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Bone Marrow Mesenchymal Stem Cells in Acute-on-Chronic Liver Failure Grades 2 and 3: A Phase I-II Randomized Clinical Trial. Can J Gastroenterol Hepatol 2021; 2021:3662776. [PMID: 34395335 PMCID: PMC8357501 DOI: 10.1155/2021/3662776] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 07/24/2021] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Acute-on-chronic liver failure (ACLF) is an acute liver decompensation in cirrhotic patients, which leads to organ failures and high short-term mortality. The treatment is based on the management of complications and, in severe cases, liver transplantation. Since specific treatment is unavailable, we aimed to evaluate the safety and initial efficacy of bone marrow mesenchymal stem cells (BM-MSC) in patients with ACLF Grades 2 and 3, a population excluded from previous clinical trials. METHODS This is a randomized placebo-controlled phase I-II single center study, which enrolled 9 cirrhotic patients from 2018 to 2020, regardless of the etiology. The control group (n = 5) was treated with standard medical therapy (SMT) and placebo infusion of saline. The intervention group (n = 4) received SMT plus 5 infusions of 1 × 106 cells/kg of BM-MSC for 3 weeks. Both groups were monitored for 90 days. A Chi-square test was used for qualitative variables, and the t-test and Mann-Whitney U test for quantitative variables. The Kaplan-Meier estimator was used to build survival curves. In this study, we followed the intention-to-treat analysis, with a significance of 5%. RESULTS Nine patients with a mean Child-Pugh (CP) of 12.3, MELD of 38.4, and CLIF-C score of 50.7 were recruited. Hepatitis C and alcohol were the main etiologies. The average infusion per patient was 2.9 and only 3 patients (2 in control and 1 in the BM-MSC group) received all the protocol infusions. There were no infusion-related side effects, although one patient in the intervention group presented hypernatremia and a gastric ulcer, after the third and fifth infusions, respectively. The survival rate after 90 days was 20% (1/5) for placebo versus 25% (1/4) for the BM-MSC. The patient who completed the entire MSC protocol showed a significant improvement in CP (C-14 to B-9), MELD (32 to 22), and ACLF (grade 3 to 0). CONCLUSION BM-MSC infusion is safe and feasible in patients with ACLF Grades 2 and 3.
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Chondrogenic effect of liquid and gelled platelet lysate on canine adipose-derived mesenchymal stromal cells. Res Vet Sci 2019; 124:393-398. [PMID: 31077967 DOI: 10.1016/j.rvsc.2019.04.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Revised: 04/26/2019] [Accepted: 04/28/2019] [Indexed: 11/21/2022]
Abstract
Osteoarthritis associated with hip dysplasia is one of the most common orthopedic abnormalities in dogs, with an incidence of up to 40% in some breeds. Tissue therapy of cartilage has received great attention, with use of mesenchymal stromal cells and different types of biomaterials. The present study aimed to evaluate the effect of platelet lysate (PL) on the proliferation and differentiation of canine adipose tissue-derived mesenchymal stromal cells (ASCs), in liquid culture or hydrogels. PL was prepared from blood collected from healthy dogs and submitted to freezing-thawing cycles, and hydrogel was formed with canine thrombin. The effect of PL on the proliferation and differentiation of canine ASCs was evaluated in liquid and hydrogel systems, with microscopy, quantification of dsDNA, histology and quantification of glycosaminoglycans. The addition of 5% or 10% PL to the culture medium induced a greater proliferation rate than the presence of 10% fetal bovine serum. The cultivation of ASCs in PL gel, with normal or chondrogenic medium, resulted in maintenance of proliferation level similar to the conventional 2D cultivation, and induction of chondrogenic differentiation, especially in the presence of the chondrogenesis induction medium.
