shengpeng Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
| | - Yitao Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
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Goonoo N. Tunable Biomaterials for Myocardial Tissue Regeneration: Promising New Strategies for Advanced Biointerface Control and Improved Therapeutic Outcomes. Biomater Sci 2022; 10:1626-1646. [DOI: 10.1039/d1bm01641e] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Following myocardial infarction (MI) and the natural healing process, the cardiac mechanostructure changes significantly leading to reduced contractile ability and putting additional pressure on the heart muscle thereby increasing the...
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Ma S, Yan J, Chen L, Zhu Y, Chen K, Zheng C, Shen M, Liao Y. A Bibliometric and Visualized Analysis of Cardiac Regeneration Over a 20-Year Period. Front Cardiovasc Med 2021; 8:789503. [PMID: 34966800 PMCID: PMC8710530 DOI: 10.3389/fcvm.2021.789503] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/01/2021] [Indexed: 12/16/2022] Open
Abstract
Background: Recent research has suggested that cardiac regeneration may have the widely applicable potential of treating heart failure (HF). A comprehensive understanding of the development status of this field is conducive to its development. However, no bibliometric analysis has summarized this field properly. We aimed to analyze cardiac regeneration-related literature over 20 years and provide valuable insights. Methods: Publications were collected from the Web of Science Core Collection (WoSCC). Microsoft Excel, VOSviewer, CiteSpace, and alluvial generator were used to analyze and present the data. Results: The collected 11,700 publications showed an annually increasing trend. The United States and Harvard University were the leading force among all the countries and institutions. The majority of articles were published in Circulation Research, and Circulation was the most co-cited journal. According to co-citation analysis, burst detection and alluvial flow map, cardiomyocyte proliferation, stem cells, such as first-and second-generation, extracellular vesicles especially exosomes, direct cardiac reprogramming, macrophages, microRNAs, and inflammation have become more and more popular recently. Conclusions: Cardiac regeneration remains a research hotspot and develops rapidly. How to modify cardiac regeneration endogenously and exogenously may still be the hotspot in the future and should be discussed more deeply.
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Affiliation(s)
- Siyuan Ma
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Department of Cardiology, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junyu Yan
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Department of Cardiology, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lu Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Department of Cardiology, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yingqi Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Department of Cardiology, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Kaitong Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Department of Cardiology, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Cankun Zheng
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Department of Cardiology, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Mengjia Shen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Department of Cardiology, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yulin Liao
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Department of Cardiology, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Yamada Y, Minatoguchi S, Kanamori H, Mikami A, Okura H, Dezawa M, Minatoguchi S. Stem cell therapy for acute myocardial infarction - focusing on the comparison between Muse cells and mesenchymal stem cells. J Cardiol 2021; 80:80-87. [PMID: 34924234 DOI: 10.1016/j.jjcc.2021.10.030] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 10/20/2021] [Indexed: 02/08/2023]
Abstract
Rapid percutaneous coronary intervention for acute myocardial infarction (AMI) reduces acute mortality, but there is an urgent need for treatment of left ventricular dysfunction and remodeling after AMI to improve the prognosis. The myocardium itself does not have a high regenerative capacity, and it is important to minimize the loss of cardiomyocytes and maintain the cardiac function after AMI. To overcome these problems, attention has been focused on myocardial regeneration therapy using cells derived from bone marrow. The clinical use of bone marrow stem cells is considered to have low safety concerns based on the experience of using bone marrow transplantation for blood diseases in clinical practice. It has been reported that bone marrow mononuclear cells (BM-MNC) and mesenchymal stem cells (BM-MSC) differentiate into cardiomyocytes both in vitro and in vivo, and they have been considered a promising source for stem cell therapy. To prevent heart failure after human AMI, studies have been conducted to regenerate myocardial tissue by transplanting bone marrow stem cells, such as BM-MSCs and BM-MNCs. Therapies using those cells have been administered to animal models of AMI, and were effective to some extent, but the effect in clinical trials was limited. Recently, it was reported that multilineage-differentiating stress enduring cells (Muse cells), which are endogenous pluripotent stem cells obtainable from various tissues including the bone marrow, more markedly reduced the myocardial infarct size and improved the cardiac function via regeneration of cardiomyocytes and vessels and paracrine effects compared with BM-MSCs. Here, we describe stem cell therapies using conventional BM-MNCs and BM-MSCs, and Muse cells which have potential for clinical use for the treatment of AMI.
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Affiliation(s)
- Yoshihisa Yamada
- Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
| | - Shingo Minatoguchi
- Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hiromitsu Kanamori
- Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Atsushi Mikami
- Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hiroyuki Okura
- Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Mari Dezawa
- Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Miyagi, Japan
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Potential of Bone-Marrow-Derived Mesenchymal Stem Cells for Maxillofacial and Periodontal Regeneration: A Narrative Review. Int J Dent 2021; 2021:4759492. [PMID: 34795761 PMCID: PMC8594991 DOI: 10.1155/2021/4759492] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 09/19/2021] [Accepted: 10/25/2021] [Indexed: 12/11/2022] Open
Abstract
Bone-marrow-derived mesenchymal stem cells (BM-MSCs) are one of the most widely studied postnatal stem cell populations and are considered to utilize more frequently in cell-based therapy and cancer. These types of stem cells can undergo multilineage differentiation including blood cells, cardiac cells, and osteogenic cells differentiation, thus providing an alternative source of mesenchymal stem cells (MSCs) for tissue engineering and personalized medicine. Despite the ability to reprogram human adult somatic cells to induced pluripotent stem cells (iPSCs) in culture which provided a great opportunity and opened the new door for establishing the in vitro disease modeling and generating an unlimited source for cell base therapy, using MSCs for regeneration purposes still have a great chance to cure diseases. In this review, we discuss the important issues in MSCs biology including the origin and functions of MSCs and their application for craniofacial and periodontal tissue regeneration, discuss the potential and clinical applications of this type of stem cells in differentiation to maxillofacial bone and cartilage in vitro, and address important future hopes and challenges in this field.
