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1
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Wang M, Xin Y, Cao H, Li W, Hua Y, Webster TJ, Zhang C, Tang W, Liu Z. Recent advances in mesenchymal stem cell membrane-coated nanoparticles for enhanced drug delivery. Biomater Sci 2020; 9:1088-1103. [PMID: 33332490 DOI: 10.1039/d0bm01164a] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Studies of nanomedicine have achieved dramatic progress in recent decades. However, the main challenges that traditional nanomedicine has to overcome include low accumulation at target sites and rapid clearance from the blood circulation. An interesting approach using cell membrane coating technology has emerged as a possible way to overcome these limitations, owing to the enhanced targeted delivery and reduced immunogenicity of cell membrane moieties. Mesenchymal stem cell (MSC) therapy has been investigated for treating various diseases, ranging from inflammatory diseases to tissue damage. Recent studies with engineered modified MSCs or MSC membranes have focused on enhancing cell therapeutic efficacy. Therefore, bioengineering strategies that couple synthetic nanoparticles with MSC membranes have recently received much attention due to their homing ability and tumor tropism. Given the various membrane receptors on their surfaces, MSC membrane-coated nanoparticles are an effective method with selective targeting properties, allowing entry into specific cells. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for biomedical applications, particularly in the two main antitumor and anti-inflammatory fields. The combination of a bioengineered cell membrane and synthesized nanoparticles presents a wide range of possibilities for the further development of targeted drug delivery, showing the potential to enhance the therapeutic efficacy for treating various diseases.
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Affiliation(s)
- Mian Wang
- Department of Cardiology, Research Center for Translational Medicine, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
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2
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Brambati M, Borrelli E, Sacconi R, Bandello F, Querques G. Choroideremia: Update On Clinical Features And Emerging Treatments. Clin Ophthalmol 2019; 13:2225-2231. [PMID: 31819346 PMCID: PMC6874149 DOI: 10.2147/opth.s195564] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 11/05/2019] [Indexed: 12/21/2022] Open
Abstract
Choroideremia (CHM) is an X-linked chorioretinal dystrophy characterized by progressive degeneration of the choroid, retinal pigment epithelium and retina. This disease is caused by mutations in the X-linked CHM gene encoding a Ras-related GTPase Rab escort protein (REP)-1, which is extremely important for the retinal function. Clinically, male-affected patients have a progressive reduction in visual acuity. This disease is formally considered incurable, although new promising treatments have been recently introduced. In this article, a review of the salient pathogenetic features of choroideremia, essential for the proper interpretation of therapeutic approaches, is followed by a discussion of the fundamental clinical features of this hereditary disease. Finally, relevant new therapeutic approaches in this disease will be discussed, including gene therapy, stem cells, small molecules, and retinal prosthesis.
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Affiliation(s)
- Maria Brambati
- Ophthalmology Department, San Raffaele University Hospital, Milan, Italy
| | - Enrico Borrelli
- Ophthalmology Department, San Raffaele University Hospital, Milan, Italy
| | - Riccardo Sacconi
- Ophthalmology Department, San Raffaele University Hospital, Milan, Italy
| | - Francesco Bandello
- Ophthalmology Department, San Raffaele University Hospital, Milan, Italy
| | - Giuseppe Querques
- Ophthalmology Department, San Raffaele University Hospital, Milan, Italy
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3
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Carvalho KATD, Abdelwahid E, Ferreira RJ, Irioda AC, Guarita-Souza LC. Preclinical stem cell therapy in Chagas Disease: Perspectives for future research. World J Transplant 2013; 3:119-126. [PMID: 24392316 PMCID: PMC3879521 DOI: 10.5500/wjt.v3.i4.119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 10/18/2013] [Indexed: 02/05/2023] Open
Abstract
Chagas cardiomyopathy still remains a challenging problem that is responsible for high morbidity and mortality in Central and Latin America. Chagas disease disrupts blood microcirculation via various autoimmune mechanisms, causing loss of cardiomyocytes and severe impairment of heart function. Different cell types and delivery approaches in Chagas Disease have been studied in both preclinical models and clinical trials. The main objective of this article is to clarify the reasons why the benefits that have been seen with cell therapy in preclinical models fail to translate to the clinical setting. This can be explained by crucial differences between the cellular types and pathophysiological mechanisms of the disease, as well as the differences between human patients and animal models. We discuss examples that demonstrate how the results from preclinical trials might have overestimated the efficacy of myocardial regeneration therapies. Future research should focus, not only on studying the best cell type to use but, very importantly, understanding the levels of safety and cellular interaction that can elicit efficient therapeutic effects in human tissue. Addressing the challenges associated with future research may ensure the success of stem cell therapy in improving preclinical models and the treatment of Chagas disease.
