Immunogenicity of allogeneic mesenchymal stem cells transplanted via different routes in diabetic rats.

Due to their hypoimmunogenicity and unique immunosuppressive properties, mesenchymal stem cells (MSCs) are considered one of the most promising adult stem cell types for cell therapy. Although many studies have shown that MSCs exert therapeutic effects on several acute and subacute conditions, their long-term effects are not confirmed in chronic diseases. Immunogenicity is a major limitation for cell replacement therapy, and it is not well understood in vivo. We evaluated the immunogenicity of allogeneic MSCs in vivo by transplanting MSCs into normal and diabetic rats via the tail vein or pancreas and found that MSCs exhibited low immunogenicity in normal recipients and even exerted some immunosuppressive effects in diabetic rats during the initial phase. However, during the later stage in the pancreas group, MSCs expressed insulin and MHC II, eliciting a strong immune response in the pancreas. Simultaneously, the peripheral blood mononuclear cells in the recipients in the pancreas group were activated, and alloantibodies developed in vivo. Conversely, in the tail vein group, MSCs remained immunoprivileged and displayed immunosuppressive effects in vivo. These data indicate that different transplanting routes and microenvironments can lead to divergent immunogenicity of MSCs.

[Role of INGAP-pp in the differentiation of hUCMSCs into insulin producing cells].

OBJECTIVE: To find out a protocol for the efficient and directional differentiation from human umbilical cord mesenchymal stem cells (hUCMSCs) into insulin-producing cells (IPCs). METHODS: HUCMSCs were induced to differentiate into IPCs by an improved protocol based on a traditional protocol with addition of islet neogenesis-associated protein-pp (INGAP-pp), and the IPCs were identified by morphological observation, flow cytometry, real-time quantitative PCR, immunofluorescence and ELISA. RESULTS: Compared with the traditional protocol, the improved protocol resulted in the higher rate of C peptide positive cells (P<0.05) and the increased mRNA expressions of pancreas development related transcription factor PDX-1, Ngn3, NeuroD1, MafA, insulin, Glut-2 (P<0.05). Meanwhile, by the improved protocol the protein expressions of C peptide, PDX-1 and Nkx6.1 were positive, and insulin and C-peptide release were promoted (P<0.05) as demonstrated by glucose challenge test. CONCLUSION: INGAP-pp may facilitate the differentiation of hUCMSCs into IPCs. However, the IPCs are not as mature as normal human islet ß cells.