2. Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.
3. Stem Cell and Regeneration Theme, School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China.
4. The Chinese University Shenzhen Research Institute, Shenzhen, Guangdong Province, PR China.
Background: Transplanting bone marrow derived mesenchymal stem cells(MSCs) have positive effects in treating many disease conditions including diabetes. To investigate the effects of systemic administration of MSCs on blood glucose changes, we studied the changes of islet β and α cellsin STZ-induced diabetic rats following systemic MSCs administration.
Methods: MSCs were isolated from rat bone marrow, characterized, expanded in vitro and labeled with GFP by lentivirus transfection. 2x106 MSCs were injected into the rats via caudal vein at 10 days following STZ administration. The fasting glucose serum levels were measured following the treatment. Animals were terminated at day 21 and 35 following STZ injection. The insulin, Pdx1, glucagon and somatoatatin expressing cells in the pancreatic sections were quantified by immunofluorescence methods.
Results: We found that the blood glucose levels in the rats receiving MSCs were significantly reduced compared to the control group at day 21 following STZ treatment, and it reached to the similar high glucose level again at day 28. The injected MSCs were found in the pancreatic tissues, and the islets in the treatment group were partially restored in contrast to the control group. There were greater numbers of Pdx1+Insulin− cells in the MSCs treatment group, suggesting the ongoing regeneration of islet. The number of α cellswas significantly higher in the MSCs-treated group and untreated control group than that of normal group, which may associate with higher blood glucose level in later stage of MSCs administration. In addition, MSCs were co-cultured with the isolated rat islets and islet-like cells (INS1) in vitro and we found that the expression of Cdk4 was up-regulated in the islets when co-cultured with MSCs.
Conclusions: We concluded that transplanting allogenic MSCs may promote the regeneration of the injured islets, but the underlying mechanisms need further investigation.
Key words: Mesenchymal stem cells, islet regeneration, islet α and β cells, cdk4