Immunogenicity of insulin-producing cells derived from human umbilical cord mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) have been considered as hypo-immunogenic and immunosuppressive. However, a thorough understanding of the immunological properties after MSC differentiation <i>in vitro</i> and <i>in vivo</i> has not been reached. We asked whether it would be immunogenic after differentiation or influenced by the immune microenvironment after transplantation. In different disease models, the immunological changes of MSCs after differentiation greatly varied, with contradicting results. In order to clarify this, we used a modified four-step induction method to induce human umbilical cord MSCs (hUCMSCs) to differentiate into insulin-producing cells (IPCs), and investigate the immunological changes after differentiation and immune reactions after transplantation into diabetic mice. We found that the induced IPCs are hypo-immunogenic, lacking HLA-DR, CD40 and CD80 expression. Of note, we observed immune cell infiltration to peritoneal cavity and left kidney capsule after local transplantation of induced IPCs. This indicated that hUCMSC-derived IPCs maintained hypo-immunogenic <i>in vitro</i>, but became immunogenic after transplanting to the host, possibly due to the changes of immune microenvironment and thereafter immunological enhancement and immune cell infiltration.