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Molecular Biomarkers in Perthes Disease: A Review. Diagnostics (Basel) 2023; 13:diagnostics13030471. [PMID: 36766577 PMCID: PMC9914190 DOI: 10.3390/diagnostics13030471] [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] [Received: 12/18/2022] [Revised: 01/06/2023] [Accepted: 01/16/2023] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. METHODS The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. CONCLUSIONS Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.
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Khullar L, Harjai K, Chhibber S. Therapeutic and pro-healing potential of advanced wound dressings loaded with bioactive agents. Future Microbiol 2023; 18:43-63. [PMID: 36537228 DOI: 10.2217/fmb-2022-0162] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Chronic skin wound infections are inextricably linked with high mortality rates. With the rise in the aging population and the threat of diabetes, obesity and lifestyle-based diseases, the risk incurred from invasive wound pathogens has been ever escalating. Thus, more efficacious wound care management is necessary to cope with such morbid illnesses. A plethora of bioactive agents, such as antibiotics, phytochemicals, essential oils, phages among others, has been exploited to develop wound dressings, raising tremendous interest in their prospective use as wound care products. The present review critically focuses on the therapeutic implications of advanced wound dressings that have assisted in the expansion of regenerative medicine and also discusses the practical concerns that have limited their bench-to-market entry.
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Affiliation(s)
- Lavanya Khullar
- Department of Microbiology, Panjab University, Chandigarh, India
| | - Kusum Harjai
- Department of Microbiology, Panjab University, Chandigarh, India
| | - Sanjay Chhibber
- Department of Microbiology, Panjab University, Chandigarh, India
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Ahn S, Koh BI, Lee J, Hong S, Kim I, Kim P. In vivo observation of multi-phase spatiotemporal cellular dynamics of transplanted HSPCs during early engraftment. FASEB Bioadv 2022; 4:547-559. [PMID: 35949509 PMCID: PMC9353502 DOI: 10.1096/fba.2021-00164] [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: 12/22/2021] [Revised: 04/18/2022] [Accepted: 04/26/2022] [Indexed: 11/11/2022] Open
Abstract
Hematopoietic stem cell transplantation (HSCT) is commonly used to treat patients with various blood disorders, genetic and immunological diseases, and solid tumors. Several systemic complications following HSCT are critical limiting factors for achieving a successful outcome. These systemic complications are mainly due to the lack of initial engraftment after transplantation. However, the detailed underlying cellular dynamics of early engraftment have not been fully characterized yet. We performed in vivo longitudinal visualization of early engraftment characteristics of transplanted hematopoietic stem and progenitor cells (HSPCs) in the mouse calvarial bone marrow (BM). To achieve this, we utilized an in vivo laser-scanning confocal microscopy imaging system with a cranial BM imaging window and stereotaxic device. We observed two distinct cellular behaviors of HSPCs in vivo, cluster formation and cluster dissociation, early after transplantation. Furthermore, we successfully identified three cellular phases of engraftment with distinct cellular distances which are coordinated with cell proliferation and cell migration dynamics during initial engraftment.
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Affiliation(s)
- Soyeon Ahn
- Graduate School of Nanoscience and TechnologyKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
- KI for Health Science and Technology (KIHST)Korea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
- IVIM TechnologyDaejeonRepublic of Korea
| | - Bong Ihn Koh
- KI for the BioCenturyKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
- Max Planck Institute for Molecular BiomedicineDepartment of Tissue MorphogenesisUniversity of MünsterFaculty of MedicineMünsterGermany
| | - Jingu Lee
- Graduate School of Nanoscience and TechnologyKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
- KI for Health Science and Technology (KIHST)Korea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
| | - Sujung Hong
- Graduate School of Nanoscience and TechnologyKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
- KI for Health Science and Technology (KIHST)Korea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
| | - Injune Kim
- Graduate School of Medical Science and EngineeringKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
| | - Pilhan Kim
- Graduate School of Nanoscience and TechnologyKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
- KI for Health Science and Technology (KIHST)Korea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
- IVIM TechnologyDaejeonRepublic of Korea
- Graduate School of Medical Science and EngineeringKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
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Synthesis, photophysical characterization, relaxometric studies and molecular docking studies of gadolinium-free contrast agents for dual modal imaging. RESULTS IN CHEMISTRY 2022. [DOI: 10.1016/j.rechem.2022.100307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
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Ebhodaghe SO. Natural Polymeric Scaffolds for Tissue Engineering Applications. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2021; 32:2144-2194. [PMID: 34328068 DOI: 10.1080/09205063.2021.1958185] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Natural polymeric scaffolds can be used for tissue engineering applications such as cell delivery and cell-free supporting of native tissues. This is because of their desirable properties such as; high biocompatibility, tunable mechanical strength and conductivity, large surface area, porous- and extracellular matrix (ECM)-mimicked structures. Specifically, their less toxicity and biocompatibility makes them suitable for several tissue engineering applications. For these reasons, several biopolymeric scaffolds are currently being explored for numerous tissue engineering applications. To date, research on the nature, chemistry, and properties of nanocomposite biopolymers are been reported, while the need for a comprehensive research note on more tissue engineering application of these biopolymers remains. As a result, this present study comprehensively reviews the development of common natural biopolymers as scaffolds for tissue engineering applications such as cartilage tissue engineering, cornea repairs, osteochondral defect repairs, and nerve regeneration. More so, the implications of research findings for further studies are presented, while the impact of research advances on future research and other specific recommendations are added as well.
