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

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 capac...

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Autores principales: Mittal, Sharad K., Foulsham, William, Shukla, Sachin, Elbasiony, Elsayed, Omoto, Masahiro, Chauhan, Sunil K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766689/
https://www.ncbi.nlm.nih.gov/pubmed/31179638
http://dx.doi.org/10.1002/sctm.19-0004
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author Mittal, Sharad K.
Foulsham, William
Shukla, Sachin
Elbasiony, Elsayed
Omoto, Masahiro
Chauhan, Sunil K.
author_facet Mittal, Sharad K.
Foulsham, William
Shukla, Sachin
Elbasiony, Elsayed
Omoto, Masahiro
Chauhan, Sunil K.
author_sort Mittal, Sharad K.
collection PubMed
description 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
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spelling pubmed-67666892019-10-01 Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor Mittal, Sharad K. Foulsham, William Shukla, Sachin Elbasiony, Elsayed Omoto, Masahiro Chauhan, Sunil K. Stem Cells Transl Med Cell‐Based Drug Development, Screening, and Toxicology 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 John Wiley & Sons, Inc. 2019-06-10 /pmc/articles/PMC6766689/ /pubmed/31179638 http://dx.doi.org/10.1002/sctm.19-0004 Text en © 2019 The Authors. stem cells translational medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Cell‐Based Drug Development, Screening, and Toxicology
Mittal, Sharad K.
Foulsham, William
Shukla, Sachin
Elbasiony, Elsayed
Omoto, Masahiro
Chauhan, Sunil K.
Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor
title Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor
title_full Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor
title_fullStr Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor
title_full_unstemmed Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor
title_short Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor
title_sort mesenchymal stromal cells modulate corneal alloimmunity via secretion of hepatocyte growth factor
topic Cell‐Based Drug Development, Screening, and Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766689/
https://www.ncbi.nlm.nih.gov/pubmed/31179638
http://dx.doi.org/10.1002/sctm.19-0004
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