Abstract

The trend of regenerative therapy for diabetes in human and veterinary practices has conceptually been proven according to the Edmonton protocol and animal models. Establishing an alternative insulin-producing cell (IPC) resource for further clinical application is a challenging task. This study investigated IPC generation from two practical canine mesenchymal stem cells (cMSCs), canine bone marrow-derived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs). The results illustrated that cBM-MSCs and cAD-MSCs contain distinct pancreatic differentiation potential and require the tailor-made induction protocols. The effective generation of cBM-MSC-derived IPCs needs the integration of genetic and microenvironment manipulation using a hanging-drop culture of PDX1-transfected cBM-MSCs under a three-step pancreatic induction protocol. However, this protocol is resource- and time-consuming. Another study on cAD-MSC-derived IPC generation found that IPC colonies could be obtained by a low attachment culture under the three-step induction protocol. Further, Notch signaling inhibition during pancreatic endoderm/progenitor induction yielded IPC colonies through the trend of glucose-responsive C-peptide secretion. Thus, this study showed that IPCs could be obtained from cBM-MSCs and cAD-MSCs through different induction techniques. Also, further signaling manipulation studies should be conducted to maximize the protocol’s efficiency.

Highlights

  • The trend of regenerative therapy for diabetes in human and veterinary practices has conceptually been proven according to the Edmonton protocol and animal models

  • The concept of stem cell (SC)-derived insulin-producing cell (IPC) transplantation for treating diabetes has been conceptually approved in animal models

  • For cBM-MSCs, we found that a 3D culture condition was required to form the IPC colony, which was considered as the native pancreatic islet m­ orphology[40,68,70,84]

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Summary

Introduction

The trend of regenerative therapy for diabetes in human and veterinary practices has conceptually been proven according to the Edmonton protocol and animal models. To earn the clinically applicable IPCs, a three-dimensional (3D) structure of IPCs floating or suspended in culture vessels would be required to ease the harvesting and encapsulating ­processes[15] To address this issue, the integrative induction protocols aiming for the pancreatic differentiation of canine bone marrow-derived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs) were established in this study. The integrative induction protocols aiming for the pancreatic differentiation of canine bone marrow-derived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs) were established in this study Both cells have been previously isolated, characterized, and studied for their potential application in some ­diseases[16,17,18,19,20]. The results will be the crucial platform supporting the IPC generation, which eventually benefits the establishment of clinical protocols for both veterinary and human applications

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