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Tan L, Cao Z, Chen H, Xie Y, Yu L, Fu C, Zhao W, Wang Y. Curcumin reduces apoptosis and promotes osteogenesis of human periodontal ligament stem cells under oxidative stress in vitro and in vivo. Life Sci 2021; 270:119125. [PMID: 33513394 DOI: 10.1016/j.lfs.2021.119125] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 01/14/2021] [Accepted: 01/19/2021] [Indexed: 12/14/2022]
Abstract
AIMS Human periodontal ligament stem cells (hPDLSCs) tether the teeth to the surrounding bone and are considered as major functional stem cells responsible for regeneration of the alveolar bone and periodontal ligament tissue. However, the outcome of stem cell regenerative therapy is affected by the survival rate and their differentiation potential of transplanted cells. This is primarily because of local oxidative stress and chronic inflammation at the transplantation site. Therefore, our study aimed to explore whether a natural antioxidant, curcumin could increase the tissue regeneration ability of transplanted hPDLSCs. MAIN METHODS A hydrogen peroxide environment and a rat cranial bone defect model were built to mimic the oxidative stress conditions in vitro and in vivo, respectively. We evaluated the effect of curcumin on oxidative status, apoptosis, mitochondrial function and osteogenic differentiation of H2O2-stimulated hPDLSCs in vitro. We also measured the effect of curcumin on cell viability and bone repair ability of transplanted hPDLSCs in vivo. KEY FINDINGS Our data showed that curcumin enhanced cell proliferation, reduced the reactive oxygen species (ROS) levels and apoptosis, maintained the standard mitochondrial structure and function, and promoted osteogenic differentiation of H2O2-stimulated hPDLSCs. The extracellular regulated protein kinases 1/2 (Erk1/2) signaling pathway was determined to be involved in the osteogenic differentiation of the H2O2-stimulated hPDLSCs. Moreover, curcumin enhanced the viability and the bone repair ability of hPDLSCs in vivo. SIGNIFICANCE Curcumin reduced apoptosis and promoted osteogenesis of the hPDLSCs under oxidative stress, and might therefore have a potential clinical use with respect to tissue regeneration.
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Affiliation(s)
- Lingping Tan
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, 56 Lingyuanxi Road, Guangzhou 510055, China
| | - Zeyuan Cao
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, 56 Lingyuanxi Road, Guangzhou 510055, China
| | - Huan Chen
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, 56 Lingyuanxi Road, Guangzhou 510055, China
| | - Yunyi Xie
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, 56 Lingyuanxi Road, Guangzhou 510055, China
| | - Le Yu
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, 56 Lingyuanxi Road, Guangzhou 510055, China
| | - Chuanqiang Fu
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, 56 Lingyuanxi Road, Guangzhou 510055, China
| | - Wei Zhao
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, 56 Lingyuanxi Road, Guangzhou 510055, China.
| | - Yan Wang
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, 56 Lingyuanxi Road, Guangzhou 510055, China.