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Pluripotent stem cell-derived mesenchymal stromal cells improve cardiac function and vascularity after myocardial infarction. Cytotherapy 2021; 23:1074-1084. [PMID: 34588150 DOI: 10.1016/j.jcyt.2021.07.016] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 07/27/2021] [Accepted: 07/28/2021] [Indexed: 01/10/2023]
Abstract
BACKGROUND AIMS Mesenchymal stromal cells (MSCs) have been shown to improve cardiac function after injury and are the subject of ongoing clinical trials. In this study, the authors tested the cardiac regenerative potential of an induced pluripotent stem cell-derived MSC (iPSC-MSC) population (Cymerus MSCs) in a rat model of myocardial ischemia-reperfusion (I/R). Furthermore, the authors compared this efficacy with bone marrow-derived MSCs (BM-MSCs), which are the predominant cell type in clinical trials. METHODS Four days after myocardial I/R injury, rats were randomly assigned to (i) a Cymerus MSC group (n = 15), (ii) a BM-MSC group (n = 15) or (iii) a vehicle control group (n = 14). For cell-treated animals, a total of 5 × 106 cells were injected at three sites within the infarcted left ventricular (LV) wall. RESULTS One month after cell transplantation, Cymerus MSCs improved LV function (assessed by echocardiography) compared with vehicle and BM-MSCs. Interestingly, Cymerus MSCs enhanced angiogenesis without sustained engraftment or significant impact on infarct scar size. Suggesting safety, Cymerus MSCs had no effect on inducible tachycardia or the ventricular scar heterogeneity that provides a substrate for cardiac re-entrant circuits. CONCLUSIONS The authors here demonstrate that intra-myocardial administration of iPSC-MSCs (Cymerus MSCs) provide better therapeutic effects compared with conventional BM-MSCs in a rodent model of myocardial I/R. Because of its manufacturing scalability, iPSC-MSC therapy offers an exciting opportunity for an "off-the-shelf" stem cell therapy for cardiac repair.
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Blume GG, Machado-Junior PAB, Simeoni RB, Bertinato GP, Tonial MS, Nagashima S, Pinho RA, de Noronha L, Olandoski M, de Carvalho KAT, Francisco JC, Guarita-Souza LC. Bone-Marrow Stem Cells and Acellular Human Amniotic Membrane in a Rat Model of Heart Failure. Life (Basel) 2021; 11:958. [PMID: 34575107 PMCID: PMC8471644 DOI: 10.3390/life11090958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 09/07/2021] [Accepted: 09/09/2021] [Indexed: 11/17/2022] Open
Abstract
Myocardial infarction (MI) remains the leading cause of cardiovascular death worldwide and a major cause of heart failure. Recent studies have suggested that cell-based therapies with bone marrow stem cells (BMSC) and human amniotic membrane (hAM) would recover the ventricular function after MI; however, the mechanisms underlying these effects are still controversial. Herein, we aimed to compare the effects of BMSC and hAM in a rat model of heart failure. MI was induced through coronary occlusion, and animals with an ejection fraction (EF) < 50% were included and randomized into three groups: control, BMSC, and hAM. The BMSC and hAM groups were implanted on the anterior ventricular wall seven days after MI, and a new echocardiographic analysis was performed on the 30th day, followed by euthanasia. The echocardiographic results after 30 days showed significant improvements on EF and left-ventricular end-sistolic and end-diastolic volumes in both BMSC and hAM groups, without significant benefits in the control group. New blood vessels, desmine-positive cells and connexin-43 expression were also elevated in both BMSC and hAM groups. These results suggest a recovery of global cardiac function with the therapeutic use of both BMSC and hAM, associated with angiogenesis and cardiomyocyte regeneration after 30 days.
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Affiliation(s)
- Gustavo Gavazzoni Blume
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; (P.A.B.M.-J.); (R.B.S.); (G.P.B.); (M.S.T.); (S.N.); (L.d.N.); (M.O.); (L.C.G.-S.)
| | - Paulo André Bispo Machado-Junior
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; (P.A.B.M.-J.); (R.B.S.); (G.P.B.); (M.S.T.); (S.N.); (L.d.N.); (M.O.); (L.C.G.-S.)
| | - Rossana Baggio Simeoni
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; (P.A.B.M.-J.); (R.B.S.); (G.P.B.); (M.S.T.); (S.N.); (L.d.N.); (M.O.); (L.C.G.-S.)
| | - Giovana Paludo Bertinato
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; (P.A.B.M.-J.); (R.B.S.); (G.P.B.); (M.S.T.); (S.N.); (L.d.N.); (M.O.); (L.C.G.-S.)
| | - Murilo Sgarbossa Tonial
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; (P.A.B.M.-J.); (R.B.S.); (G.P.B.); (M.S.T.); (S.N.); (L.d.N.); (M.O.); (L.C.G.-S.)
| | - Seigo Nagashima
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; (P.A.B.M.-J.); (R.B.S.); (G.P.B.); (M.S.T.); (S.N.); (L.d.N.); (M.O.); (L.C.G.-S.)
| | - Ricardo Aurino Pinho
- Laboratory of Exercise Biochemistry in Health, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil;
| | - Lucia de Noronha
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; (P.A.B.M.-J.); (R.B.S.); (G.P.B.); (M.S.T.); (S.N.); (L.d.N.); (M.O.); (L.C.G.-S.)
| | - Marcia Olandoski
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; (P.A.B.M.-J.); (R.B.S.); (G.P.B.); (M.S.T.); (S.N.); (L.d.N.); (M.O.); (L.C.G.-S.)
| | - Katherine Athayde Teixeira de Carvalho
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba 80215-901, Brazil; (K.A.T.d.C.); (J.C.F.)
| | - Julio Cesar Francisco
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba 80215-901, Brazil; (K.A.T.d.C.); (J.C.F.)
| | - Luiz Cesar Guarita-Souza
- Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; (P.A.B.M.-J.); (R.B.S.); (G.P.B.); (M.S.T.); (S.N.); (L.d.N.); (M.O.); (L.C.G.-S.)
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Narasimhan B, Narasimhan H, Lorente-Ros M, Romeo FJ, Bhatia K, Aronow WS. Therapeutic angiogenesis in coronary artery disease: a review of mechanisms and current approaches. Expert Opin Investig Drugs 2021; 30:947-963. [PMID: 34346802 DOI: 10.1080/13543784.2021.1964471] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 08/02/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Despite tremendous advances, the shortcomings of current therapies for coronary disease are evidenced by the fact that it remains the leading cause of death in many parts of the world. There is hence a drive to develop novel therapies to tackle this disease. Therapeutic approaches to coronary angiogenesis have long been an area of interest in lieu of its incredible, albeit unrealized potential. AREAS COVERED This paper offers an overview of mechanisms of native angiogenesis and a description of angiogenic growth factors. It progresses to outline the advances in gene and stem cell therapy and provides a brief description of other investigational approaches to promote angiogenesis. Finally, the hurdles and limitations unique to this particular area of study are discussed. EXPERT OPINION An effective, sustained, and safe therapeutic option for angiogenesis truly could be the paradigm shift for cardiovascular medicine. Unfortunately, clinically meaningful therapeutic options remain elusive because promising animal studies have not been replicated in human trials. The sheer complexity of this process means that numerous major hurdles remain before therapeutic angiogenesis truly makes its way from the bench to the bedside.