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Díez Villanueva P, Sanz-Ruiz R, Núñez García A, Fernández Santos ME, Sánchez PL, Fernández-Avilés F. Functional multipotency of stem cells: what do we need from them in the heart? Stem Cells Int 2012; 2012:817364. [PMID: 22966237 PMCID: PMC3433152 DOI: 10.1155/2012/817364] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Revised: 07/22/2012] [Accepted: 07/22/2012] [Indexed: 12/14/2022] Open
Abstract
After more than ten years of human research in the field of cardiac regenerative medicine, application of stem cells in different phases of ischemic heart disease has come to age. Randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease, and several efficacy phase III trials with clinical endpoints are on their way. Nevertheless, a complete knowledge on the mechanisms of action of stem cells still remains elusive. Of the three main mechanisms by which stem cells could exert their benefit, paracrine signaling from the administered cells and stimulation of endogenous repair are nowadays the most plausible ones. However, in this review we will define and discuss the concept of stem cell potency and differentiation, will examine the evidence available, and will depict future directions of research.
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Affiliation(s)
- Pablo Díez Villanueva
- Cardiology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Ricardo Sanz-Ruiz
- Cardiology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Alberto Núñez García
- Cardiology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | - Pedro L. Sánchez
- Cardiology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Venugopal JR, Prabhakaran MP, Mukherjee S, Ravichandran R, Dan K, Ramakrishna S. Biomaterial strategies for alleviation of myocardial infarction. J R Soc Interface 2011; 9:1-19. [PMID: 21900319 PMCID: PMC3223634 DOI: 10.1098/rsif.2011.0301] [Citation(s) in RCA: 137] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
World Health Organization estimated that heart failure initiated by coronary artery disease and myocardial infarction (MI) leads to 29 per cent of deaths worldwide. Heart failure is one of the leading causes of death in industrialized countries and is expected to become a global epidemic within the twenty-first century. MI, the main cause of heart failure, leads to a loss of cardiac tissue impairment of left ventricular function. The damaged left ventricle undergoes progressive ‘remodelling’ and chamber dilation, with myocyte slippage and fibroblast proliferation. Repair of diseased myocardium with in vitro-engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for heart failure patients. These events reflect an apparent lack of effective intrinsic mechanism for myocardial repair and regeneration. Motivated by the desire to develop minimally invasive procedures, the last 10 years observed growing efforts to develop injectable biomaterials with and without cells to treat cardiac failure. Biomaterials evaluated include alginate, fibrin, collagen, chitosan, self-assembling peptides, biopolymers and a range of synthetic hydrogels. The ultimate goal in therapeutic cardiac tissue engineering is to generate biocompatible, non-immunogenic heart muscle with morphological and functional properties similar to natural myocardium to repair MI. This review summarizes the properties of biomaterial substrates having sufficient mechanical stability, which stimulates the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering.
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Affiliation(s)
- Jayarama Reddy Venugopal
- Healthcare and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore.