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Soto J, Ding X, Wang A, Li S. Neural crest-like stem cells for tissue regeneration. Stem Cells Transl Med 2021; 10:681-693. [PMID: 33533168 PMCID: PMC8046096 DOI: 10.1002/sctm.20-0361] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 12/18/2020] [Accepted: 12/24/2020] [Indexed: 12/13/2022] Open
Abstract
Neural crest stem cells (NCSCs) are a transient population of cells that arise during early vertebrate development and harbor stem cell properties, such as self‐renewal and multipotency. These cells form at the interface of non‐neuronal ectoderm and neural tube and undergo extensive migration whereupon they contribute to a diverse array of cell and tissue derivatives, ranging from craniofacial tissues to cells of the peripheral nervous system. Neural crest‐like stem cells (NCLSCs) can be derived from pluripotent stem cells, placental tissues, adult tissues, and somatic cell reprogramming. NCLSCs have a differentiation capability similar to NCSCs, and possess great potential for regenerative medicine applications. In this review, we present recent developments on the various approaches to derive NCLSCs and the therapeutic application of these cells for tissue regeneration.
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Affiliation(s)
- Jennifer Soto
- Department of Bioengineering, University of California Los Angeles, Los Angeles, California, USA
| | - Xili Ding
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, People's Republic of China
| | - Aijun Wang
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, California, USA.,Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, California, USA.,Department of Biomedical Engineering, University of California Davis, Davis, California, USA
| | - Song Li
- Department of Bioengineering, University of California Los Angeles, Los Angeles, California, USA.,Department of Medicine, University of California Los Angeles, Los Angeles, California, USA
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Rizzo S, Padelli F, Rinaldi E, Gioeni D, Aquino D, Brizzola S, Acocella F, Spaggiari L, Baggi F, Bellomi M, Bruzzone MG, Petrella F. 7-T MRI tracking of mesenchymal stromal cells after lung injection in a rat model. Eur Radiol Exp 2020; 4:54. [PMID: 33029694 PMCID: PMC7541802 DOI: 10.1186/s41747-020-00183-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 08/04/2020] [Indexed: 01/01/2023] Open
Abstract
Background Mesenchymal stromal cells (MSCs) are able to migrate and engraft at sites of inflammation, injuries, and tumours, but little is known about their fate after local injection. The purpose of this study is to perform MSC tracking, combining in vivo 7-T magnetic resonance imaging (MRI) and histological assessment, following lung injection in a rat model. Methods Five lungs were injected with ferumoxide-labelled MSCs and five with perfluorocarbon-labelled MSCs and underwent 7-T MRI. MRI acquisitions were recorded immediately (T0), at 24 h (T24) and/or 48 h (T48) after injection. For each rat, labelled cells were assessed in the main organs by MRI. Target organs were harvested under sterile conditions from rats sacrificed 0, 24, or 48 h after injection and fixed for histological analysis via confocal and structured illumination microscopy. Results Ferumoxide-labelled MSCs were not detectable in the lungs, whereas they were not visible in the distant sites. Perfluorocarbon-labelled MSCs were seen in 5/5 injected lungs at T0, in 1/2 at T24, and in 1/3 at T48. The fluorine signal in the liver was seen in 3/5 at T0, in 1/2 at T24, and in 2/3 at T48. Post-mortem histology confirmed the presence of MSCs in the injected lung. Conclusions Ferumoxide-labelled cells were not seen at distant sites; a linear decay of injected perfluorocarbon-labelled MSCs was observed at T0, T24, and T48 in the lung. In more than half of the experiments, perfluorocarbon-labelled MSCs scattering to the liver was observed, with a similar decay over time as observed in the lung.
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Affiliation(s)
- Stefania Rizzo
- Imaging Institute of the Southern Switzerland (IIMSI), Ente Ospedaliero Cantonale (EOC), via Tesserete 46, 6900, Lugano, Switzerland. .,Facoltà di Scienze biomediche, Università della Svizzera italiana (USI), Via G. Buffi 13, 6904, Lugano, Switzerland. .,Clinica di Radiologia EOC, Istituto di Imaging della Svizzera Italiana (IIMSI), via Tesserete 46, 6900, Lugano, Switzerland.