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Affiliation(s)
- Bharat Narasimhan
- Department Of Medicine, Mount Sinai St.Lukes-Roosevelt, Icahn School Of Medicine At Mount Sinai, New York, NY, USA
| | | | - Marta Lorente-Ros
- Department Of Medicine, Mount Sinai St.Lukes-Roosevelt, Icahn School Of Medicine At Mount Sinai, New York, NY, USA
| | - Francisco Jose Romeo
- Department Of Medicine, Mount Sinai St.Lukes-Roosevelt, Icahn School Of Medicine At Mount Sinai, New York, NY, USA
| | - Kirtipal Bhatia
- Department Of Medicine, Mount Sinai St.Lukes-Roosevelt, Icahn School Of Medicine At Mount Sinai, New York, NY, USA
| | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical Center/New York Medical College, Valhalla, NY, USA
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Hemalatha T, Aarthy M, Pandurangan S, Kamini NR, Ayyadurai N. A deep dive into the darning effects of biomaterials in infarct myocardium: current advances and future perspectives. Heart Fail Rev 2021; 27:1443-1467. [PMID: 34342769 DOI: 10.1007/s10741-021-10144-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/07/2021] [Indexed: 12/21/2022]
Abstract
Myocardial infarction (MI) occurs due to the obstruction of coronary arteries, a major crux that restricts blood flow and thereby oxygen to the distal part of the myocardium, leading to loss of cardiomyocytes and eventually, if left untreated, leads to heart failure. MI, a potent cardiovascular disorder, requires intense therapeutic interventions and thereby presents towering challenges. Despite the concerted efforts, the treatment strategies for MI are still demanding, which has paved the way for the genesis of biomaterial applications. Biomaterials exhibit immense potentials for cardiac repair and regeneration, wherein they act as extracellular matrix replacing scaffolds or as delivery vehicles for stem cells, protein, plasmids, etc. This review concentrates on natural, synthetic, and hybrid biomaterials; their function; and interaction with the body, mechanisms of repair by which they are able to improve cardiac function in a MI milieu. We also provide focus on future perspectives that need attention. The cognizance provided by the research results certainly indicates that biomaterials could revolutionize the treatment paradigms for MI with a positive impact on clinical translation.
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Affiliation(s)
- Thiagarajan Hemalatha
- Department of Biochemistry and Biotechnology, CSIR- Central Leather Research Institute, Chennai, 600020, India
| | - Mayilvahanan Aarthy
- Department of Biochemistry and Biotechnology, CSIR- Central Leather Research Institute, Chennai, 600020, India
| | - Suryalakshmi Pandurangan
- Department of Biochemistry and Biotechnology, CSIR- Central Leather Research Institute, Chennai, 600020, India
| | - Numbi Ramudu Kamini
- Department of Biochemistry and Biotechnology, CSIR- Central Leather Research Institute, Chennai, 600020, India
| | - Niraikulam Ayyadurai
- Department of Biochemistry and Biotechnology, CSIR- Central Leather Research Institute, Chennai, 600020, India.
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33
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Vilahur G, Nguyen PH, Badimon L. Impact of Diabetes Mellitus on the Potential of Autologous Stem Cells and Stem Cell-Derived Microvesicles to Repair the Ischemic Heart. Cardiovasc Drugs Ther 2021; 36:933-949. [PMID: 34251593 DOI: 10.1007/s10557-021-07208-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/25/2021] [Indexed: 10/20/2022]
Abstract
Ischemic heart disease remains the leading cause of morbidity and mortality worldwide. Despite the advances in medical management and catheter-based therapy, mortality remains high, as does the risk of developing heart failure. Regenerative therapies have been widely used as an alternative option to repair the damaged heart mainly because of their paracrine-related beneficial effects. Although cell-based therapy has been demonstrated as feasible and safe, randomized controlled trials and meta-analyses show little consistent benefit from treatments with adult-derived stem cells. Mounting evidence from our group and others supports that cardiovascular risk factors and comorbidities impair stem cell potential thus hampering their autologous use. This review aims to better understand the influence of diabetes on stem cell potential. For this purpose, we will first discuss the most recent advances in the mechanistic understanding of the effects of diabetes on stem cell phenotype, function, and molecular fingerprint to further elaborate on diabetes-induced alterations in stem cell extracellular vesicle profile. Although we acknowledge that multiple sources of stem or progenitor cells are used for regenerative purposes, we will focus on bone marrow hematopoietic stem/progenitor cells, mesenchymal stem cells residing in the bone marrow, and adipose tissue and briefly discuss endothelial colony-forming cells.
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Affiliation(s)
- Gemma Vilahur
- Cardiovascular-Program ICCC, IR-Hospital Santa Creu I Sant Pau, IIB Sant Pau, C/Sant Antoni Mª Claret 167, 08025, Barcelona, Spain.,Ciber CV - ISCIII, Madrid, Spain
| | - Phuong Hue Nguyen
- Cardiovascular-Program ICCC, IR-Hospital Santa Creu I Sant Pau, IIB Sant Pau, C/Sant Antoni Mª Claret 167, 08025, Barcelona, Spain
| | - Lina Badimon
- Cardiovascular-Program ICCC, IR-Hospital Santa Creu I Sant Pau, IIB Sant Pau, C/Sant Antoni Mª Claret 167, 08025, Barcelona, Spain. .,Ciber CV - ISCIII, Madrid, Spain. .,Cardiovascular Research Chair UAB, Barcelona, Spain.
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34
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Carbone RG, Monselise A, Bottino G, Negrini S, Puppo F. Stem cells therapy in acute myocardial infarction: a new era? Clin Exp Med 2021; 21:231-237. [PMID: 33484381 PMCID: PMC8053645 DOI: 10.1007/s10238-021-00682-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 01/04/2021] [Indexed: 12/12/2022]
Abstract
Stem cells transplantation after acute myocardial infarction (AMI) has been claimed to restore cardiac function. However, this therapy is still restricted to experimental studies and clinical trials. Early un-blinded studies suggested a benefit from stem cell therapy following AMI. More recent blinded randomized trials have produced mixed results and, notably, the last largest pan-European clinical trial showed the inconclusive results. Furthermore, mechanisms of potential benefit remain uncertain. This review analytically evaluates 34 blinded and un-blinded clinical trials comprising 3142 patients and is aimed to: (1) identify the pros and cons of stem cell therapy up to a 6-month follow-up after AMI comparing benefit or no effectiveness reported in clinical trials; (2) provide useful information for planning future clinical programs of cardiac stem cell therapy.
