Adipose Tissue‐Derived Mesenchymal Stem Cells Have In Vivo Immunosuppressive Properties Applicable for the Control of the Graft‐Versus‐Host Disease

TLDR

Previous studies have shown that bone marrow‑derived mesenchymal stem cells can control graft‑versus‑host disease after allogeneic transplantation. The study aims to evaluate whether adipose tissue‑derived MSCs can control graft‑versus‑host disease in mice. The authors expanded human and mouse adipose‑derived MSCs, characterized their immunoregulatory properties, and tested their therapeutic effect in a mouse GVHD model. Expanded adipose‑derived MSCs displayed BM‑MSC–like immunophenotypes, suppressed T‑cell proliferation and cytokine release, and infusion of mouse Ad‑MSCs prevented lethal GVHD in a haploidentical transplant model, providing the first experimental evidence that Ad‑MSCs can control GVHD and suggesting clinical potential.

Abstract

Previous studies have shown the relevance of bone marrow-derived MSCs (BM-MSCs) in controlling graft-versus-host disease (GVHD) after allogeneic transplantation. Since adipose tissue-derived MSCs (Ad-MSCs) may constitute a good alternative to BM-MSCs, we have expanded MSCs derived from human adipose tissue (hAd-MSCs) and mouse adipose tissue (mAd-MSCs), investigated the immunoregulatory properties of these cells, and evaluated their capacity to control GVHD in mice. The phenotype and immunoregulatory properties of expanded hAd-MSCs were similar to those of human BM-MSCs. Moreover, hAd-MSCs inhibited the proliferation and cytokine secretion of human primary T cells in response to mitogens and allogeneic T cells. Similarly, ex vivo expanded mAd-MSCs had an equivalent immunophenotype and exerted immunoregulatory properties similar to those of hAd-MSCs. Moreover, the infusion of mAd-MSCs in mice transplanted with haploidentical hematopoietic grafts controlled the lethal GVHD that occurred in control recipient mice. These findings constitute the first experimental proof that Ad-MSCs can efficiently control the GVHD associated with allogeneic hematopoietic transplantation, opening new perspectives for the clinical use of Ad-MSCs.