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6
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Abstract
Hematopoietic, stromal and organ-specific stem cells are under evaluation for therapeutic efficacy in cell-based therapies of cardiac, neurological and other disorders. It is critically important to track the location of directly transplanted or infused cells that can serve as gene carrier/delivery vehicles for the treatment of disease processes and be able to noninvasively monitor the temporal and spatial homing of these cells to target tissues. Moreover, it is also necessary to determine their engraftment efficiency and functional capability following transplantation. There are various in vivo imaging modalities used to track the movement and incorporation of administered cells. Tagging stem cells with different contrast agents can make these cells probes for different imaging modalities. Recent reports have shown that stem cells labeled with iron oxides can be used as cellular MRI probes demonstrating the cell trafficking to target tissues. In this review, we will discuss the status and future prospect of stem cell tracking by cellular MRI for cell-based therapy.
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Affiliation(s)
- Ali S Arbab
- Henry Ford Hospital, Cellular & Molecular Imaging Laboratory,Department of Radiology, 1 Ford Place, 2F Detroit, MI 48202, USA.
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McGuckin CP, Forraz N. Potential for access to embryonic-like cells from human umbilical cord blood. Cell Prolif 2008; 41 Suppl 1:31-40. [PMID: 18181943 DOI: 10.1111/j.1365-2184.2008.00490.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
All too often media attention clouds the reality that there are many types of stem cell. The embryos, bone marrow and umbilical cord blood (UCB) are the three most used sources. However, despite what it would appear, embryonic stem cells have not been the first to yield life-saving cures at present. Faster routes to clinical intervention have been using adult stem cells that can be sourced from bone marrow and from cord blood, and that are readily accessible and are more ethically acceptable to the general public. Both these non-embryonic sources have been able to provide sufficient numbers of cells to allow development of clinical translational protocols. Bone marrow-derived cells have been used successfully in myocardial infarct therapy where relining by endothelial tissue has allowed limited reperfusion to damaged cardiac tissue. UCB have also demonstrated significant success for around 20 years in haematotransplantation. With a global human population in excess of 6 billion, births thus UCB, remain the largest untouched source of stem cells available every year. UCB also provide a distinct advantage over other adult stem cells due to the length of the telomere and also due protected immunological status of the developing neonatal environment. The total mutation load in the UCB populations is clearly likely to be significant less than in adult tissues.
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Affiliation(s)
- C P McGuckin
- Newcastle Centre for Cord Blood, Stem Cell Institute, Medical School, Newcastle upon Tyne, UK.
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8
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Arbab AS, Rad AM, Iskander ASM, Jafari-Khouzani K, Brown SL, Churchman JL, Ding G, Jiang Q, Frank JA, Soltanian-Zadeh H, Peck DJ. Magnetically-labeled sensitized splenocytes to identify glioma by MRI: a preliminary study. Magn Reson Med 2007; 58:519-26. [PMID: 17763342 DOI: 10.1002/mrm.21343] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
This study investigated the feasibility of imaging the migration and incorporation of magnetically-labeled sensitized splenocytes in an experimental 9L glioma brain tumor model. Splenocytes collected from tumor-bearing (sensitized splenocytes) or control (nonsensitized splenocytes) host rats were analyzed to determine the population of different cells, labeled with ferumoxides-protamine sulfate (FePro) and injected intravenously to recipient rats (N=4, for each group) bearing intracranial 9L tumors. Day 3 postinjection of splenocytes multiecho T2*-weighted and three-dimensional (3D) gradient echo MRI were obtained using a 7 Tesla MR system. R2* (1/T2*) maps were created from the T2*-weighted images. Signal intensities (SIs) and R2* values in the tumors and contralateral brain were determined by hand drawn regions of interest (ROIs). Brain sections were stained for the evidence of administered cells. Both 3D and T2*-weighted MRI showed low signal intensity areas in and around the tumors in rats that received labeled sensitized splenocytes. Prussian blue (PB), CD45- and CD8-positive cells were present in areas at the corresponding sites of low signal intensities seen on MRI. Rats that received labeled nonsensitized splenocytes did not show low signal intensity areas or PB positive cells in or around the implanted tumors. In conclusion, the immunogenic reaction can be exploited to delineate recurrent glioma using MRI following systemically delivered magnetically labeled sensitized splenocytes or T-cells.