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Affiliation(s)
- R G Carbone
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | | | - G Bottino
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - S Negrini
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - F Puppo
- Department of Internal Medicine, University of Genoa, Genoa, Italy.
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35
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Campos de Carvalho AC, Kasai-Brunswick TH, Bastos Carvalho A. Cell-Based Therapies for Heart Failure. Front Pharmacol 2021; 12:641116. [PMID: 33912054 PMCID: PMC8072383 DOI: 10.3389/fphar.2021.641116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Accepted: 02/11/2021] [Indexed: 02/05/2023] Open
Abstract
Heart failure has reached epidemic proportions with the advances in cardiovascular therapies for ischemic heart diseases and the progressive aging of the world population. Efficient pharmacological therapies are available for treating heart failure, but unfortunately, even with optimized therapy, prognosis is often poor. Their last therapeutic option is, therefore, a heart transplantation with limited organ supply and complications related to immunosuppression. In this setting, cell therapies have emerged as an alternative. Many clinical trials have now been performed using different cell types and injection routes. In this perspective, we will analyze the results of such trials and discuss future perspectives for cell therapies as an efficacious treatment of heart failure.
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Affiliation(s)
- Antonio Carlos Campos de Carvalho
- Laboratory of Cellular and Molecular Cardiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- National Center of Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- National Institute of Science and Technology in Regenerative Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Tais H. Kasai-Brunswick
- National Center of Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- National Institute of Science and Technology in Regenerative Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Adriana Bastos Carvalho
- Laboratory of Cellular and Molecular Cardiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- National Institute of Science and Technology in Regenerative Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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36
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Yan M, Sun S, Xu K, Huang X, Dou L, Pang J, Tang W, Shen T, Li J. Cardiac Aging: From Basic Research to Therapeutics. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:9570325. [PMID: 33777324 PMCID: PMC7969106 DOI: 10.1155/2021/9570325] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 02/07/2021] [Accepted: 02/11/2021] [Indexed: 01/12/2023]
Abstract
With research progress on longevity, we have gradually recognized that cardiac aging causes changes in heart structure and function, including progressive myocardial remodeling, left ventricular hypertrophy, and decreases in systolic and diastolic function. Elucidating the regulatory mechanisms of cardiac aging is a great challenge for biologists and physicians worldwide. In this review, we discuss several key molecular mechanisms of cardiac aging and possible prevention and treatment methods developed in recent years. Insights into the process and mechanism of cardiac aging are necessary to protect against age-related diseases, extend lifespan, and reduce the increasing burden of cardiovascular disease in elderly individuals. We believe that research on cardiac aging is entering a new era of unique significance for the progress of clinical medicine and social welfare.
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Affiliation(s)
- Mingjing Yan
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
- Peking University Fifth School of Clinical Medicine, Beijing 100730, China
| | - Shenghui Sun
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Kun Xu
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Xiuqing Huang
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Lin Dou
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Jing Pang
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Weiqing Tang
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Tao Shen
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
- Peking University Fifth School of Clinical Medicine, Beijing 100730, China
| | - Jian Li
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
- Peking University Fifth School of Clinical Medicine, Beijing 100730, China
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37
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Bui TVA, Hwang JW, Lee JH, Park HJ, Ban K. Challenges and Limitations of Strategies to Promote Therapeutic Potential of Human Mesenchymal Stem Cells for Cell-Based Cardiac Repair. Korean Circ J 2021; 51:97-113. [PMID: 33525065 PMCID: PMC7853896 DOI: 10.4070/kcj.2020.0518] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 12/16/2020] [Indexed: 12/18/2022] Open
Abstract
Mesenchymal stem cells (MSCs) represent a population of adult stem cells residing in many tissues, mainly bone marrow, adipose tissue, and umbilical cord. Due to the safety and availability of standard procedures and protocols for isolation, culturing, and characterization of these cells, MSCs have emerged as one of the most promising sources for cell-based cardiac regenerative therapy. Once transplanted into a damaged heart, MSCs release paracrine factors that nurture the injured area, prevent further adverse cardiac remodeling, and mediate tissue repair along with vasculature. Numerous preclinical studies applying MSCs have provided significant benefits following myocardial infarction. Despite promising results from preclinical studies using animal models, MSCs are not up to the mark for human clinical trials. As a result, various approaches have been considered to promote the therapeutic potency of MSCs, such as genetic engineering, physical treatments, growth factor, and pharmacological agents. Each strategy has targeted one or multi-potentials of MSCs. In this review, we will describe diverse approaches that have been developed to promote the therapeutic potential of MSCs for cardiac regenerative therapy. Particularly, we will discuss major characteristics of individual strategy to enhance therapeutic efficacy of MSCs including scientific principles, advantages, limitations, and improving factors. This article also will briefly introduce recent novel approaches that MSCs enhanced therapeutic potentials of other cells for cardiac repair.
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Affiliation(s)
- Thi Van Anh Bui
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China
| | - Ji Won Hwang
- Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Korea.,Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Jung Hoon Lee
- Department of Chemistry, City University of Hong Kong, Hong Kong SAR, China
| | - Hun Jun Park
- Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Korea.,Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.,Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
| | - Kiwon Ban
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China.