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Zamani M, Yaghoubi Y, Movassaghpour A, Shakouri K, Mehdizadeh A, Pishgahi A, Yousefi M. Novel therapeutic approaches in utilizing platelet lysate in regenerative medicine: Are we ready for clinical use? J Cell Physiol 2019; 234:17172-17186. [PMID: 30912141 DOI: 10.1002/jcp.28496] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 02/18/2019] [Accepted: 02/20/2019] [Indexed: 12/13/2022]
Abstract
Hemoderivative materials are used to treat different diseases. These derivatives include platelet-rich plasma, serum, platelet gel, and platelet lysate (PL). Among them, PL contains more growth factors than the others and its production is inexpensive and easy. PL is one of the proper sources of platelet release factors. It is used in cells growth and proliferation and is a good alternative to fetal bovine serum. In recent years, the clinical use of PL has gained more appeal by scientists. PL is a solution saturated by growth factors, proteins, cytokines, and chemokines and is administered to treat different diseases such as wound healing, bone regeneration, alopecia, oral mucositis, radicular pain, osteoarthritis, and ocular diseases. In addition, it can be used in cell culture for cell therapy and tissue transplantation purposes. Platelet-derived growth factor, fibroblast growth factor, insulin-like growth factor, transforming growth factor β, and vascular endothelial growth factor are key PL growth factors playing a major role in cell proliferation, wound healing, and angiogenesis. In this paper, we scrutinized recent advances in using PL and PL-derived growth factors to treat diseases and in regenerative medicine, and the ability to replace PL with other hemoderivative materials.
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Affiliation(s)
- Majid Zamani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yoda Yaghoubi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aliakbar Movassaghpour
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Hematology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Kazem Shakouri
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Mehdizadeh
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Pishgahi
- Department of Hematology, Tabriz University of Medical Sciences, Tabriz, Iran.,Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran
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Seng A, Dunavin N. Mesenchymal stromal cell infusions for acute graft-versus-host disease: Rationale, data, and unanswered questions. ACTA ACUST UNITED AC 2018. [DOI: 10.1002/acg2.14] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Amara Seng
- Department of Microbiology; Molecular Genetics and Immunology; University of Kansas Medical Center; Kansas City Kansas
| | - Neil Dunavin
- Division of Hematological Malignancies and Cellular Therapeutics; Department of Internal Medicine; University of Kansas Medical Center; Kansas City Kansas
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Han N, Xiao Y. [Research status and application prospect of mesenchymal stem cells in hematological diseases]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2018; 39:346-349. [PMID: 29779338 PMCID: PMC7342131 DOI: 10.3760/cma.j.issn.0253-2727.2018.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Indexed: 11/07/2022]
Affiliation(s)
| | - Y Xiao
- Department of Hematology, Guangzhou General Hospital of Guangzhou Military Command of PLA, Southern Medical University, Guangdong 510010, China
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Baggio L, Laureano ÁM, Silla LMDR, Lee DA. Natural killer cell adoptive immunotherapy: Coming of age. Clin Immunol 2017; 177:3-11. [DOI: 10.1016/j.clim.2016.02.003] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 02/06/2016] [Accepted: 02/09/2016] [Indexed: 11/26/2022]
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Zorzopulos J, Opal SM, Hernando-Insúa A, Rodriguez JM, Elías F, Fló J, López RA, Chasseing NA, Lux-Lantos VA, Coronel MF, Franco R, Montaner AD, Horn DL. Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy. World J Stem Cells 2017; 9:45-67. [PMID: 28396715 PMCID: PMC5368622 DOI: 10.4252/wjsc.v9.i3.45] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 10/12/2016] [Accepted: 12/19/2016] [Indexed: 02/06/2023] Open
Abstract
The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.
