Wharton's Jelly Mesenchymal Stromal Cells from Human Umbilical Cord: a Close-up on Immunomodulatory Molecules Featured In Situ and In Vitro

Stem Cell Rev Rep. 2019 Dec;15(6):900-918. doi: 10.1007/s12015-019-09907-1.

Abstract

Therapeutic options for end-stage organ failure are often limited to whole organ transplantation. The tolerance or rejection of the transplanted organ is driven by both early non-specific innate and specific adaptive responses. The use of mesenchymal stromal cells (MSCs) is considered a promising tool in regenerative medicine. Human umbilical cord (HUC) is an easily available source of MSCs, without relevant ethical issues. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs), showed consistent immunomodulatory features that may be useful to promote immune tolerance in the host after transplantation. Few data are available on the phenotype of WJ-MSCs in situ. We investigated the expression of immune-related molecules, such as HLAs, IDO, CD276/B7-H3, and others, both in situ (HUC) and in in vitro-cultured WJ-MSCs. Morphological and biochemical techniques were used to define the expression of such molecules. In addition, we focused on the possible role of CD276/B7-H3 on T cells proliferation inhibition. We assessed CD276/B7-H3 expression by WJ-MSCs both in situ and alongside cell culture. WJ-MSCs were able to suppress T cell proliferation in mixed lymphocyte reaction (MLR). Moreover, we describe for the first time a specific role for CD276/B7-H3, since the immunomodulatory ability of WJ-MSCs was abolished upon anti-CD276/B7-H3 antibody addition to the MLR. These results further detail the immune regulation properties and tolerance induction exerted by human WJ-MSCs, in particular pointing to CD276/B7-H3 as one of the main involved factors. These data further suggest WJ-MSCs as potent tools to modulate local immune response in "support-type" regenerative medicine approaches.

Keywords: B7-H3; CD276; Cell therapy; Human umbilical cord; Immunomodulation; Lymphocyte inhibition; Regenerative medicine; Stem cells; Wharton’s jelly mesenchymal stromal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7 Antigens / antagonists & inhibitors*
  • B7 Antigens / immunology
  • Cell Differentiation*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Humans
  • In Vitro Techniques
  • Lymphocyte Activation / immunology*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / immunology*
  • Umbilical Cord / cytology
  • Umbilical Cord / immunology*
  • Wharton Jelly / cytology
  • Wharton Jelly / immunology*

Substances

  • B7 Antigens
  • CD276 protein, human
  • Cytokines