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38
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Berezin AE, Berezin AA. Stem-Cell-Based Cardiac Regeneration: Is There a Place For Optimism in the Future? Stem Cells 2021. [DOI: 10.1007/978-3-030-77052-5_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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39
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Castillo-Díaz LA, Ruiz-Pacheco JA, Elsawy MA, Reyes-Martínez JE, Enríquez-Rodríguez AI. Self-Assembling Peptides as an Emerging Platform for the Treatment of Metabolic Syndrome. Int J Nanomedicine 2020; 15:10349-10370. [PMID: 33376325 PMCID: PMC7762440 DOI: 10.2147/ijn.s278189] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/21/2020] [Indexed: 12/14/2022] Open
Abstract
Metabolic syndrome comprises a cluster of comorbidities that represent a major risk of developing chronic diseases, such as type II diabetes, cardiovascular diseases, and stroke. Alarmingly, metabolic syndrome reaches epidemic proportions worldwide. Today, lifestyle changes and multiple drug-based therapies represent the gold standard to address metabolic syndrome. However, such approaches face two major limitations: complicated drug therapeutic regimes, which in most cases could lead to patient incompliance, and limited drug efficacy. This has encouraged scientists to search for novel routes to deal with metabolic syndrome and related diseases. Within such approaches, self-assembled peptide formulations have emerged as a promising alternative for treating metabolic syndrome. In particular, self-assembled peptide hydrogels, either as acellular or cell-load three-dimensional scaffoldings have reached significant relevance in the biomedical field to prevent and restore euglycemia, as well as for controlling cardiovascular diseases and obesity. This has been possible thanks to the physicochemical tunability of peptides, which are developed from a chemical toolbox of versatile amino acids enabling flexibility of designing a wide range of self-assembled/co-assembled nanostructures forming biocompatible viscoelastic hydrogels. Peptide hydrogels can be combined with several biological entities, such as extracellular matrix proteins, drugs or cells, forming functional biologics with therapeutic ability for treatment of metabolic syndrome-comorbidities. Additionally, self-assembly peptides combine safety, tolerability, and effectivity attributes; by this presenting a promising platform for the development of novel pharmaceuticals capable of addressing unmet therapeutic needs for diabetes, cardiovascular disorders and obesity. In this review, recent advances in developing self-assembly peptide nanostructures tailored for improving treatment of metabolic syndrome and related diseases will be discussed from basic research to preclinical research studies. Challenges facing the development of approved medicinal products based on self-assembling peptide nanomaterials will be discussed in light of regulatory requirement for clinical authorization.
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Affiliation(s)
| | - Juan Alberto Ruiz-Pacheco
- West Biomedical Research Center, National Council of Science and Technology, Guadalajara, Jalisco, Mexico
| | - Mohamed Ahmed Elsawy
- Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, Leicester, Leicestershire, UK
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40
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Riaud M, Martinez MC, Montero-Menei CN. Scaffolds and Extracellular Vesicles as a Promising Approach for Cardiac Regeneration after Myocardial Infarction. Pharmaceutics 2020; 12:E1195. [PMID: 33317141 PMCID: PMC7763019 DOI: 10.3390/pharmaceutics12121195] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/03/2020] [Accepted: 12/04/2020] [Indexed: 12/14/2022] Open
Abstract
Clinical studies have demonstrated the regenerative potential of stem cells for cardiac repair over the past decades, but their widespread use is limited by the poor tissue integration and survival obtained. Natural or synthetic hydrogels or microcarriers, used as cell carriers, contribute to resolving, in part, the problems encountered by providing mechanical support for the cells allowing cell retention, survival and tissue integration. Moreover, hydrogels alone also possess mechanical protective properties for the ischemic heart. The combined effect of growth factors with cells and an appropriate scaffold allow a therapeutic effect on myocardial repair. Despite this, the effects obtained with cell therapy remain limited and seem to be equivalent to the effects obtained with extracellular vesicles, key actors in intercellular communication. Extracellular vesicles have cardioprotective effects which, when combined proangiogenic properties with antiapoptotic and anti-inflammatory actions, make it possible to act on all the damages caused by ischemia. The evolution of biomaterial engineering allows us to envisage their association with new major players in cardiac therapy, extracellular vesicles, in order to limit undesirable effects and to envisage a transfer to the clinic. This new therapeutic approach could be associated with the release of growth factors to potentialized the beneficial effect obtained.
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Affiliation(s)
- Melody Riaud
- SOPAM, U1063, INSERM, UNIV Angers, SFR ICAT, F-49800 Angers, France;
- CRCINA, UMR 1232, INSERM, Université de Nantes, Université d’Angers, F-49933 Angers, France
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41
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Selvakumar D, Clayton ZE, Chong JJH. Robust Cardiac Regeneration: Fulfilling the Promise of Cardiac Cell Therapy. Clin Ther 2020; 42:1857-1879. [PMID: 32943195 DOI: 10.1016/j.clinthera.2020.08.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 08/12/2020] [Accepted: 08/14/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE We review the history of cardiac cell therapy, highlighting lessons learned from initial adult stem cell (ASC) clinical trials. We present pluripotent stem cell-derived cardiomyocytes (PSC-CMs) as a leading candidate for robust regeneration of infarcted myocardium but identify several issues that must be addressed before successful clinical translation. METHODS We conducted an unstructured literature review of PubMed-listed articles, selecting the most comprehensive and relevant research articles, review articles, clinical trials, and basic or translation articles in the field of cardiac cell therapy. Articles were identified using the search terms adult stem cells, pluripotent stem cells, cardiac stem cell, and cardiac regeneration or from references of relevant articles, Articles were prioritized and selected based on their impact, originality, or potential clinical applicability. FINDINGS Since its inception, the ASC therapy field has been troubled by conflicting preclinical data, academic controversies, and inconsistent trial designs. These issues have damaged perceptions of cardiac cell therapy among investors, the academic community, health care professionals, and, importantly, patients. In hindsight, the key issue underpinning these problems was the inability of these cell types to differentiate directly into genuine cardiomyocytes, rendering them unable to replace damaged myocardium. Despite this, beneficial effects through indirect paracrine or immunomodulatory effects remain possible and continue to be investigated. However, in preclinical models, PSC-CMs have robustly remuscularized infarcted myocardium with functional, force-generating cardiomyocytes. Hence, PSC-CMs have now emerged as a leading candidate for cardiac regeneration, and unpublished reports of first-in-human delivery of these cells have recently surfaced. However, the cardiac cell therapy field's history should serve as a cautionary tale, and we identify several translational hurdles that still remain. Preclinical solutions to issues such as arrhythmogenicity, immunogenicity, and poor engraftment rates are needed, and next-generation clinical trials must draw on robust knowledge of mechanistic principles of the therapy. IMPLICATIONS The clinical transplantation of functional stem cell-derived heart tissue with seamless integration into native myocardium is a lofty goal. However, considerable advances have been made during the past 2 decades. Currently, PSC-CMs appear to be the best prospect to reach this goal, but several hurdles remain. The history of adult stem cell trials has taught us that shortcuts cannot be taken without dire consequences, and it is essential that progress not be hurried and that a worldwide, cross-disciplinary approach be used to ensure safe and effective clinical translation.
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Affiliation(s)
- Dinesh Selvakumar
- Centre for Heart Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia; Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia
| | - Zoe E Clayton
- Centre for Heart Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
| | - James J H Chong
- Centre for Heart Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia; Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.
