I. Progress Towards a Stem Cell Based Therapy for Diabetes.

Abstract

Diabetes results from insufficient production of the hormone insulin from beta cells in pancreatic islets. Islet transplantation can replace the lost beta cells in patients but is limited by the scarcity of available donor organs. Our aim is to differentiate pluripotent stem cells into functional islets that can serve as an unlimited source for transplantation to treat diabetes. We have investigated the therapeutic potential of pancreatic endoderm cells derived from human embryonic stem cells. Several weeks following transplant into diabetic rodents, these cells mature and secrete sufficient human insulin, in a regulated manner, to reverse diabetes. In rats, we observed inconsistent survival of pancreatic endoderm cells implanted subcutaneously in macroencapsulation devices designed to be immunoprotective via use of a cell impermeable layer, but this was rectified by the addition of portals designed to enable direct capillary vascular permeation into the device interior. In contrast both device types supported cell survival, differentiation and function in mice, with more rapid C-peptide release and better glucose tolerance observed using the devices containing portals. Kidney capsule grafts often contained ductal cells and cysts, whereas cells implanted subcutaneously within macroencapsulation devices differentiated predominantly to endocrine cells. In collaboration with Aspect Biosystems, we are also exploring the feasibility of using 3D bioprinting as an approach to both contain implanted islet cells and protect them from immune attack. As part of a ViaCyte clinical trial (clinicaltrial.gov identifier: NCT03163511), we investigated the safety and efficacy of pancreatic endoderm cells implanted in nonimmunoprotective macroencapsulation devices for the treatment of patients with type 1 diabetes and hypoglycemic unawareness. Patients underwent subcutaneous implant of cell products combined with an immunosuppressive regimen. After implant, patients had increased fasting Cpeptide levels, increased glucose-responsive C-peptide levels, and developed mixed meal-stimulated C-peptide secretion. Patients had reduced insulin requirements, increased time in target blood glucose range, and improved hypoglycemic awareness. Explanted grafts contained cells with a mature beta cell phenotype that were immunoreactive for insulin, islet amyloid polypeptide, and MAFA. Collectively, these findings support future investigation into optimizing cell therapies for diabetes.

• Authors: Timothy J Kieffer
• Journal: Journal of stem cells & regenerative medicine (J Stem Cells Regen Med) Vol. 17 Issue 2 Pg. 61 ( 2021) ISSN: 0973-7154 [Print] India
• PMID: 35250203 (Publication Type: Journal Article)
• Copyright: Copyright © Journal of Stem Cells and Regenerative Medicine.