Insulin-Producing Cell Transplantation Platform for Veterinary Practice

Abstract

Diabetes mellitus (DM) remains a global concern in both human and veterinary medicine. Type I DM requires prolonged and consistent exogenous insulin administration to address hyperglycemia, which can increase the risk of diabetes complications such as retinopathy, nephropathy, neuropathy, and heart disorders. Cell-based therapies have been successful in human medicine using the Edmonton protocol. These therapies help maintain the production of endogenous insulin and stabilize blood glucose levels and may possibly be adapted to veterinary clinical practice. The limited number of cadaveric pancreas donors and the long-term use of immunosuppressive agents are the main obstacles for this protocol. Over the past decade, the development of potential therapies for DM has mainly focused on the generation of effective insulin-producing cells (IPCs) from various sources of stem cells that can be transplanted into the body. Another successful application of stem cells in type I DM therapies is transplanting generated IPCs. Encapsulation can be an alternative strategy to protect IPCs from rejection by the body due to their immunoisolation properties. This review summarizes current concepts of IPCs and encapsulation technology for veterinary clinical application and proposes a potential stem-cell-based platform for veterinary diabetic regenerative therapy.

Alginate/Pluronic F127-based encapsulation supports viability and functionality of human dental pulp stem cell-derived insulin-producing cells

“…Another challenge of cell-based therapy for translational study and clinical application is how to maintain the viability and functionality of the IPCs. Encapsulation can be applied to address this challenge due to the ability on rejection avoiding [ 18 , 19 ]. Alginate is a material that widely used in biomedical field, drug delivery and tissue engineering [ 20 ], since it provides advantages i.e.…”

Tailor-made generation of insulin-producing cells from canine mesenchymal stem cells derived from bone marrow and adipose tissue

“…Previous publications reported that small molecule induction could imitate the environment during pancreatic endocrine development 10,16,43,[51][52][53][54][55][56] . Generally, an in vitro pancreatic differentiation from SCs could be categorized into 6 differentiation stages: pluripotent/multipotent SCs, mesendoderm, definitive endoderm, pancreatic endoderm, pancreatic endocrine, and pancreatic beta-cells/IPCs 15,57 . In this study, activin A was used to mimic the effects of endogenous noggin for shortcutting the definitive endoderm establishing step as described in previous reports 32, [57][58][59][60][61][62] .…”

“…One of the potential transplantation platforms is cell or colony encapsulation which requires the 3D colony structure of the IPCs that can be harvested after an in vitro production. This encapsulation platform can support and immobilize IPC colonies with the immunoisolating property against host immunity 15 . By comparing the potential clinical application, it seemed that cBM-MSC-derived IPCs showed less potential due to the complicated and time/labor-consumed induction protocol.…”

“…These generated IPCs were formed as cell aggregates attached to culture surface that might cause some difficulties during cell harvesting and processing for transplantation. To earn the clinical applicable IPCs, three-dimensional (3D) structure of IPCs floating or suspending 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 marrowderived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs) were established in this study.…”

Tailored generation of insulin producing cells from canine mesenchymal stem cells derived from bone marrow and adipose tissue

“…These generated IPCs are formed as cell aggregates attached to the culture surface, which might cause some difficulties during cell harvesting and processing for transplantation. 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.…”