title: Inflammation converts human mesoangioblasts into targets of alloreactive immune responses: implications for allogeneic cell therapy of DMD.
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.
authors.affiliation: Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Noviello
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, UK.
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Tedesco
authors.affiliation: Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Bondanza
authors.affiliation: Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Tonlorenzi
authors.affiliation: Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Rosaria Carbone
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, UK.
authors.forename: Mattia Francesco Maria
authors.initials: MFM
authors.lastname: Gerli
authors.affiliation: Hematology Clinical Unit, Division of Regenerative Medicine, Gene Therapy and Stem Cells, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Marktel
authors.affiliation: Hematology Clinical Unit, Division of Regenerative Medicine, Gene Therapy and Stem Cells, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Napolitano
authors.affiliation: Hematology Clinical Unit, Division of Regenerative Medicine, Gene Therapy and Stem Cells, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cicalese
authors.affiliation: Hematology Clinical Unit, Division of Regenerative Medicine, Gene Therapy and Stem Cells, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.affiliation: Regenerative Orthopedic Department, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Peretti
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, UK; Hematology Clinical Unit, Division of Regenerative Medicine, Gene Therapy and Stem Cells, San Raffaele Scientific Institute, Milan, Italy; Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.affiliation: Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy. Electronic address: bonini.chiara@hsr.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonini
mesh_terms: D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D007371:Interferon-gamma
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