In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia
Abstract Background Cell therapy has been proposed for patients with critical limb ischemia (CLI). Autologous bone marrow derived cells (BMCs) have been mostly used, mesenchymal stem cells (MSCs) being an alternative. The aim of this study was to characterize two types of MSCs and evaluate their eff...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12967-019-2003-3 |
| _version_ | 1818410400007323648 |
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| author | Rida Al-Rifai Philippe Nguyen Nicole Bouland Christine Terryn Lukshe Kanagaratnam Gaël Poitevin Caroline François Catherine Boisson-Vidal Marie-Antoinette Sevestre Claire Tournois |
| author_facet | Rida Al-Rifai Philippe Nguyen Nicole Bouland Christine Terryn Lukshe Kanagaratnam Gaël Poitevin Caroline François Catherine Boisson-Vidal Marie-Antoinette Sevestre Claire Tournois |
| author_sort | Rida Al-Rifai |
| collection | DOAJ |
| description | Abstract Background Cell therapy has been proposed for patients with critical limb ischemia (CLI). Autologous bone marrow derived cells (BMCs) have been mostly used, mesenchymal stem cells (MSCs) being an alternative. The aim of this study was to characterize two types of MSCs and evaluate their efficacy. Methods MSCs were obtained from CLI-patients BMCs. Stimulated- (S-) MSCs were cultured in endothelial growth medium. Cells were characterized by the expression of cell surface markers, the relative expression of 6 genes, the secretion of 10 cytokines and the ability to form vessel-like structures. The cell proangiogenic properties was analysed in vivo, in a hindlimb ischemia model. Perfusion of lower limbs and functional tests were assessed for 28 days after cell infusion. Muscle histological analysis (neoangiogenesis, arteriogenesis and muscle repair) was performed. Results S-MSCs can be obtained from CLI-patients BMCs. They do not express endothelial specific markers but can be distinguished from MSCs by their secretome. S-MSCs have the ability to form tube-like structures and, in vivo, to induce blood flow recovery. No amputation was observed in S-MSCs treated mice. Functional tests showed improvement in treated groups with a superiority of MSCs and S-MSCs. In muscles, CD31+ and αSMA+ labelling were the highest in S-MSCs treated mice. S-MSCs induced the highest muscle repair. Conclusions S-MSCs exert angiogenic potential probably mediated by a paracrine mechanism. Their administration is associated with flow recovery, limb salvage and muscle repair. The secretome from S-MSCs or secretome-derived products may have a strong potential in vessel regeneration and muscle repair. Trial registration NCT00533104 |
| first_indexed | 2024-12-14T10:14:55Z |
| format | Article |
| id | doaj.art-f1b7f8a6db994f8ea6c2b9b287d61151 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-14T10:14:55Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-f1b7f8a6db994f8ea6c2b9b287d611512022-12-21T23:06:54ZengBMCJournal of Translational Medicine1479-58762019-08-0117112110.1186/s12967-019-2003-3In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemiaRida Al-Rifai0Philippe Nguyen1Nicole Bouland2Christine Terryn3Lukshe Kanagaratnam4Gaël Poitevin5Caroline François6Catherine Boisson-Vidal7Marie-Antoinette Sevestre8Claire Tournois9EA-3801, SFR CAP-santé, Université de Reims Champagne-ArdenneEA-3801, SFR CAP-santé, Université de Reims Champagne-ArdenneLaboratoire d’Anatomie Pathologique, Université de Reims Champagne-ArdennePlateforme PICT, Université de Reims Champagne ArdenneUnité d’aide méthodologique CHU Robert DebréEA-3801, SFR CAP-santé, Université de Reims Champagne-ArdenneEA-3801, SFR CAP-santé, Université de Reims Champagne-ArdenneInserm UMR S1140, Faculté de Pharmacie de ParisService de Médecine Vasculaire, CHUEA-3801, SFR CAP-santé, Université de Reims Champagne-ArdenneAbstract Background Cell therapy has been proposed for patients with critical limb ischemia (CLI). Autologous bone marrow derived cells (BMCs) have been mostly used, mesenchymal stem cells (MSCs) being an alternative. The aim of this study was to characterize two types of MSCs and evaluate their efficacy. Methods MSCs were obtained from CLI-patients BMCs. Stimulated- (S-) MSCs were cultured in endothelial growth medium. Cells were characterized by the expression of cell surface markers, the relative expression of 6 genes, the secretion of 10 cytokines and the ability to form vessel-like structures. The cell proangiogenic properties was analysed in vivo, in a hindlimb ischemia model. Perfusion of lower limbs and functional tests were assessed for 28 days after cell infusion. Muscle histological analysis (neoangiogenesis, arteriogenesis and muscle repair) was performed. Results S-MSCs can be obtained from CLI-patients BMCs. They do not express endothelial specific markers but can be distinguished from MSCs by their secretome. S-MSCs have the ability to form tube-like structures and, in vivo, to induce blood flow recovery. No amputation was observed in S-MSCs treated mice. Functional tests showed improvement in treated groups with a superiority of MSCs and S-MSCs. In muscles, CD31+ and αSMA+ labelling were the highest in S-MSCs treated mice. S-MSCs induced the highest muscle repair. Conclusions S-MSCs exert angiogenic potential probably mediated by a paracrine mechanism. Their administration is associated with flow recovery, limb salvage and muscle repair. The secretome from S-MSCs or secretome-derived products may have a strong potential in vessel regeneration and muscle repair. Trial registration NCT00533104http://link.springer.com/article/10.1186/s12967-019-2003-3AngiogenesisCell therapyCritical limb ischemiaMesenchymal stem cells |
| spellingShingle | Rida Al-Rifai Philippe Nguyen Nicole Bouland Christine Terryn Lukshe Kanagaratnam Gaël Poitevin Caroline François Catherine Boisson-Vidal Marie-Antoinette Sevestre Claire Tournois In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia Journal of Translational Medicine Angiogenesis Cell therapy Critical limb ischemia Mesenchymal stem cells |
| title | In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia |
| title_full | In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia |
| title_fullStr | In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia |
| title_full_unstemmed | In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia |
| title_short | In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia |
| title_sort | in vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia |
| topic | Angiogenesis Cell therapy Critical limb ischemia Mesenchymal stem cells |
| url | http://link.springer.com/article/10.1186/s12967-019-2003-3 |
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