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42
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Wang X, Chacon LI, Derakhshandeh R, Rodriguez HJ, Han DD, Kostyushev DS, Henry TD, Traverse JH, Moyé L, Simari RD, Taylor DA, Springer ML. Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials. PLoS One 2020; 15:e0237401. [PMID: 32841277 PMCID: PMC7446972 DOI: 10.1371/journal.pone.0237401] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 07/25/2020] [Indexed: 01/07/2023] Open
Abstract
Implantation of bone marrow-derived cells (BMCs) into mouse hearts post-myocardial infarction (MI) limits cardiac functional decline. However, clinical trials of post-MI BMC therapy have yielded conflicting results. While most laboratory experiments use healthy BMC donor mice, clinical trials use post-MI autologous BMCs. Post-MI mouse BMCs are therapeutically impaired, due to inflammatory changes in BMC composition. Thus, therapeutic efficacy of the BMCs progressively worsens after MI but recovers as donor inflammatory response resolves. The availability of post-MI patient BM mononuclear cells (MNCs) from the TIME and LateTIME clinical trials enabled us to test if human post-MI MNCs undergo a similar period of impaired efficacy. We hypothesized that MNCs from TIME trial patients would be less therapeutic than healthy human donor MNCs when implanted into post-MI mouse hearts, and that therapeutic properties would be restored in MNCs from LateTIME trial patients. Post-MI SCID mice received MNCs from healthy donors, TIME patients, or LateTIME patients. Cardiac function improved considerably in the healthy donor group, but neither the TIME nor LateTIME group showed therapeutic effect. Conclusion: post-MI human MNCs lack therapeutic benefits possessed by healthy MNCs, which may partially explain why BMC clinical trials have been less successful than mouse studies.
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Affiliation(s)
- Xiaoyin Wang
- Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, United States of America
| | | | - Ronak Derakhshandeh
- Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, United States of America
| | - Hilda J. Rodriguez
- Division of Cardiology, University of California, San Francisco, San Francisco, CA, United States of America
- Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, United States of America
| | - Daniel D. Han
- Division of Cardiology, University of California, San Francisco, San Francisco, CA, United States of America
| | - Dmitry S. Kostyushev
- Division of Cardiology, University of California, San Francisco, San Francisco, CA, United States of America
| | - Timothy D. Henry
- The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital, Cincinnati, OH, United States of America
| | - Jay H. Traverse
- Minneapolis Heart Institute Foundation, Minneapolis, MN, United States of America
| | - Lem Moyé
- University of Texas Health School of Public Health, Houston, TX, United States of America
| | - Robert D. Simari
- Kansas University Medical Center, Kansas City, KS, United States of America
| | - Doris A. Taylor
- Texas Heart Institute, Houston, TX, United States of America
| | - Matthew L. Springer
- Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, United States of America
- Division of Cardiology, University of California, San Francisco, San Francisco, CA, United States of America
- Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, United States of America
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43
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Montero P, Flandes-Iparraguirre M, Musquiz S, Pérez Araluce M, Plano D, Sanmartín C, Orive G, Gavira JJ, Prosper F, Mazo MM. Cells, Materials, and Fabrication Processes for Cardiac Tissue Engineering. Front Bioeng Biotechnol 2020; 8:955. [PMID: 32850768 PMCID: PMC7431658 DOI: 10.3389/fbioe.2020.00955] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 07/23/2020] [Indexed: 12/19/2022] Open
Abstract
Cardiovascular disease is the number one killer worldwide, with myocardial infarction (MI) responsible for approximately 1 in 6 deaths. The lack of endogenous regenerative capacity, added to the deleterious remodelling programme set into motion by myocardial necrosis, turns MI into a progressively debilitating disease, which current pharmacological therapy cannot halt. The advent of Regenerative Therapies over 2 decades ago kick-started a whole new scientific field whose aim was to prevent or even reverse the pathological processes of MI. As a highly dynamic organ, the heart displays a tight association between 3D structure and function, with the non-cellular components, mainly the cardiac extracellular matrix (ECM), playing both fundamental active and passive roles. Tissue engineering aims to reproduce this tissue architecture and function in order to fabricate replicas able to mimic or even substitute damaged organs. Recent advances in cell reprogramming and refinement of methods for additive manufacturing have played a critical role in the development of clinically relevant engineered cardiovascular tissues. This review focuses on the generation of human cardiac tissues for therapy, paying special attention to human pluripotent stem cells and their derivatives. We provide a perspective on progress in regenerative medicine from the early stages of cell therapy to the present day, as well as an overview of cellular processes, materials and fabrication strategies currently under investigation. Finally, we summarise current clinical applications and reflect on the most urgent needs and gaps to be filled for efficient translation to the clinical arena.
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Affiliation(s)
- Pilar Montero
- Regenerative Medicine Program, Cima Universidad de Navarra, Foundation for Applied Medical Research, Pamplona, Spain
| | - María Flandes-Iparraguirre
- Regenerative Medicine Program, Cima Universidad de Navarra, Foundation for Applied Medical Research, Pamplona, Spain
| | - Saioa Musquiz
- Regenerative Medicine Program, Cima Universidad de Navarra, Foundation for Applied Medical Research, Pamplona, Spain
- NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country – UPV/EHU, Vitoria-Gasteiz, Spain
| | - María Pérez Araluce
- Regenerative Medicine Program, Cima Universidad de Navarra, Foundation for Applied Medical Research, Pamplona, Spain
- Department of Pharmaceutical Technology and Chemistry, University of Navarra, Pamplona, Spain
| | - Daniel Plano
- Department of Pharmaceutical Technology and Chemistry, University of Navarra, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Carmen Sanmartín
- Department of Pharmaceutical Technology and Chemistry, University of Navarra, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Gorka Orive
- NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country – UPV/EHU, Vitoria-Gasteiz, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- University Institute for Regenerative Medicine and Oral Implantology – UIRMI (UPV/EHU – Fundación Eduardo Anitua), Vitoria-Gasteiz, Spain
- Singapore Eye Research Institute, Singapore, Singapore
| | - Juan José Gavira
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- Cardiology Department, Clínica Universidad de Navarra, Pamplona, Spain
| | - Felipe Prosper
- Regenerative Medicine Program, Cima Universidad de Navarra, Foundation for Applied Medical Research, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- Hematology and Cell Therapy Area, Clínica Universidad de Navarra, Pamplona, Spain
| | - Manuel M. Mazo
- Regenerative Medicine Program, Cima Universidad de Navarra, Foundation for Applied Medical Research, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- Hematology and Cell Therapy Area, Clínica Universidad de Navarra, Pamplona, Spain
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44
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Yao C, Wu W, Tang H, Jia X, Tang J, Ruan X, Li F, Leong DT, Luo D, Yang D. Self-assembly of stem cell membrane-camouflaged nanocomplex for microRNA-mediated repair of myocardial infarction injury. Biomaterials 2020; 257:120256. [PMID: 32736263 DOI: 10.1016/j.biomaterials.2020.120256] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 06/23/2020] [Accepted: 07/21/2020] [Indexed: 12/16/2022]
Abstract
Mesenchymal stem cells-derived exosomes have shown promising therapeutic effect on myocardial infarction (MI). The major hurdles remain for the use of exosomes primarily due to the low yields from cell cultures coupled with complicated purification processes. Herein we report the self-assembly of stem cell membrane-camouflaged exosome-mimicking nanocomplex that recapitulates exosome functions, achieving efficient microRNA (miRNA) delivery and miRNA-mediated myocardial repair. The nanocomplex is constructed via the self-assembly of mesenchymal stem cell membrane on miRNA loaded mesoporous silica nanoparticle surface, which enables high miRNA loading capacity and protects miRNA from degradation in body fluid. The nanocomplex can escape the clearance of immunologic system, and target to ischemic injured cardiomyocytes. miRNA is triggered to release and binds to target mRNA, which inhibits the translation of apoptosis-related proteins, and consequently promotes the proliferation of cardiomyocytes. In the MI mouse model, the administration of exosome-mimicking nanocomplex effectively leads to preservation of viable myocardium and augmentation of cardiac functions.
