Journal
MOLECULAR THERAPY
Volume 22, Issue 7, Pages 1342-1352Publisher
CELL PRESS
DOI: 10.1038/mt.2014.62
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Funding
- Italian Ministry of Health [GR07-5 BO, RO10/07-B-1]
- Italian Ministry of Research and University (FIRB-IDEAS)
- Fondazione Cariplo
- Telethon [GGP08030]
- EU-FP7 program (ATTACK)
- EU-FP7 program (PERSIST)
- EU-FP7 program (SUPERSIST)
- EU-FP7 program (OPTISTEM)
- Regione Piemonte, Direzione Sanita Settore Promozione della Salute e Interventi di Prevenzione Individuale e Collettiva
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Stem cell therapy is a promising approach to regenerate healthy tissues starting from a limited amount of self-renewing cells. Immunological rejection of cell therapy products might represent a major limitation. In this study, we investigated the immunological functional profile of mesoangioblasts, vessel-associated myogenic stem cells, currently tested in a phase 1-2a trial, active in our Institute, for the treatment of Duchenne muscular dystrophy. We report that in resting conditions, human mesoangioblasts are poorly immunogenic, inefficient in promoting the expansion of alloreactive T cells and intrinsically resistant to T-cell killing. However, upon exposure to interferon-gamma or differentiation into myotubes, mesoangioblasts acquire the ability to promote the expansion of alloreactive T cells and acquire sensitivity to T-cell killing. Resistance of mesoangioblasts to T-cell killing is largely due to the expression of the intracellular serine protease inhibitor-9 and represents a relevant mechanism of stem cell immune evasion.
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