| | - Francesco Padelli
- Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Elena Rinaldi
- Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Daniela Gioeni
- Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Milan, Italy
| | - Domenico Aquino
- Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Stefano Brizzola
- Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Milan, Italy
| | - Fabio Acocella
- Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Milan, Italy
| | - Lorenzo Spaggiari
- Department of Thoracic Surgery, IRCCS European Institute of Oncology, Milan, Italy.,Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
| | - Fulvio Baggi
- Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Massimo Bellomi
- Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.,Department of Radiology, IRCCS European Institute of Oncology, Milan, Italy
| | - Maria Grazia Bruzzone
- Department of Neuroradiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Francesco Petrella
- Department of Thoracic Surgery, IRCCS European Institute of Oncology, Milan, Italy.,Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.,CRC StaMeTec Università degli studi di Milano, Milan, Italy
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Nucci MP, Filgueiras IS, Ferreira JM, de Oliveira FA, Nucci LP, Mamani JB, Rego GNA, Gamarra LF. Stem cell homing, tracking and therapeutic efficiency evaluation for stroke treatment using nanoparticles: A systematic review. World J Stem Cells 2020; 12:381-405. [PMID: 32547686 PMCID: PMC7280869 DOI: 10.4252/wjsc.v12.i5.381] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 04/02/2020] [Accepted: 04/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Stroke is the second leading cause of death worldwide. There is a real need to develop treatment strategies for reducing neurological deficits in stroke survivors, and stem cell (SC) therapeutics appear to be a promising alternative for stroke therapy that can be used in combination with approved thrombolytic or thrombectomy approaches. However, the efficacy of SC therapy depends on the SC homing ability and engraftment into the injury site over a long period of time. Nonetheless, tracking SCs from their niche to the target tissues is a complex process.
AIM To evaluate SC migration homing, tracking and therapeutic efficacy in the treatment of stroke using nanoparticles
METHODS A systematic literature search was performed to identify articles published prior to November 2019 that were indexed in PubMed and Scopus. The following inclusion criteria were used: (1) Studies that used in vivo models of stroke or ischemic brain lesions; (2) Studies of SCs labeled with some type of contrast agent for cell migration detection; and (3) Studies that involved in vivo cellular homing and tracking analysis.
RESULTS A total of 82 articles were identified by indexing in Scopus and PubMed. After the inclusion criteria were applied, 35 studies were selected, and the articles were assessed for eligibility; ultimately, only 25 studies were included. Most of the selected studies used SCs from human and mouse bone marrow labeled with magnetic nanoparticles alone or combined with fluorophore dyes. These cells were administered in the stroke model (to treat middle cerebral artery occlusion in 74% of studies and for photothrombotic induction in 26% of studies). Fifty-three percent of studies used xenogeneic grafts for cell therapy, and the migration homing and tracking evaluation was performed by magnetic resonance imaging as well as other techniques, such as near-infrared fluorescence imaging (12%) or bioluminescence assays (12%).
CONCLUSION Our systematic review provided an up-to-date evaluation of SC migration homing and the efficacy of cellular therapy for stroke treatment in terms of functional and structural improvements in the late stage.
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Affiliation(s)
- Mariana Penteado Nucci
- LIM44, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05529-060, Brazil
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Oliveira FA, Nucci MP, Filgueiras IS, Ferreira JM, Nucci LP, Mamani JB, Alvieri F, Souza LEB, Rego GNA, Kondo AT, Hamerschlak N, Gamarra LF. Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model. Cells 2020; 9:cells9040939. [PMID: 32290257 PMCID: PMC7226958 DOI: 10.3390/cells9040939] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/31/2020] [Accepted: 04/03/2020] [Indexed: 12/11/2022] Open
Abstract
The hematopoietic stem cell engraftment depends on adequate cell numbers, their homing, and the subsequent short and long-term engraftment of these cells in the niche. We performed a systematic review of the methods employed to track hematopoietic reconstitution using molecular imaging. We searched articles indexed, published prior to January 2020, in PubMed, Cochrane, and Scopus with the following keyword sequences: (Hematopoietic Stem Cell OR Hematopoietic Progenitor Cell) AND (Tracking OR Homing) AND (Transplantation). Of 2191 articles identified, only 21 articles were included in this review, after screening and eligibility assessment. The cell source was in the majority of bone marrow from mice (43%), followed by the umbilical cord from humans (33%). The labeling agent had the follow distribution between the selected studies: 14% nanoparticle, 29% radioisotope, 19% fluorophore, 19% luciferase, and 19% animal transgenic. The type of graft used in the studies was 57% allogeneic, 38% xenogeneic, and 5% autologous, being the HSC receptor: 57% mice, 9% rat, 19% fish, 5% for dog, porcine and salamander. The imaging technique used in the HSC tracking had the following distribution between studies: Positron emission tomography/single-photon emission computed tomography 29%, bioluminescence 33%, fluorescence 19%, magnetic resonance imaging 14%, and near-infrared fluorescence imaging 5%. The efficiency of the graft was evaluated in 61% of the selected studies, and before one month of implantation, the cell renewal was very low (less than 20%), but after three months, the efficiency was more than 50%, mainly in the allogeneic graft. In conclusion, our review showed an increase in using noninvasive imaging techniques in HSC tracking using the bone marrow transplant model. However, successful transplantation depends on the formation of engraftment, and the functionality of cells after the graft, aspects that are poorly explored and that have high relevance for clinical analysis.