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Affiliation(s)
- Ali S Arbab
- Department of Radiology, Henry Ford Hospital, Detroit, Michigan 48202, USA, and National Institutes of Health, University of Tehran, Iran.
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Denner L, Bodenburg Y, Zhao JG, Howe M, Cappo J, Tilton RG, Copland JA, Forraz N, McGuckin C, Urban R. Directed engineering of umbilical cord blood stem cells to produce C-peptide and insulin. Cell Prolif 2007; 40:367-80. [PMID: 17531081 PMCID: PMC6496474 DOI: 10.1111/j.1365-2184.2007.00439.x] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVES In this study, we investigated the potential of umbilical cord blood stem cell lineages to produce C-peptide and insulin. MATERIALS AND METHODS Lineage negative, CD133+ and CD34+ cells were analyzed by flow cytometry to assess expression of cell division antigens. These lineages were expanded in culture and subjected to an established protocol to differentiate mouse embryonic stem cells (ESCs) toward the pancreatic phenotype. Phase contrast and fluorescence immunocytochemistry were used to characterize differentiation markers with particular emphasis on insulin and C-peptide. RESULTS All 3 lineages expressed SSEA-4, a marker previously reported to be restricted to the ESC compartment. Phase contrast microscopy showed all three lineages recapitulated the treatment-dependent morphological changes of ESCs as well as the temporally restricted expression of nestin and vimentin during differentiation. After engineering, each isolate contained both C-peptide and insulin, a result also obtained following a much shorter protocol for ESCs. CONCLUSIONS Since C-peptide can only be derived from de novo synthesis and processing of pre-proinsulin mRNA and protein, we conclude that these results are the first demonstration that human umbilical cord blood-derived stem cells can be engineered to engage in de novo synthesis of insulin.
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Affiliation(s)
- L Denner
- Stark Diabetes Center and McCoy Diabetes Mass Spectrometry Research Laboratory, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-1060, USA.
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Airan B, Talwar S, Choudhary SK, Bisoi AK, Chowdhury UK, Hote MP, Mohanty S, Seth S, Patel C, Venugopal P. Application of stem cell technology for coronary artery disease at the All India Institute of Medical Sciences, New Delhi, India. Heart Surg Forum 2007; 10:E231-4. [PMID: 17599898 DOI: 10.1532/hsf98.20070701] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Stem cell technology is rapidly gaining popularity as a way to improve the prognosis of patients with coronary artery disease and heart failure. In this review, we systematically analyze the basis, methods, and results of stem cell technology for coronary artery disease at the All India Institute of Medical Sciences, New Delhi, India.
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Affiliation(s)
- Balram Airan
- Cardiothoracic Centre, All India Institute of Medical Sciences, New Delhi, India.
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11
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Abstract
Cardiac hypertrophy and heart failure are major causes of morbidity and mortality in Western societies. Many factors have been implicated in cardiac remodeling, including alterations in gene expression in myocytes, cardiomyocytes apoptosis, cytokines and growth factors that influence cardiac dynamics, and deficits in energy metabolism as well as alterations in cardiac extracellular matrix composition. Many therapeutic means have been shown to prevent or reverse cardiac hypertrophy. New concepts for characterizing the pathophysiology of cardiac hypertrophy have been drawn from various aspects, including medical therapy and gene therapy, or use of stem cells for tissue regeneration. In this review, we focus on various types of cardiac hypertrophy, defining the causes of hypertrophy, describing available animal models of hypertrophy, discussing the mechanisms for development of hypertrophy and its transition to heart failure, and presenting the potential use of novel promising therapeutic strategies derived from new advances in basic scientific research.
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Affiliation(s)
- Sudhiranjan Gupta
- Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio 44195, USA
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12
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Abstract
Viable treatment options are becoming available for the 'no-option' patient with chronic ischaemic heart disease. Instead of revascularising the highly diseased epicardial coronary arteries, scientists and clinicians have been looking at augmenting mother nature's way of providing biological bypass in an attempt to provide symptomatic relief in these patients. The novel use of gene and cell therapies for myocardial neovascularisation has exploded into a flurry of early clinical trials. This translational research has been motivated by an improved understanding of the biological mechanisms involved in tissue repair after ischaemic injury. While safety concerns will be top in priority in these trials, different types or combination of therapies, dose and route of delivery are being tested before further optimisation and establishment. With cautious optimism, a new era in the treatment of ischaemic heart disease is being entered. This article reviews the present state in gene and cell therapies for ischaemic heart disease, the modalities of their delivery, novel imaging techniques and future perspectives.