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Astori G, Amati E, Bambi F, Bernardi M, Chieregato K, Schäfer R, Sella S, Rodeghiero F. Platelet lysate as a substitute for animal serum for the ex-vivo expansion of mesenchymal stem/stromal cells: present and future. Stem Cell Res Ther 2016; 7:93. [PMID: 27411942 PMCID: PMC4944312 DOI: 10.1186/s13287-016-0352-x] [Citation(s) in RCA: 133] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The use of fetal bovine serum (FBS) as a cell culture supplement is discouraged by regulatory authorities to limit the risk of zoonoses and xenogeneic immune reactions in the transplanted host. Additionally, FBS production came under scrutiny due to animal welfare concerns. Platelet derivatives have been proposed as FBS substitutes for the ex-vivo expansion of mesenchymal stem/stromal cells (MSCs) since platelet-derived growth factors can promote MSC ex-vivo expansion. Platelet-derived growth factors are present in platelet lysate (PL) obtained after repeated freezing–thawing cycles of the platelet-rich plasma or by applying physiological stimuli such as thrombin or CaCl2. PL-expanded MSCs have been used already in the clinic, taking advantage of their faster proliferation compared with FBS-expanded preparations. Should PL be applied to other biopharmaceutical products, its demand is likely to increase dramatically. The use of fresh platelet units for the production of PL raises concerns due to limited availability of platelet donors. Expired units might represent an alternative, but further data are needed to define safety, including pathogen reduction, and functionality of the obtained PL. In addition, relevant questions concerning the definition of PL release criteria, including concentration ranges of specific growth factors in PL batches for various clinical indications, also need to be addressed. We are still far from a common definition of PL and standardized PL manufacture due to our limited knowledge of the mechanisms that mediate PL-promoting cell growth. Here, we concisely discuss aspects of PL as MSC culture supplement as a preliminary step towards an agreed definition of the required characteristics of PL for the requirements of manufacturers and users.
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Affiliation(s)
- Giuseppe Astori
- Advanced Cellular Therapy Laboratory, Department of Cellular Therapy and Hematology, San Bortolo Hospital, Via Rodolfi 37, 36100, Vicenza, Italy.
| | - Eliana Amati
- Advanced Cellular Therapy Laboratory, Department of Cellular Therapy and Hematology, San Bortolo Hospital, Via Rodolfi 37, 36100, Vicenza, Italy
| | - Franco Bambi
- Transfusion Medicine and Cell Therapy, "A. Meyer" University Children's Hospital, Florence, Italy
| | - Martina Bernardi
- Advanced Cellular Therapy Laboratory, Department of Cellular Therapy and Hematology, San Bortolo Hospital, Via Rodolfi 37, 36100, Vicenza, Italy.,Hematology Project Foundation, Contrà S. Francesco 41, Vicenza, Italy
| | - Katia Chieregato
- Advanced Cellular Therapy Laboratory, Department of Cellular Therapy and Hematology, San Bortolo Hospital, Via Rodolfi 37, 36100, Vicenza, Italy.,Hematology Project Foundation, Contrà S. Francesco 41, Vicenza, Italy
| | - Richard Schäfer
- Department of Cell Therapeutics & Cell Processing, Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service, Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Sandhofstrasse 1, Frankfurt am Main, Germany
| | - Sabrina Sella
- Advanced Cellular Therapy Laboratory, Department of Cellular Therapy and Hematology, San Bortolo Hospital, Via Rodolfi 37, 36100, Vicenza, Italy
| | - Francesco Rodeghiero
- Advanced Cellular Therapy Laboratory, Department of Cellular Therapy and Hematology, San Bortolo Hospital, Via Rodolfi 37, 36100, Vicenza, Italy.,Hematology Project Foundation, Contrà S. Francesco 41, Vicenza, Italy