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Affiliation(s)
- Chi Yao
- Frontier Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China
| | - Weijian Wu
- Frontier Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China
| | - Han Tang
- Frontier Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China
| | - Xuemei Jia
- Frontier Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China
| | - Jianpu Tang
- Frontier Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China
| | - Xinhua Ruan
- Department of Cardiac Surgery, Tianjin Union Medical Centre, Tianjin, 300121, PR China
| | - Feng Li
- Frontier Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China
| | - David Tai Leong
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore
| | - Dan Luo
- Department of Biological & Environmental Engineering, Cornell University, Ithaca, NY, 14853, USA
| | - Dayong Yang
- Frontier Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China.
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45
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He L, Nguyen NB, Ardehali R, Zhou B. Heart Regeneration by Endogenous Stem Cells and Cardiomyocyte Proliferation: Controversy, Fallacy, and Progress. Circulation 2020; 142:275-291. [PMID: 32687441 DOI: 10.1161/circulationaha.119.045566] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Ischemic heart disease is the leading cause of death worldwide. Myocardial infarction results in an irreversible loss of cardiomyocytes with subsequent adverse remodeling and heart failure. Identifying new sources for cardiomyocytes and promoting their formation represents a goal of cardiac biology and regenerative medicine. Within the past decade, many types of putative cardiac stem cells (CSCs) have been reported to regenerate the injured myocardium by differentiating into new cardiomyocytes. Some of these CSCs have been translated from bench to bed with reported therapeutic effectiveness. However, recent basic research studies on stem cell tracing have begun to question their fundamental biology and mechanisms of action, raising serious concerns over the myogenic potential of CSCs. We review the history of different types of CSCs within the past decade and provide an update of recent cell tracing studies that have challenged the origin and existence of CSCs. In addition to the potential role of CSCs in heart regeneration, proliferation of preexisting cardiomyocytes has recently gained more attention. This review will also evaluate the methodologic and technical aspects of past and current studies on CSCs and cardiomyocyte proliferation, with emphasis on technical strengths, advantages, and potential limitations of research approaches. While our understanding of cardiomyocyte generation and regeneration continues to evolve, it is important to address the shortcomings and inaccuracies in this field. This is best achieved by embracing technological advancements and improved methods to label single cardiomyocytes/progenitors and accurately investigate their developmental potential and fate/lineage commitment.
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Affiliation(s)
- Lingjuan He
- State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China (L.H., B.Z.)
| | - Ngoc B Nguyen
- Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine (N.B.N., R.A.), University of California, Los Angeles.,Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research (N.B.N., R.A.), University of California, Los Angeles
| | - Reza Ardehali
- Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine (N.B.N., R.A.), University of California, Los Angeles.,Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research (N.B.N., R.A.), University of California, Los Angeles
| | - Bin Zhou
- State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China (L.H., B.Z.).,School of Life Science and Technology, ShanghaiTech University, Shanghai, China (B.Z.).,School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China (B.Z.).,Key Laboratory of Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China (B.Z.)
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46
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Gastl M, Sürder D, Corti R, Faruque Osmany D, Gotschy A, von Spizcak J, Sokolska J, Metzen D, Alkadhi H, Ruschitzka F, Kozerke S, Manka R. Effect of intracoronary bone marrow-derived mononuclear cell injection early and late after myocardial infarction on CMR-derived myocardial strain. Int J Cardiol 2020; 310:108-115. [DOI: 10.1016/j.ijcard.2020.01.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 12/20/2019] [Accepted: 01/13/2020] [Indexed: 11/24/2022]
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47
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Kung PC, Chien SS, Tsou NT. A Hybrid Model for Predicting Bone Healing around Dental Implants. MATERIALS 2020; 13:ma13122858. [PMID: 32630583 PMCID: PMC7344742 DOI: 10.3390/ma13122858] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 06/22/2020] [Accepted: 06/23/2020] [Indexed: 02/02/2023]
Abstract
BACKGROUND The effect of the short-term bone healing process is typically neglected in numerical models of bone remodeling for dental implants. In this study, a hybrid two-step algorithm was proposed to enable a more accurate prediction for the performance of dental implants. METHODS A mechano-regulation algorithm was firstly used to simulate the tissue differentiation around a dental implant during the short-term bone healing. Then, the result was used as the initial state of the bone remodeling model to simulate the long-term healing of the bones. The algorithm was implemented by a 3D finite element model. RESULTS The current hybrid model reproduced several features which were discovered in the experiments, such as stress shielding effect, high strength bone connective tissue bands, and marginal bone loss. A reasonable location of bone resorptions and the stability of the dental implant is predicted, compared with those predicted by the conventional bone remodeling model. CONCLUSIONS The hybrid model developed here predicted bone healing processes around dental implants more accurately. It can be used to study bone healing before implantation surgery and assist in the customization of dental implants.
