Umbilical cord-derived mesenchymal stem cells promote myeloid-derived suppressor cell enrichment by secreting CXCL1 to prevent graft-versus-host disease after hematopoietic stem cell transplantation

Cytotherapy. 2021 Nov;23(11):996-1006. doi: 10.1016/j.jcyt.2021.07.009. Epub 2021 Aug 29.

Abstract

Background aims: Human mesenchymal stem cells (MSCs) from various tissues have emerged as attractive candidates for the prevention and treatment of graft-versus-host disease (GVHD). However, the molecular machinery that defines and channels the behavior of these cells remains poorly understood.

Methods: In this study, the authors compared the efficacy of four tissue-derived MSC types in controlling GVHD in a murine model and investigated their immunomodulatory effects.

Results: Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) effectively decreased the incidence and severity of GVHD, which was mediated by the enrichment of myeloid-derived suppressor cells in GVHD target tissues. RNA sequencing results showed that hUCMSCs highly expressed CXCL1.

Conclusions: These results suggest a novel prophylactic application of hUCMSCs for controlling GVHD after allogeneic hematopoietic stem cell transplantation.

Keywords: cell therapy; chemokine; hematopoietic stem cell transplantation; immunosuppression; mesenchymal stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CXCL1
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells*
  • Mice
  • Myeloid-Derived Suppressor Cells*
  • Umbilical Cord

Substances

  • CXCL1 protein, human
  • Chemokine CXCL1