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Wang L, Wang HX, Zhu L, Zheng XL, Wang ZD, Yan HM, Ding L, Han DM. [Efficacy and security of matched unrelated donor hematopoietic stem cell transplant with transfusion of multipotent mesenchymal cells in pediatric severe aplastic anemia]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2016; 37:453-7. [PMID: 27431066 PMCID: PMC7348345 DOI: 10.3760/cma.j.issn.0253-2727.2016.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Indexed: 11/08/2022]
Abstract
OBJECTIVE To observe the efficacy of matched unrelated donor hematopoietic stem cell transplant (HSCT) with transfusion of multipotent mesenchymal cells (MSC) in pediatric severe aplastic anemia (SAA). METHODS 19 children with SAA received matched unrelated donor HSCT with MSC, and the hematopoietic recovery and transplant-associated complications of these children were monitored. RESULTS All patients achieved rapid hematopoietic reconstruction after HSCT, and the median durations to neutrophil and platelet recovery were 12 (9-21) days and 14 (8-24) days respectively, but delayed rejection occurred in one case four months after HSCT. 9 cases developed grade Ⅰ acute graft-versus-host (aGVHD), and one case grade Ⅲ aGVHD and diffuse chronic graft-versus-host. Cytomegalovirus viremias were observed in 15 patients. 2 cases developed hemorrhagic cystitis, 10 children experienced infections. All the children were alive during a median following-up time of 27(8-70) months, one of them developed LPD and received rituximab and chemotherapy, delayed rejection occurred in this patient four months after HSCT, Haplo-identical HSCT from his father as the donor was performed and achieved successful engraftment. CONCLUSION The matched unrelated donor HSCT with MSC in pediatric SAA was safe and effective.
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Affiliation(s)
- L Wang
- Department of Hematology, the Air Force General Hospital, PLA, Beijing 100142, China
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Rodrigues F, Pezzi A, Laureano Á, Valim V, Zambonato B, Dahmer A, Baggio L, Sehn F, Wilke I, L. da Silva MA, Amorin B. Adipocyte Derived Mesenchymal Stromal Cell and Platelet Lysate: Ideal Cell and Supplement for the Treatment of Immune-Inflammatory Diseases? Cell 2016. [DOI: 10.4236/cellbio.2016.52002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Tavakolinejad S, Khosravi M, Mashkani B, Ebrahimzadeh Bideskan A, Sanjar Mossavi N, Parizadeh MRS, Hamidi Alamdari D. The effect of human platelet-rich plasma on adipose-derived stem cell proliferation and osteogenic differentiation. IRANIAN BIOMEDICAL JOURNAL 2015; 18:151-157. [PMID: 24842141 PMCID: PMC4048479 DOI: 10.6091/ibj.1301.2014] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The cultured mesenchymal stem cells (MSC) have been used in many clinical trials; however, there are still some concerns about the cultural conditions. One concern is related to the use of FBS as a widely used xenogeneic supplement in the culture system. Human platelet-rich plasma (hPRP) is a candidate replacement for FBS. In this study, the effect of hPRP on MSC proliferation and osteogenic differentiation has been evaluated. METHODS Human adipose-derived stem cells (hADSC) were expanded. Cells from the third passage were characterized by flow cytometric analysis and used for in vitro experiments. Resazurin and alizarin red stains were used for cell proliferation and osteogenic differentiation assays, respectively. RESULTS Treatment with hPRP resulted in a statistically significant increase in cell proliferation compare to the negative control group (P<0.001). Cell proliferation in the 15% hPRP group was also significantly higher than that in the 10% hPRP group (P<0.05). Additionally, it caused less osteogenic differentiation of the hADSC compared to the FBS (P<0.001), but in comparison to negative control, it caused acceptable mineralization (P<0.001). CONCLUSION These findings indicate that hPRP not only improves the proliferation but also it can be a suitable substitution in osteogenic differentiation for clinical purposes. However, the clinical application value of hPRP still needs more investigation.