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Affiliation(s)
- Fernando A. Oliveira
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.A.O.); (I.S.F.); (J.M.F.); (J.B.M.); (F.A.); (G.N.A.R.); (A.T.K.); (N.H.)
| | - Mariana P. Nucci
- LIM44—Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-903, Brazil;
| | - Igor S. Filgueiras
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.A.O.); (I.S.F.); (J.M.F.); (J.B.M.); (F.A.); (G.N.A.R.); (A.T.K.); (N.H.)
| | - João M. Ferreira
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.A.O.); (I.S.F.); (J.M.F.); (J.B.M.); (F.A.); (G.N.A.R.); (A.T.K.); (N.H.)
| | - Leopoldo P. Nucci
- Centro Universitário do Planalto Central, Brasília DF 72445-020, Brazil;
| | - Javier B. Mamani
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.A.O.); (I.S.F.); (J.M.F.); (J.B.M.); (F.A.); (G.N.A.R.); (A.T.K.); (N.H.)
| | - Fernando Alvieri
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.A.O.); (I.S.F.); (J.M.F.); (J.B.M.); (F.A.); (G.N.A.R.); (A.T.K.); (N.H.)
| | - Lucas E. B. Souza
- Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto SP 14049-900, Brazil;
| | - Gabriel N. A. Rego
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.A.O.); (I.S.F.); (J.M.F.); (J.B.M.); (F.A.); (G.N.A.R.); (A.T.K.); (N.H.)
| | - Andrea T. Kondo
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.A.O.); (I.S.F.); (J.M.F.); (J.B.M.); (F.A.); (G.N.A.R.); (A.T.K.); (N.H.)
| | - Nelson Hamerschlak
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.A.O.); (I.S.F.); (J.M.F.); (J.B.M.); (F.A.); (G.N.A.R.); (A.T.K.); (N.H.)
| | - Lionel F. Gamarra
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.A.O.); (I.S.F.); (J.M.F.); (J.B.M.); (F.A.); (G.N.A.R.); (A.T.K.); (N.H.)
- Correspondence: ; Tel.: +55-11-2151-0243
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Lotus seedpod-inspired hydrogels as an all-in-one platform for culture and delivery of stem cell spheroids. Biomaterials 2019; 225:119534. [DOI: 10.1016/j.biomaterials.2019.119534] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 09/05/2019] [Accepted: 09/28/2019] [Indexed: 01/01/2023]
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Xie P, Hu X, Li D, Xie S, Zhou Z, Meng X, Shan H. Bioluminescence Imaging of Transplanted Mesenchymal Stem Cells by Overexpression of Hepatocyte Nuclear Factor4α: Tracking Biodistribution and Survival. Mol Imaging Biol 2019; 21:44-53. [PMID: 29761416 DOI: 10.1007/s11307-018-1204-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
PURPOSE The purposes of this study were to construct immortalized human bone marrow mesenchymal stem cells (UE7T-13) with overexpression of the hepatocyte nuclear factor4α (hHNF4α) and luciferase2-mKate2 dual-fusion reporter gene, further investigate their impact on treating acute liver injury (ALI) in rats, and track their biodistribution and survival by bioluminescence imaging (BLI). PROCEDURES The hHNF4α and luciferase2-mKate2 genes were transduced by a lentiviral vector into UE7T-13 cells (named E7-hHNF4α-R cells), and expression was verified by immunofluorescence, RT-PCR, and flow cytometry. E7-hGFP-R cells expressing the luciferase2-mKate2/hGFP gene served as a negative group. A correlation between the bioluminescence signal and cell number was detected by BLI. The ALI rats were established and divided into three groups: PBS, E7-hGFP-R, and E7-hHNF4α-R. After transplantation of 2.0 × 106 cells, BLI was used to dynamically track their biodistribution and survival. The restoration of biological functions was assessed by serum biochemical and histological analyses. RESULTS Stable high-level expression of hHNF4α and mKate2 protein was established in the E7-hHNF4α-R cells in vitro. The E7-hHNF4α-R cells strongly expressed hGFP, hHNF4α, and mKate2 proteins, and the hHNF4α gene. hGFP-mKate2 dual-positive cell expression reached approximately 93 %. BLI verified that a linear relationship existed between the cell number and bioluminescence signal (R2 = 0.9991). The cells improved liver function in vivo after transplantation into the ALI rat liver, as evidenced by the fact that AST and ALT temporarily returned to normal levels in the recipient ALI rats. The presence of the transplanted E7-hGFP-R and E7-hHNF4α-R cells in recipient rat livers was confirmed by BLI and immunohistochemistry. However, the cells were cleared by the immune system a short time after transplantation into ALI rats with a normal immune system. CONCLUSION Our data revealed that the E7-hHNF4α-R cells can transiently improve damaged liver function and were rapidly cleared by the immune system. In addition, BLI is a useful tool to track transplanted cell biodistribution and survival.
