Human iPSC-derived mesoangioblasts, like their tissue-derived counterparts, suppress T cell proliferation through IDO- and PGE-2-dependent pathways.
Human mesoangioblasts are currently in a phase I/II clinical trial for the treatment of patients with Duchenne muscular dystrophy. However, limitations associated with the finite life span of these cells combined with the significant numbers of mesoangioblasts required to treat all of the skeletal muscles in these patients restricts their therapeutic potential. Induced pluripotent stem cell (iPSC)-derived mesoangioblasts may provide the solution to this problem. Although, the idea of using iPSC-derived cell therapies has been proposed for quite some time, our understanding of how the immune system interacts with these cells is inadequate. Herein, we show that iPSC-derived mesoangioblasts (HIDEMs) from healthy donors and, importantly, limb-girdle muscular dystrophy 2D patients exert immunosuppressive effects on T cell proliferation.  Interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α) play crucial roles in the initial activation of HIDEMs and importantly indoleamine 2,3 dioxygenase (IDO) and prostaglandin E2 (PGE-2) were identified as key mechanisms involved in HIDEM suppression of T cell proliferation. Together with recent studies confirming the myogenic function and regenerative potential of these cells, we suggest that HIDEMs could provide an unlimited alternative source for mesoangioblast-based therapies.
Transplantation Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Ou
O
Li
Transplantation Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.|Cellular Immunology Group, Institute of Immunology, National University of Ireland Maynooth, Co. Kildare, Ireland.
Karen
K
English
Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Rossana
R
Tonlorenzi
Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.|Department of Cell and Developmental Biology and Centre for Stem Cells and Regenerative Medicine, University College London, London, UK.
Giulio
G
Cossu
Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.|Department of Cell and Developmental Biology and Centre for Stem Cells and Regenerative Medicine, University College London, London, UK.
Francesco
F
Saverio Tedesco
Transplantation Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Kathryn J
KJ
Wood