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Affiliation(s)
- Kian-Keong Poh
- Caritas St Elizabeth's Medical Center and Tufts University School of Medicine, Boston, MA, USA.
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13
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Abstract
Cardiomyopathy is a common clinical disorder affecting the heart muscle. This disease process frequently leads to congestive heart failure and will often progress to end-stage heart failure. Present standard of care treatment options for cardiomyopathy include medical management, lifestyle changes, and surgical procedures including left ventricular assist devices as a destiny therapy or bridging to heart transplantation. Even despite advances in drug therapy, mechanical assist devices, and organ transplantation, more than half of the persons with cardiomyopathy will die within 5 years of diagnosis. Small uncontrolled clinical trials have demonstrated cardiac stem cells as a treatment option for cardiomyopathy. The theory for the individual or combined mechanism of action for stem cells includes (1) transdifferentiation to blood vessels or myocardium, (2) fusion with the native dysfunctional myocytes to augment function, and (3) homing that may be a systemic or panacrine response for recruiting other cells, and growth factors to help improve oxygen delivery and myocardial function. The field of cardiac cell therapy is rapidly progressing to gather more data with intermediate-size, double-blinded trials that will demonstrate the safety and efficacy of cell therapy.
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14
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Körbling M, Reuben JM, Gao H, Lee BN, Harris DM, Cogdell D, Giralt SA, Khouri IF, Saliba RM, Champlin RE, Zhang W, Estrov Z. Recombinant human granulocyte-colony-stimulating factor-mobilized and apheresis-collected endothelial progenitor cells: a novel blood cell component for therapeutic vasculogenesis. Transfusion 2006; 46:1795-802. [PMID: 17002637 DOI: 10.1111/j.1537-2995.2006.00985.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Endothelial progenitor cells (EPCs) have been identified among hematopoietic tissue-derived progenitor cells that are mobilized into the peripheral blood (PB) as a result of tissue injury. It therefore seems likely that circulating EPCs have therapeutic potential by aiding in the neovascularization of ischemic tissue. This study provides clinical data on the availability of circulating EPCs at steady state and after recombinant human granulocyte-colony-stimulating factor (rHuG-CSF) mobilization and their collection by leukapheresis. STUDY DESIGN AND METHODS Eight healthy donors underwent rHuG-CSF treatment over 4 days, followed by leukapheresis. Blood samples taken before rHuG-CSF treatment and before apheresis as well as apheresis-collected samples were analyzed by flow cytometry and by real time reverse transcription-polymerase chain reaction for cells expressing EPC-specific surface markers and tissue markers, respectively, and for EPC colony-forming cells. RESULTS The median PB concentration of CD34+133+ vascular endothelial growth factor receptor-2 (VEGFR-2)-+ EPCs increased 8-fold from steady state to mobilized, and the concentration of CD34+133-VEGFR-2+ EPCs increased by 10-fold. This mobilization pattern was similar to that of hematopoietic CD34+, CD133+, and CD34+117+ progenitor cells. The increase in the median circulating colony-forming unit EPC concentration was 10-fold over baseline. The median absolute number of CD34+133+VEGFR-2+ cells collected by large-volume leukapheresis was 0.8 x 10(6) per kg of body weight. In addition, a small subset of immature CD133+34- cells coexpressing VEGFR-2 was identified in mobilized PB and in the apheresis collection. EPC-specific cells contained in the apheresis product were also identified as expressing mRNA for the CD31 antigen, Tie-2, and VEGFR-2. CONCLUSION Circulating EPCs represent a novel blood cell component that can be collected by apheresis in large quantities and can be used clinically, either unmanipulated or EPC-selected, for therapeutic vasculogenesis.