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Affiliation(s)
- Peiyi Xie
- Guang Dong Provincial Engineering Research Center of Molecular Imaging, Zhuhai, China.,Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaojun Hu
- Guang Dong Provincial Engineering Research Center of Molecular Imaging, Zhuhai, China.,Interventional Medicine Department, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.,Interventional Radiology Institute, Sun Yat-sen University, Zhuhai, China
| | - Dan Li
- Guang Dong Provincial Engineering Research Center of Molecular Imaging, Zhuhai, China.,Interventional Medicine Department, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.,Interventional Radiology Institute, Sun Yat-sen University, Zhuhai, China
| | - Sidong Xie
- The Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhiyang Zhou
- Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaochun Meng
- Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Hong Shan
- Guang Dong Provincial Engineering Research Center of Molecular Imaging, Zhuhai, China. .,Interventional Medicine Department, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. .,Interventional Radiology Institute, Sun Yat-sen University, Zhuhai, China.
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13
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Zhong Y, Wang J, Lv W, Xu J, Mei S, Shan A. LncRNA TTN-AS1 drives invasion and migration of lung adenocarcinoma cells via modulation of miR-4677-3p/ZEB1 axis. J Cell Biochem 2019; 120:17131-17141. [PMID: 31173403 DOI: 10.1002/jcb.28973] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 03/25/2019] [Accepted: 04/12/2019] [Indexed: 12/28/2022]
Abstract
Lung adenocarcinoma is the most prevalent type of lung cancer with a high incidence and mortality worldwide. Metastasis is the major cause of high death rate in lung cancer and the potential mechanism of lung adenocarcinoma metastasis remains indistinct. Emerging investigations have demonstrated that long noncoding RNA is a kind of non-protein coding RNA and plays a critical role in cancer progression and metastasis. TTN antisense RNA 1 (TTN-AS1) has been reported to promote cell growth and metastasis in cancer. However, the function of TTN-AS1 in lung adenocarcinoma is still to be illustrated. In this study, we observed that TTN-AS1 was upregulated in tissues and cells of lung adenocarcinoma and associated with poor overall survival. TTN-AS1 promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition in lung cancer. TTN-AS1 directly bound with miR-4677-3p and negatively regulated miR-4677-3p. MiR-4677-3p rescued the inhibitive impacts of TTN-AS1 knockdown on lung adenocarcinoma. Furthermore, zinc finger E-box binding homeobox 1 (ZEB1) was the target of miR-4677-3p, and TTN-AS1 modulated ZEB1 by competing for miR-4677-3p. TTN-AS1 drove the invasion and migration of lung adenocarcinoma cells by targeting the miR-4677-3p/ZEB1 axis. To sum up, our study offers insights into the mechanism of TTN-AS1 in lung adenocarcinoma metastasis and targeting the TTN-AS1/miR-4677-3p/ZEB1 axis may be the potential innovate therapeutic strategy for the patients with lung adenocarcinoma.
