A Comparative Study of Mesenchymal Stem Cell Derived From Human Embryonic Stem Cell-derived Mesenchymal Stem Cells Through a Trophoblast-like Stage and Bone Marrow-derived Mesenchymal Stem Cells in Treating Acute Xenogeneic Graft-versus-host Disease

BACKGROUND: Despite being promising candidates for treating acute graft-versus-host disease (aGvHD), the efficacy and underlying mechanisms of mesenchymal stem cells (MSCs) may vary based on their sources. METHODS: T-MSCs, derived from trophoblast cells, and BM-MSCs, derived from bone marrow cells, were investigated for their efficacy in alleviating aGvHD in humanized NOD.Cg-Prkdcscid Il2rgtm1vst/Vst (NPG) mice. Clinical scoring and pathological damage were evaluated. Flow cytometry and cytometric bead array were used to assess T-cell proliferation and related cytokine release. Mechanisms involved in MSC-related efficacy were probed using different inhibitors and blocking antibodies. RESULTS: An acute, single dose of T-MSCs (3 × 105 cells/mouse) or BM-MSCs (3 × 105 cells/mouse) significantly ameliorated aGvHD severity, whereas delayed, multiple doses of either MSC type did not. At the cellular level, both T-MSCs and BM-MSCs inhibited the proliferation of CD4+ and CD8+ T cells and the upregulation of related cytokines, possibly involving prostaglandin E2 but not indoleamine 2,3-dioxygenase 1, transforming growth factor-β, or the programmed death-ligand 1 or Fas signaling. Additionally, the CD3+CD25high+Foxp3+ T cells were increased by both MSC types. CONCLUSIONS: Both T-MSCs and BM-MSCs can prevent CD4+ and CD8+ T-cell proliferation, possibly by facilitating prostaglandin E2 release and promoting the proliferation of CD3+CD25high+Foxp3+ T cells, thereby alleviating the development of aGvHD. T-MSCs and BM-MSCs may serve as promising candidates for treating aGvHD in the clinical setting.