First Patient-Derived Stem Cell Transplant a Success in T1D

A new approach to using stem cell–derived pancreatic islets has allowed a patient with type 1 diabetes (T1D) to come off insulin for 1 year.

The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).

Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.

“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew and Hongkui Deng, both of Peking University Health Science Center, Beijing, China, told Medscape Medical News in an email. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.

The findings were published in Cell.

What’s New With This Approach?

The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Liew and Deng explained.

Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a non-transgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors…Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Liew and Deng explained.

A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site, they said.

Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post-transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”

Immunosuppression Remains a Challenge

Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and co-director of the Diabetes Center of Excellence at the UMass Chan Medical School, Worcester, Massachusetts, told Medscape Medical News, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but…that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”

Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”

Indeed, Liew and Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”

The team has now performed the same procedure in two more patients and will report their data “in due course.”

Liew had no disclosures. Deng is a scientific advisor at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Harlan is chief scientific officer and co-founder of Stability Health. He had no other disclosures.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape Medical News, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X: @MiriamETucker.