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Stem Cell-Derived Pancreatic Cells for Type 1 Diabetes

NEW YORK (Reuters Health) – An ongoing first-in-human trial suggests that pancreatic cells grown from stem cells can be safely implanted into patients with type 1 diabetes, and in some cases, begin producing insulin.

“I was surprised by how well the device implant and explant surgeries were tolerated by these patients, and to be able to measure human insulin in the blood in a third of (them),” Dr. A.M. James Shapiro of the University of Alberta told Reuters Health by email.

Dr. Shapiro led the team that developed the Edmonton Protocol, a process that allows transplantation of donated insulin-producing islet cells into the portal vein of people with type 1 diabetes.

In the new study, PEC-01 cells were implanted subcutaneously in macroencapsulation devices (VC-02; ViaCyte) into 17 patients (nine, male) ages 22-57, allowing for direct vascularization of the cells. All participants were negative for C-peptide at baseline.

The devices have ports in the membrane to allow the patient’s vasculature to grow into the lumen and directly vascularize the engrafted cells, thereby enhancing cell survival via improved oxygenation and metabolic exchange.

“These preliminary data from an ongoing first-in-human phase 1/2, open-label study provide proof-of-concept that pluripotent stem cell-derived pancreatic endoderm cells (PEC-01) engrafted in type 1 diabetes patients become islet cells releasing insulin in a physiologically regulated fashion,” Dr. Shapiro and colleagues write in Cell Reports.

Engraftment and insulin expression were observed in 63% of the VC-02 units explanted from participants at three months to a year post-implant. Three (35.3%) showed positive C-peptide at six months.

Most adverse events were related to the surgical implant or explant procedures (27.9%) or to side effects of immunosuppression (33.7%).

The authors conclude, “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.”

Dr. Shapiro said, “The next step is to transplant similar cells that have been gene edited to prevent rejection and improve survival. This is already happening with ViaCyte, and we plan to initiate first-in-human studies (now approved) in the next few weeks.”

The team will also continue its work on generating insulin-producing islet cells using cells from a patient’s own bloodstream. “A simple blood sample and some complex processing now allow us routinely to make human insulin-producing islets that are completely biocompatible with the same patient, so no anti rejection drugs will be needed,” he said. “There is a lot of work ahead to move this forward, but this is now possible and within reach.”

Dr. Andrew Stewart, Director, Diabetes Obesity and Metabolism Institute at the Icahn School of Medicine at Mount Sinai in New York City commented in an email to Reuters Health, “This is one of a series of recent reports showing that the path for stem cell-derived beta cells is moving forward, but still faces challenges and requires solving a number of unsolved problems.”

“It remains to be demonstrated that stem cell-derived beta cells can remain fully differentiated and functional – i.e., sensing glucose and producing normal amounts of insulin sufficient to maintain a normal blood glucose – for the long term, meaning years,” he noted. “This study shows that it is possible to some degree in some people for at least a matter of months, but more work is needed in learning how to keep transplanted beta cells happy, health and fully functional over the long term.”

“We still don’t have a well-tolerated and perfectly safe method to prevent rejection of transplanted human islets or stem cell-derived beta cells,” he added. “While many academic and commercial research labs are working on this, and progress is definitely being made, we are not completely done. More work is needed on developing safe, effective and well tolerated immunosuppressive drugs, and/or improved next-generation encapsulation devices.”

“My own group is focused on the development of drug treatments that can induce the residual beta cells – present in essentially all people with T1D and T2D – to regenerate, without the need for transplant (or) surgical interventions,” he noted. “We are closing in on the finish line on many fronts, but more work needs to be, and is being, done. The next several years will be exciting!”

The study did not receive commercial funding. However, seven coauthors are employees of ViaCyte and Dr. Shapiro and another coauthor are consultants to the company.

SOURCE: Cell Reports Medicine, online December 2, 2021.

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