Bioengineered regenerative therapy for diabetes mellitus: establishment of canine mesenchymal stem cell-derived insulin producing cells

Abstract

Trend of regenerative therapy for diabetes in human and veterinary practice has conceptually been proven according to Edmonton protocol and animal models. Establishing an alternative insulin-producing cell (IPC) resource is a challenge task for further clinical application. In this study, IPC generation from two practical canine mesenchymal stem cells (cMSCs), canine bone marrow-derived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs), was of interest. The results illustrated that cBM-MSCs and cAD-MSCs contained distinct pancreatic differentiation potential and required the tailor-made induction protocols. Generation of functional cBM-MSC-derived IPCs needed an integration of genetic and microenvironment manipulation using hanging-drop culture of PDX-1-transfected cBM-MSCs under three-step pancreatic induction protocol. However, this protocol was resource- and time-consumed. Another study on cAD-MSC-derived IPC generation found that IPC-like colonies could be obtained by low attachment culture under three-step induction protocol. Further Notch signaling inhibition during pancreatic endoderm/progenitor induction yielded IPC-like colonies with trend of glucose-responsive C-peptide secretion. Thus, this study showed that IPC-like cells could be obtained from cBM-MSCs and cAD-MSCs by different induction techniques, and further signaling manipulation study should be conducted to maximize the protocol efficiency.