TY - JOUR
T1 - Inflammation converts human mesoangioblasts into targets of alloreactive immune responses
T2 - Implications for allogeneic cell therapy of DMD
AU - Noviello, Maddalena
AU - Tedesco, Francesco Saverio
AU - Bondanza, Attilio
AU - Tonlorenzi, Rossana
AU - Rosaria Carbone, Maria
AU - Gerli, Mattia Francesco Maria
AU - Marktel, Sarah
AU - Napolitano, Sara
AU - Cicalese, Maria Pia
AU - Ciceri, Fabio
AU - Peretti, Giuseppe
AU - Cossu, Giulio
AU - Bonini, Chiara
PY - 2014
Y1 - 2014
N2 - 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-γ 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.
AB - 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-γ 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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U2 - 10.1038/mt.2014.62
DO - 10.1038/mt.2014.62
M3 - Article
C2 - 24736278
AN - SCOPUS:84903778607
VL - 22
SP - 1342
EP - 1352
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 7
ER -