Mesenchymal stem cells induced regulatory dendritic cells from hemopoietic progenitor cells through Notch pathway and TGF-β synergistically

Abstract

Mesenchymal stem cells (MSCs) are one of the attractive candidates in regenerative medicine of many clinical applications because of their low immunogenicity and immunomodulatory property. Our previous studies provided that mouse bone marrow-derived Sca-1⁺MSCs could drive the differentiation of regulatory DC (regDCs) (Scal-1⁺ BM-MSC-driven DC [sBM-DCs]) from hemopoietic progenitor cells (HPCs) and the Notch pathway played a critical role in maintaining the immunomodulatory property. However, the detailed mechanisms of their immunoregulatory capacity are not fully defined. In the present study, we show that BM-MSCs expressed high levels of Jagged 1 while sBM-DCs expressed high levels of Notch1. Jagged1 expressed on the surface of BM-MSCs initiated Notch signaling to maintain the immunomodulatory property of the sBM-DCs. The level of TGF-β is high in MSCs, either alone or coculture with HPCs medium. TGF-β plays a vital role in the proliferation and differentiation of sBM-DCs and inhibition of TGF-β reduce the number and increase the percentage of CD34, CD117, CD135 of generation cells. Thus, MSCs induced the regDCs from HPCs via the Notch signaling pathway and TGF-β synergistically. This study further broadens our understanding of the immunomodulatory mechanism and the potential therapeutic efficacy of MSCs.

Keywords: Mesenchymal stem cells; Notch signaling pathway; Regulatory dendritic cells; TGF-β.