Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor. (10th June 2019)

• Record Type: Journal Article
• Authors: Mittal, Sharad K.; Foulsham, William; Shukla, Sachin; Elbasiony, Elsayed; Omoto, Masahiro; Chauhan, Sunil K.
• Is Part Of: Stem cells translational medicine. Volume 8:Number 10(2019)
• Page Start: 1030
• Page End: 1040
• Publication Date: 2019-06-10
• Subjects: Cornea -- Transplantation -- Mesenchymal stromal cells -- Hepatocyte growth factor; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.19-0004
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: Mesenchymal stromal cells (MSCs) are multipotent stem cells that participate in tissue repair and possess considerable immunomodulatory potential. MSCs have been shown to promote allograft survival, yet the mechanisms behind this phenomenon have not been fully defined. Here, we investigate the capacity of MSCs to suppress the allogeneic immune response by secreting the pleiotropic molecule hepatocyte growth factor (HGF). Using an in vivo mouse model of corneal transplantation, we report that MSCs promote graft survival in an HGF-dependent manner. Moreover, our data indicate that topically administered recombinant HGF (a) suppresses antigen-presenting cell maturation in draining lymphoid tissue, (b) limits T-helper type-1 cell generation, (c) decreases inflammatory cell infiltration into grafted tissue, and (d) is itself sufficient to promote transplant survival. These findings have potential translational implications for the development of HGF-based therapeutics. Stem Cells Translational Medicine 2019;8:1030–1040 : Abstract : Mesenchymal stromal cell-derived hepatocyte growth factor decreases antigen-presenting cell maturation, reduces T helper type 1 effector cell generation, limits inflammatory cell infiltration into grafted tissue and promotes corneal transplant survival.