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Affiliation(s)
- Yuanbo Zhong
- Emergency Department, Shenzhen People's Hospital, The Second Medical College of Jinan University, Shenzhen, Guangdong, China
| | - Jin Wang
- Emergency Department, Shenzhen People's Hospital, The Second Medical College of Jinan University, Shenzhen, Guangdong, China
| | - Wen Lv
- Emergency Department, Shenzhen People's Hospital, The Second Medical College of Jinan University, Shenzhen, Guangdong, China
| | - Jianzhong Xu
- Emergency Department, Shenzhen People's Hospital, The Second Medical College of Jinan University, Shenzhen, Guangdong, China
| | - Shanshan Mei
- Emergency Department, Shenzhen People's Hospital, The Second Medical College of Jinan University, Shenzhen, Guangdong, China
| | - Aijun Shan
- Emergency Department, Shenzhen People's Hospital, The Second Medical College of Jinan University, Shenzhen, Guangdong, China
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14
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New Strategies and In Vivo Monitoring Methods for Stem Cell-Based Anticancer Therapies. Stem Cells Int 2018; 2018:7315218. [PMID: 30581474 PMCID: PMC6276456 DOI: 10.1155/2018/7315218] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 10/22/2018] [Indexed: 02/06/2023] Open
Abstract
Cancer is a devastating disease and the second cause of death in the developed world. Despite significant advances in recent years, such as the introduction of targeted therapies such as receptor tyrosine kinase inhibitors and immunotherapy, current approaches are insufficient to stop the advance of the disease and many cancer types remain largely intractable. In this review, we describe the latest and most revolutionary stem cell-based approaches for the treatment of cancer. We also summarize the emerging imaging modalities being applied for monitoring anticancer stem cell therapy success and discuss the implications of these novel technologies for precision medicine.
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15
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Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery. MEDICINES 2017; 4:medicines4040087. [PMID: 29168760 PMCID: PMC5750611 DOI: 10.3390/medicines4040087] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2017] [Revised: 11/22/2017] [Accepted: 11/22/2017] [Indexed: 12/20/2022]
Abstract
Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.
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16
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Squires JE, Soltys KA, McKiernan P, Squires RH, Strom SC, Fox IJ, Soto-Gutierrez A. Clinical Hepatocyte Transplantation: What Is Next? CURRENT TRANSPLANTATION REPORTS 2017; 4:280-289. [PMID: 29732274 DOI: 10.1007/s40472-017-0165-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Purpose of review Significant recent scientific developments have occurred in the field of liver repopulation and regeneration. While techniques to facilitate liver repopulation with donor hepatocytes and different cell sources have been studied extensively in the laboratory, in recent years clinical hepatocyte transplantation (HT) and liver repopulation trials have demonstrated new disease indications and also immunological challenges that will require the incorporation of a fresh look and new experimental approaches. Recent findings Growth advantage and regenerative stimulus are necessary to allow donor hepatocytes to proliferate. Current research efforts focus on mechanisms of donor hepatocyte expansion in response to liver injury/preconditioning. Moreover, latest clinical evidence shows that important obstacles to HT include optimizing engraftment and limited duration of effectiveness, with hepatocytes being lost to immunological rejection. We will discuss alternatives for cellular rejection monitoring, as well as new modalities to follow cellular graft function and near-to-clinical cell sources. Summary HT partially corrects genetic disorders for a limited period of time and has been associated with reversal of ALF. The main identified obstacles that remain to make HT a curative approach include improving engraftment rates, and methods for monitoring cellular graft function and rejection. This review aims to discuss current state-of-the-art in clinical HT and provide insights into innovative approaches taken to overcome these obstacles.
