Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1342-1352 |
| Number of pages | 11 |
| Journal | Molecular Therapy |
| Volume | 22 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2014 |
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ASJC Scopus subject areas
- Molecular Biology
- Molecular Medicine
- Genetics
- Drug Discovery
- Pharmacology
- Medicine(all)
Cite this
Inflammation converts human mesoangioblasts into targets of alloreactive immune responses : Implications for allogeneic cell therapy of DMD. / Noviello, Maddalena; Tedesco, Francesco Saverio; Bondanza, Attilio; Tonlorenzi, Rossana; Rosaria Carbone, Maria; Gerli, Mattia Francesco Maria; Marktel, Sarah; Napolitano, Sara; Cicalese, Maria Pia; Ciceri, Fabio; Peretti, Giuseppe; Cossu, Giulio; Bonini, Chiara.
In: Molecular Therapy, Vol. 22, No. 7, 2014, p. 1342-1352.Research output: Contribution to journal › Article
}
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 -