Inflammation converts human mesoangioblasts into targets of alloreactive immune responses: Implications for allogeneic cell therapy of DMD

Maddalena Noviello, Francesco Saverio Tedesco, Attilio Bondanza, Rossana Tonlorenzi, Maria Rosaria Carbone, Mattia Francesco Maria Gerli, Sarah Marktel, Sara Napolitano, Maria Pia Cicalese, Fabio Ciceri, Giuseppe Peretti, Giulio Cossu, Chiara Bonini

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 languageEnglish
Pages (from-to)1342-1352
Number of pages11
JournalMolecular Therapy
Volume22
Issue number7
DOIs
Publication statusPublished - 2014

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Cell- and Tissue-Based Therapy
Inflammation
T-Lymphocytes
Stem Cells
Immune Evasion
Serine Proteinase Inhibitors
Duchenne Muscular Dystrophy
Skeletal Muscle Fibers
Interferons
Therapeutics

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 journalArticle

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. / Inflammation converts human mesoangioblasts into targets of alloreactive immune responses : Implications for allogeneic cell therapy of DMD. In: Molecular Therapy. 2014 ; Vol. 22, No. 7. pp. 1342-1352.
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