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Affiliation(s)
- Martin Körbling
- Department of Blood and Marrow Transplantation, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
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15
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Abstract
Stem cell research and its clinical application have become political, social, and medical lightning rods, polarizing opinion among members of the lay community and among medical/scientific professionals. A potpourri of opinion, near-anecdotal observation, and scientifically sound data has sown confusion in ways rarely seen in the medical arts and sciences. A major issue is regulation, with different aspects of stem cell research falling within the purview of different government agencies and local offices. An overarching clearinghouse to review the field and recommend policy is lacking. In the following pages, I touch on the societal framework for regulation, the known and potential risks and benefits of cardiovascular stem cell therapies, whether stem cells should be regulated as drugs or in analogy to drugs, and if there is to be regulation, then by whom. In so doing, I refer to the stem cell literature only as it relates to the discussion of regulation because this is not a review of stem cell research; it is an opinion regarding regulation.
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Affiliation(s)
- Michael R Rosen
- College of Physicians and Surgeons of Columbia University, Department of Pharmacology, 630 W 168 St, PH 7West-321, New York, NY 10032, USA.
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16
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Hamman BL, White CH, Cheung EHK, Hebeler RF, Kourlis H, Meyers TP, Wood RE, Lansing AM. Transmyocardial laser revascularization causes sustained VEGF secretion. Semin Thorac Cardiovasc Surg 2006; 18:43-5. [PMID: 16766253 DOI: 10.1053/j.semtcvs.2006.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2006] [Indexed: 11/11/2022]
Abstract
Transmyocardial laser revascularization (TMR) using a carbon dioxide (CO(2)) laser has been shown to relieve angina, increase vascular density, and improve myocardial contraction. A study of 28 patients receiving TMR was conducted to monitor vascular endothelial growth factor (VEGF) levels with the goal of clarifying the relationship between TMR, the amelioration of angina, and vascular density. Serum VEGF levels were measured during four periods (preoperative, postoperative, convalescence, and late) in these 28 patients who received sole therapy TMR for un-revascularizable ischemic angina and the levels were compared with the control group consisting of 10 nonischemic thoracotomy patients. Twelve of the 28 patients had previous coronary artery bypass graft(s); 10 had unstable angina, and 1 had an ejection fraction less than 30%. Overall, angina class was reduced from 3.8 +/- 0.9 to 1.0 +/- 0.9 (P < 0.01) at the 1-year follow-up. There were no perioperative mortalities; however, there was one late mortality. The results show that VEGF levels were higher in the convalescence and late periods. Specifically in the late period, VEGF levels in TMR therapy patients surpassed those of the control group and normalized VEGF levels were three times higher in the late period than preoperatively. The sustained VEGF secretion observed in this study may help to explain why CO(2) TMR therapy causes locally increased vascular density and angina relief.
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Affiliation(s)
- Baron L Hamman
- Division of Cardiovascular Surgery, Baylor University Medical Center, Dallas, TX 75226, USA.
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17
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Kofidis T, Lebl DR, Martinez EC, Hoyt G, Tanaka M, Robbins RC. Novel injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury. Circulation 2006; 112:I173-7. [PMID: 16159811 DOI: 10.1161/circulationaha.104.526178] [Citation(s) in RCA: 136] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Implantation of bioartificial patches distorts myocardial geometry, and functional improvement of the recipient heart is usually attributed to reactive angiogenesis around the graft. With the liquid bioartificial tissue compound used in this study, we achieved targeted large-scale support of the infarcted left ventricular wall and improvement of heart function. METHODS AND RESULTS A liquid compound consisting of growth factor-free Matrigel and 10(6) green fluorescent protein (GFP)-positive mouse (129sv) embryonic stem cells (ESCs) was generated and injected into the area of ischemia after ligation of the left anterior descending artery in BALB/c mice (group I). Left anterior descending artery-ligated mice (group II) and mice with Matrigel (group III) or ESC treatment alone (group IV) were used as the control groups (n=5 in all groups). The hearts were harvested for histology 2 weeks later after echocardiographic assessment with a 15-MHz probe. The liquid injectable tissue solidified at body temperature and retained the geometry of the infarcted lateral wall. Immunofluorescence stains revealed voluminous GFP grafts. The quality of restoration (graft/infarct area ratio) was 45.5+/-10.8% in group I and 29.1+/-6.7% in group IV (P=0.034). ESCs expressed connexin 43 at intercellular contact sites. The mice treated with the compound had a superior heart function compared with the controls (P<0.0001 by ANOVA/Bonferroni test; group I: 27.1+/-5.4, group II:11.9+/-2.4, group III:16.2+/-2.8, group IV: 19.1+/-2.7). CONCLUSIONS Injectable bioartificial tissue restores the heart's geometry and function in a targeted and nondistorting fashion. This new method paves the way for novel interventional approaches to myocardial repair, using both stem cells and matrices.
