Superior Migration Ability of Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) Toward Activated Lymphocytes in Comparison with Bone Marrow and Adipose-Derived MSCs

Mesenchymal stromal cells (MSCs) are obtained from several sources, including the bone marrow (BM), and adipose tissue (AD), and umbilical cord (UC). MSCs are activated upon the inflammation and / or tissue damage and migrate there to suppress the inflammation and repair tissues. Using these potencies, MSCs have been used clinically as various immunotherapies and regenerative medicines including the acute graft-versus-host disease (GVHD), cerebral palsy, COVID-19 related acute respiratory distress syndrome (ARDS). Severe acute GVHD is one of the major adverse events after allogeneic hematopoietic stem cell transplantation (HSCT). The mixed lymphocyte reaction (MLR) assay, in which the lymphocyte activation are induced by the co-culture of the allogeneic cells such as dendritic cells, mimic the acute GVHD. To find the suitable tissue as MSCs source for acute GVHD, we investigated the proliferation, immunosuppression, and migration potency of UC-MSCs in comparison with the BM and AD - derived MSCs. The migratory potency of MSCs were evaluated by transwell migration assay with the MSCs in upper chamber toward the lymphocytes activated in allogeneic MLR in lower chamber. Proliferation of UC-MSCs, BM-MSCs, and AD-MSCs was compared. UC-MSCs demonstrated the significant higher proliferation ability with higher proliferation speed compared with those of BM-MSCs and AD-MSCs. The mean ± SD proliferation limit was 43.2 ±7.4 PDL in UC-MSCs (n=4), 19.6 ±4.1 in BM-MSCs (n=3), and 30.9 ± 7.3 in AD-MSCs(n=3), respectively. UC, BM, and AD-MSCs equivalently suppressed the activated lymphocyte proliferation in allogenic MLR. UC-MSCs showed the relatively higher migration ability even without stimulation. MSCs showed significant higher migration potency toward mononuclear cells (MNCs) and MLR compared with those of BM- and AD-MSCs (n=3, P<0.05), while migration potency of three MSCs were comparable in the presence of fetal bovine serum. Chemokines in the supernatant of MLR co-cultured with UC-MSCs showed significant higher secretion of CCL2 (MCP-1) compared with those with BM-MSCs and AD-MSCs, although MNCs in MLR were not induced to secrete CCL2. IP-10 The migration of UC-MSCs toward MLR were attenuated by the inhibitor of PDGF, IGF-1, and MMP inhibitor in dose-dependent manner. Conclusively, superior and migration potency of UC-MSCs might give the benefit of allogeneic stimuli such as graft-versus-host disease and superior proliferation potency may give the medical economic benefit.

No relevant conflicts of interest to declare.