Method improves safety of type 1 diabetes cell therapy aimed at eliminating need for insulin.

Close Cell therapy holds great promise as a treatment for type 1 diabetes, as it could eliminate the need for insulin injections.

In individuals with type 1 diabetes, insulin-producing beta cells are killed by the immune system. Cell therapy involves restoring these lost cells by using stem cells to make pancreatic cells in the lab, then injecting them into the pancreas.

“While cell therapies have the potential to revolutionize diabetes treatment, there are serious roadblocks to tackle before it can be widely used in the clinic,” says Dr. M. Cristina Nostro.

The barriers to cell therapy include the threat of the outgrowth of unwanted, non-pancreatic cells after transplantation. In experimental models, transplanting lab-produced pancreatic cells can lead to an increased risk of a type of outgrowth known as a teratoma. Dr. Nostro's laboratory recently published findings in the journal Stem Cell Reports that address this issue and improve the safety of potential cell therapies.

“We found a robust way to eliminate the chance of teratoma formation by purifying lab-produced pancreatic cells.” says Dr. Yasaman Aghazadeh, co-first author of the study and post-doctoral fellow at the McEwen Stem Cell Institute and the Toronto General Hospital Research Institute. Also read

The key to the research team’s approach is the use of a cell surface marker called glycoprotein 2 (GP2) to filter the cells before transplanting them. “While researchers have known that GP2 can be used to increase the purity of stem cell-derived pancreatic cells, it was unclear whether this approach improved the safety of cell therapy without jeopardizing therapeutic efficacy—until this study,” adds Dr. Aghazadeh.

To prepare pancreatic cells for experimental cell therapy studies, laboratories start with human pluripotent stem cells. These cells are coaxed to become pancreatic progenitors—immature pancreatic cells that can then develop and give rise to all of the cells found in the pancreas—including the insulin-producing beta cells.

“We further refined this process by adding a step in which we selected pancreatic precursor cells that had GP2 on their surface. We found that this step removes impurities—unwanted, off-target cells—and that this was sufficient for eliminating the risk of teratomas after transplantation,” says Farida Sarangi, co-first author and Research Associate in the laboratory of Dr. Nostro.

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