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Affiliation(s)
- James E Squires
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States
| | - Kyle A Soltys
- Thomas E. Starzl Transplant Institute, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States
| | - Patrick McKiernan
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States
| | - Robert H Squires
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States
| | - Stephen C Strom
- Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, Stockholm, Sweden
| | - Ira J Fox
- Department of Surgery, Children's Hospital of Pittsburgh of UPMC, and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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17
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Dadashpour M, Pilehvar-Soltanahmadi Y, Zarghami N, Firouzi-Amandi A, Pourhassan-Moghaddam M, Nouri M. Emerging Importance of Phytochemicals in Regulation of Stem Cells Fate via Signaling Pathways. Phytother Res 2017; 31:1651-1668. [DOI: 10.1002/ptr.5908] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 08/01/2017] [Accepted: 08/10/2017] [Indexed: 12/13/2022]
Affiliation(s)
- Mehdi Dadashpour
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences; Tabriz University of Medical Sciences; Tabriz Iran
- Stem Cell Research Center; Tabriz University of Medical Sciences; Tabriz Iran
- Student Research Committee; Tabriz University of Medical Sciences; Tabriz Iran
| | - Younes Pilehvar-Soltanahmadi
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences; Tabriz University of Medical Sciences; Tabriz Iran
- Stem Cell Research Center; Tabriz University of Medical Sciences; Tabriz Iran
| | - Nosratollah Zarghami
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences; Tabriz University of Medical Sciences; Tabriz Iran
- Stem Cell Research Center; Tabriz University of Medical Sciences; Tabriz Iran
| | | | - Mohammad Pourhassan-Moghaddam
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences; Tabriz University of Medical Sciences; Tabriz Iran
| | - Mohammad Nouri
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences; Tabriz University of Medical Sciences; Tabriz Iran
- Stem Cell Research Center; Tabriz University of Medical Sciences; Tabriz Iran
- Stem Cell and Regenerative Medicine Institute; Tabriz University of Medical Sciences; Tabriz Iran
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18
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Gurel Pekozer G, Ramazanoglu M, Schlegel KA, Kok FN, Torun Kose G. Role of STRO-1 sorting of porcine dental germ stem cells in dental stem cell-mediated bone tissue engineering. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2017; 46:607-618. [DOI: 10.1080/21691401.2017.1332637] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Gorke Gurel Pekozer
- Molecular Biology-Genetics and Biotechnology Program, Istanbul Technical University, Istanbul, Turkey
- Genetics and Bioengineering Department, Yeditepe University, Istanbul, Turkey
- Center of Excellence in Biomaterials and Tissue Engineering, BIOMATEN, METU, Ankara, Turkey
| | - Mustafa Ramazanoglu
- Department of Oral Surgery, Faculty of Dentistry, Istanbul University, Istanbul, Turkey
| | - Karl Andreas Schlegel
- Department of Maxillofacial Surgery, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen-Nuremberg, Bavaria, Germany
| | - Fatma Nese Kok
- Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey
| | - Gamze Torun Kose
- Genetics and Bioengineering Department, Yeditepe University, Istanbul, Turkey
- Center of Excellence in Biomaterials and Tissue Engineering, BIOMATEN, METU, Ankara, Turkey
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19
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Wang Y, Wu H, Shen M, Ding S, Miao J, Chen N. Role of human amnion-derived mesenchymal stem cells in promoting osteogenic differentiation by influencing p38 MAPK signaling in lipopolysaccharide -induced human bone marrow mesenchymal stem cells. Exp Cell Res 2016; 350:41-49. [PMID: 27832946 DOI: 10.1016/j.yexcr.2016.11.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Revised: 08/15/2016] [Accepted: 11/02/2016] [Indexed: 12/29/2022]
Abstract
Periodontitis is a chronic inflammatory disease induced by bacterial pathogens, which not only affect connective tissue attachments but also cause alveolar bone loss. In this study, we investigated the anti-inflammatory effects of Human amnion-derived mesenchymal stem cells (HAMSCs) on human bone marrow mesenchymal stem cells (HBMSCs) under lipopolysaccharide (LPS)-induced inflammatory conditions. Proliferation levels were measured by flow cytometry and immunofluorescence staining of 5-ethynyl-2'-deoxyuridine (EdU). Osteoblastic differentiation and mineralization were investigated using chromogenic alkaline phosphatase activity (ALP) activity substrate assays, Alizarin red S staining, and RT-PCR analysis of HBMSCs osteogenic marker expression. Oxidative stress induced by LPS was investigated by assaying reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity. Here, we demonstrated that HAMSCs increased the proliferation, osteoblastic differentiation, and SOD activity of LPS-induced HBMSCs, and down-regulated the ROS level. Moreover, our results suggested that the activation of p38 MAPK signal transduction pathway is essential for reversing the LPS-induced bone-destructive processes. SB203580, a selective inhibitor of p38 MAPK signaling, significantly suppressed the anti-inflammatory effects in HAMSCs. In conclusion, HAMSCs show a strong potential in treating inflammation-induced bone loss by influencing p38 MAPK signaling.
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Affiliation(s)
- Yuli Wang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing 210029, Jiangsu, the People's Republic of China
| | - Hongxia Wu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing 210029, Jiangsu, the People's Republic of China
| | - Ming Shen
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing 210029, Jiangsu, the People's Republic of China
| | - Siyang Ding
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing 210029, Jiangsu, the People's Republic of China
| | - Jing Miao
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing 210029, Jiangsu, the People's Republic of China
| | - Ning Chen
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing 210029, Jiangsu, the People's Republic of China.
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