Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor

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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
Funding Information
  • Eye Bank Association of America
  • National Institutes of Health (P30EY003790, EY024602)
  • Eye Bank Association of America
  • National Institutes of Health (P30EY003790, EY024602)

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