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MESH Headings
- Animals
- Bioartificial Organs
- Chemical Phenomena
- Chemistry, Physical
- Collagen
- Connexin 43/biosynthesis
- Drug Combinations
- Genes, Reporter
- Genes, Synthetic
- Green Fluorescent Proteins/analysis
- Green Fluorescent Proteins/genetics
- Heart Ventricles
- Injections, Intramuscular
- Laminin
- Mice
- Mice, Inbred BALB C
- Myocardial Contraction
- Myocardial Infarction/complications
- Myocardial Infarction/physiopathology
- Myocardial Infarction/surgery
- Peptide Elongation Factor 1/genetics
- Promoter Regions, Genetic
- Proteoglycans
- Stem Cell Transplantation/methods
- Stem Cells/metabolism
- Tissue Engineering
- Ventricular Dysfunction, Left/etiology
- Ventricular Dysfunction, Left/physiopathology
- Ventricular Dysfunction, Left/surgery
- Ventricular Function, Left
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Affiliation(s)
- Theo Kofidis
- Cardiovascular Surgery, Stanford University Medical School, Stanford, California, USA.
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18
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Weiss ML, Troyer DL. Stem cells in the umbilical cord. STEM CELL REVIEWS 2006; 2:155-62. [PMID: 17237554 PMCID: PMC3753204 DOI: 10.1007/s12015-006-0022-y] [Citation(s) in RCA: 240] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/1999] [Revised: 11/30/1999] [Accepted: 11/30/1999] [Indexed: 12/26/2022]
Abstract
Stem cells are the next frontier in medicine. Stem cells are thought to have great therapeutic and biotechnological potential. This will not only to replace damaged or dysfunctional cells, but also rescue them and/or deliver therapeutic proteins after they have been engineered to do so. Currently, ethical and scientific issues surround both embryonic and fetal stem cells and hinder their widespread implementation. In contrast, stem cells recovered postnatally from the umbilical cord, including the umbilical cord blood cells, amnion/placenta, umbilical cord vein, or umbilical cord matrix cells, are a readily available and inexpensive source of cells that are capable of forming many different cell types (i.e., they are "multipotent"). This review will focus on the umbilical cord-derived stem cells and compare those cells with adult bone marrow-derived mesenchymal stem cells.
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Affiliation(s)
- Mark L Weiss
- The Midwest Institute for Comparative Stem Cell Biology and the Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506-5602, USA.
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Bax JJ, Poldermans D, Elhendy A, Boersma E, van der Wall EE. Assessment of myocardial viability by nuclear imaging techniques. Curr Cardiol Rep 2005; 7:124-9. [PMID: 15717959 DOI: 10.1007/s11886-005-0024-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The assessment of myocardial viability has become important in the diagnostic and prognostic work up of patients with ischemic cardiomyopathy. Patients with viable myocardium may benefit from revascularization in terms of improvement of function, symptoms, and prognosis. In contrast, patients without viable myocardium do not benefit and should be treated conservatively. Various nuclear imaging techniques are available.
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Affiliation(s)
- Jeroen J Bax
- Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
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