'Milestone' in Stem-Cell-Based Islet Replacement for Type 1 Diabetes

By Reuters Staff

December 03, 2021

NEW YORK (Reuters Health) - Interim results from an ongoing multicenter clinical trial show that implanted pluripotent-stem-cell-derived endocrine progenitor cells can secrete insulin in patients with type 1 diabetes.

This is "an important milestone for the field of human pluripotent stem cell (PSC)-derived cell replacement therapies as it is one of the first to report cell survival and functionality one year after transplantation," write Dr. Eelco de Koning and Dr. Francoise Carlotti of Leiden University Medical Center, the Netherlands, in an editorial in Cell Stem Cell.

"A landmark has been set. The possibility of an unlimited supply of insulin-producing cells gives hope to people living with type 1 diabetes," they write.

The results were published this week in two companion papers in Cell Stem Cell and Cell Reports Medicine.

In the Cell Stem Cell paper, Dr. Timothy Kieffer of the University of British Columbia and colleagues report an interim analysis of 15 patients with type 1 diabetes who received subcutaneous implants of pancreatic endoderm cells (PEC) macroencapsulated in non-immunoprotective ("open") devices, which allowed for direct vascularization of the cells. All patients underwent an immunosuppressive regimen used commonly in donor islet transplant procedures.

The PEC implants, being developed by ViaCyte, were well tolerated with no teratoma formation or severe graft-related adverse events, and patients developed "meal-responsive insulin secretion post-implantation and retrieved grafts contained cells with a mature beta-cell phenotype," Dr. Kieffer and colleagues report.

During one year of follow-up, patients had 20% reduced insulin requirements and spent 13% more time in target blood-glucose range, the researchers say.

In the companion paper in Cell Reports Medicine, Dr. Howard Foyt of San Diego, California-based ViaCyte and colleagues report detectable engraftment and insulin expression in 63% of devices explanted from trial subjects at three to 12 months after implantation.

"Initial data suggest that pluripotent stem cells, which can be propagated to the desired biomass and differentiated into pancreatic islet-like tissue, may offer a scalable, renewable alternative to pancreatic islet transplants," write Dr. Foyt and colleagues.

"The present study demonstrates definitively for the first time to our knowledge, in a small number of human subjects with type 1 diabetes, that PSC-derived pancreatic progenitor cells have the capacity to survive, engraft, differentiate, and mature into human islet-like cells when implanted subcutaneously," Dr. Foyt added in a news release.

"Regarding safety, most (severe) adverse events were associated with the use of immunosuppressive agents, which is not unexpected and similar to allogeneic solid organ transplantation. It further emphasizes the life-long use of immunosuppressive agents as a major hurdle for wider implementation of allogeneic cell replacement therapies," Dr. de Koning and Dr. Carlotti note in their editorial.

They caution that many questions remain unanswered.

"The clinical road to wide implementation of stem cell-derived islet replacement therapy for type 1 diabetes is likely to be long and winding. Until that time, donor pancreas and islet transplantation will remain important therapeutic options for a small group of patients. But an era of clinical application of innovative stem-cell based islet replacement therapy for the treatment of diabetes has finally begun," the editorialists write.

This research was supported by funding from the Stem Cell Network, JDRF, Canadian Institutes of Health Research, ViaCyte, Inc., and California Institute for Regenerative Medicine. Several authors have financial relationships with ViaCyte Inc.

SOURCES: https://bit.ly/3dfGM5q and https://bit.ly/3DiJwd4 Cell Stem Cell and Cell Reports Medicine, online December 2, 2021.