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Affiliation(s)
| | | | - Nien-Ti Tsou
- Correspondence: ; Tel.: +886-3-5712121 (ext. 55308)
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48
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Abstract
Stem cell therapy offers a breakthrough opportunity for the improvement of ischemic heart diseases. Numerous clinical trials and meta-analyses appear to confirm its positive but variable effects on heart function. Whereas these trials widely differed in design, cell type, source, and doses reinjected, cell injection route and timing, and type of cardiac disease, crucial key factors that may favour the success of cell therapy emerge from the review of their data. Various types of cell have been delivered. Injection of myoblasts does not improve heart function and is often responsible for severe ventricular arrythmia occurrence. Using bone marrow mononuclear cells is a misconception, as they are not stem cells but mainly a mix of various cells of hematopoietic lineages and stromal cells, only containing very low numbers of cells that have stem cell-like features; this likely explain the neutral results or at best the modest improvement in heart function reported after their injection. The true existence of cardiac stem cells now appears to be highly discredited, at least in adults. Mesenchymal stem cells do not repair the damaged myocardial tissue but attenuate post-infarction remodelling and contribute to revascularization of the hibernated zone surrounding the scar. CD34+ stem cells - likely issued from pluripotent very small embryonic-like (VSEL) stem cells - emerge as the most convincing cell type, inducing structural and functional repair of the ischemic myocardial area, providing they can be delivered in large amounts via intra-myocardial rather than intra-coronary injection, and preferentially after myocardial infarct rather than chronic heart failure.
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Affiliation(s)
- Philippe Hénon
- CellProthera SAS and Institut de Recherche en Hématologie et Transplantation, CellProthera SAS 12 rue du Parc, 68100, Mulhouse, France.
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49
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Peterson KM, Franchi F, Olthoff M, Chen IY, Paulmurugan R, Rodriguez-Porcel M. Pathway-specific reporter genes to study stem cell biology. Stem Cells 2020; 38:808-814. [PMID: 32129537 PMCID: PMC11443457 DOI: 10.1002/stem.3167] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 01/03/2020] [Accepted: 02/04/2020] [Indexed: 01/03/2023]
Abstract
Little is known on the phenotypic characteristics of stem cells (SCs) after they are transplanted to the myocardium, in part due to lack of noninvasive platforms to study SCs directly in the living subject. Reporter gene imaging has played a valuable role in the noninvasive assessment of cell fate in vivo. In this study, we validated a pathway-specific reporter gene that can be used to noninvasively image the phenotype of SCs transplanted to the myocardium. Rat mesenchymal SCs (MSCs) were studied for phenotypic evidence of myogenic characteristics under in vitro conditions. After markers of myogenic characteristics were identified, we constructed a reporter gene sensor, comprising the firefly luciferase (Fluc) reporter gene driven by the troponin T (TnT) promoter (cardio MSCs had threefold expression in polymerase chain reaction compared to control MSCs) using a two-step signal amplification strategy. MSCs transfected with TnT-Fluc were studied and validated under in vitro conditions, showing a strong signal after MSCs acquired myogenic characteristics. Lastly, we observed that cardio MSCs had higher expression of the reporter sensor compared to control cells (0.005 ± 0.0005 vs 0.0025 ± 0.0008 Tnt-Fluc/ubiquitin-Fluc, P < .05), and that this novel sensor can detect the change in the phenotype of MSCs directly in the living subject. Pathway-specific reporter gene imaging allows assessment of changes in the phenotype of MSCs after delivery to the ischemic myocardium, providing important information on the phenotype of these cells. Imaging sensors like the one described here are critical to better understanding of the changes that SCs undergo after transplantation.
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Affiliation(s)
- Karen M Peterson
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Federico Franchi
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Michaela Olthoff
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Ian Y Chen
- Cardiology Section, Medical Services, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
- Cardiovascular Institute, Stanford University, Stanford, California, USA
| | - Ramasamy Paulmurugan
- Cardiovascular Institute, Stanford University, Stanford, California, USA
- Department of Radiology and Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, California, USA
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50
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Audam TN, Nong Y, Tomlin A, Jurkovic A, Li H, Zhu X, Long BW, Zheng YW, Weirick T, Brittian KR, Riggs DW, Gumpert A, Uchida S, Guo Y, Wysoczynski M, Jones SP. Cardiac mesenchymal cells from failing and nonfailing hearts limit ventricular dilation when administered late after infarction. Am J Physiol Heart Circ Physiol 2020; 319:H109-H122. [PMID: 32442025 DOI: 10.1152/ajpheart.00114.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Although cell therapy-mediated cardiac repair offers promise for treatment/management of heart failure, lack of fundamental understanding of how cell therapy works limits its translational potential. In particular, whether reparative cells from failing hearts differ from cells derived from nonfailing hearts remains unexplored. Here, we assessed differences between cardiac mesenchymal cells (CMC) derived from failing (HF) versus nonfailing (Sham) hearts and whether the source of donor cells (i.e., from HF vs. Sham) limits reparative capacity, particularly when administered late after infarction. To determine the impact of the donor source of CMCs, we characterized the transcriptional profile of CMCs isolated from sham (Sham-CMC) and failing (HF-CMC) hearts. RNA-seq analysis revealed unique transcriptional signatures in Sham-CMC and HF-CMC, suggesting that the donor source impacts CMC. To determine whether the donor source affects reparative potential, C57BL6/J female mice were subjected to 60 min of regional myocardial ischemia and then reperfused for 35 days. In a randomized, controlled, and blinded fashion, vehicle, HF-CMC, or Sham-CMC were injected into the lumen of the left ventricle at 35 days post-MI. An additional 5 weeks later, cardiac function was assessed by echocardiography, which indicated that delayed administration of Sham-CMC and HF-CMC attenuated ventricular dilation. We also determined whether Sham-CMC and HF-CMC treatments affected ventricular histopathology. Our data indicate that the donor source (nonfailing vs. failing hearts) affects certain aspects of CMC, and these insights may have implications for future studies. Our data indicate that delayed administration of CMC limits ventricular dilation and that the source of CMC may influence their reparative actions.NEW & NOTEWORTHY Most preclinical studies have used only cells from healthy, nonfailing hearts. Whether donor condition (i.e., heart failure) impacts cells used for cell therapy is not known. We directly tested whether donor condition impacted the reparative effects of cardiac mesenchymal cells in a chronic model of myocardial infarction. Although cells from failing hearts differed in multiple aspects, they retained the potential to limit ventricular remodeling.
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Affiliation(s)
- Timothy N Audam
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Yibing Nong
- Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Alex Tomlin
- Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Andrea Jurkovic
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Hong Li
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Xiaoping Zhu
- Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Bethany W Long
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Yi Wei Zheng
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Tyler Weirick
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky.,Cardiovascular Innovation Institute, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Kenneth R Brittian
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Daniel W Riggs
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Anna Gumpert
- Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Shizuka Uchida
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky.,Cardiovascular Innovation Institute, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Yiru Guo
- Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Marcin Wysoczynski
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Steven P Jones
- Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky
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