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Affiliation(s)
- Sima Tavakolinejad
- Dept. of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Khosravi
- Dept. of Clinical Biochemistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Baratali Mashkani
- Dept. of Clinical Biochemistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | | | | | - Daryoush Hamidi Alamdari
- Stem cell and Regenerative Medicine Research Group, Biochemistry and Nutrition Research Center, Dept. of Clinical Biochemistry, School of Medicine,
Mashhad University of Medical Sciences, Mashhad, Iran
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Zhu L, Wang Z, Zheng X, Ding L, Han D, Yan H, Guo Z, Wang H. Haploidentical hematopoietic stem cell transplant with umbilical cord-derived multipotent mesenchymal cell infusion for the treatment of high-risk acute leukemia in children. Leuk Lymphoma 2014; 56:1346-52. [DOI: 10.3109/10428194.2014.939970] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Murray IR, West CC, Hardy WR, James AW, Park TS, Nguyen A, Tawonsawatruk T, Lazzari L, Soo C, Péault B. Natural history of mesenchymal stem cells, from vessel walls to culture vessels. Cell Mol Life Sci 2014; 71:1353-74. [PMID: 24158496 PMCID: PMC11113613 DOI: 10.1007/s00018-013-1462-6] [Citation(s) in RCA: 197] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2013] [Revised: 08/17/2013] [Accepted: 08/23/2013] [Indexed: 02/06/2023]
Abstract
Mesenchymal stem/stromal cells (MSCs) can regenerate tissues by direct differentiation or indirectly by stimulating angiogenesis, limiting inflammation, and recruiting tissue-specific progenitor cells. MSCs emerge and multiply in long-term cultures of total cells from the bone marrow or multiple other organs. Such a derivation in vitro is simple and convenient, hence popular, but has long precluded understanding of the native identity, tissue distribution, frequency, and natural role of MSCs, which have been defined and validated exclusively in terms of surface marker expression and developmental potential in culture into bone, cartilage, and fat. Such simple, widely accepted criteria uniformly typify MSCs, even though some differences in potential exist, depending on tissue sources. Combined immunohistochemistry, flow cytometry, and cell culture have allowed tracking the artifactual cultured mesenchymal stem/stromal cells back to perivascular anatomical regions. Presently, both pericytes enveloping microvessels and adventitial cells surrounding larger arteries and veins have been described as possible MSC forerunners. While such a vascular association would explain why MSCs have been isolated from virtually all tissues tested, the origin of the MSCs grown from umbilical cord blood remains unknown. In fact, most aspects of the biology of perivascular MSCs are still obscure, from the emergence of these cells in the embryo to the molecular control of their activity in adult tissues. Such dark areas have not compromised intents to use these cells in clinical settings though, in which purified perivascular cells already exhibit decisive advantages over conventional MSCs, including purity, thorough characterization and, principally, total independence from in vitro culture. A growing body of experimental data is currently paving the way to the medical usage of autologous sorted perivascular cells for indications in which MSCs have been previously contemplated or actually used, such as bone regeneration and cardiovascular tissue repair.
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Affiliation(s)
- Iain R. Murray
- MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
- BHF Center for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK
- Orthopedic Hospital Research Center and Broad Stem Cell Center, David Geffen School of Medicine, University of California, Los Angeles, USA
| | - Christopher C. West
- MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
- BHF Center for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Winters R. Hardy
- Orthopedic Hospital Research Center and Broad Stem Cell Center, David Geffen School of Medicine, University of California, Los Angeles, USA
- Indiana Center for Vascular Biology and Medicine, Indianapolis, USA
| | - Aaron W. James
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA
| | - Tea Soon Park
- Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, USA
| | - Alan Nguyen
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA
| | - Tulyapruek Tawonsawatruk
- MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
- BHF Center for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Lorenza Lazzari
- Cell Factory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Chia Soo
- Division of Plastic and Reconstructive Surgery, Departments of Surgery and Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, USA
| | - Bruno Péault
- MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
- BHF Center for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK
- Orthopedic Hospital Research Center and Broad Stem Cell Center, David Geffen School of Medicine, University of California, Los Angeles, USA
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