Stem Cell-Based Therapies Improved for Type 1 Diabetes

Type 1 diabetes (T1D) is the most common chronic autoimmune disease in young patients and is characterized by the loss of pancreatic β cells; as a result, the body becomes insulin deficient and hyperglycemic. Stem cell transplantation is a promising approach for the treatment of T1D. However, many unsolved issues need to be addressed before stem cell therapy will be clinically feasible for diabetic patients.

In recent years, researchers have made great progress in generating large numbers of stem cell-derived beta cells (sBCs) in the lab, but current methods to make mature, functioning sBCs and to remove any remaining residual stem cells which may cause tumors in patients are costly and labor-intense, and therefore difficult to implement in large scale. Now, researchers from the University of Florida found that dividing and potentially tumorigenic non-BCs can be eliminated from sBC cultures by a brief treatment with a chemotherapeutic drug.

Their new method is reported in Stem Cell Reports in an article titled, “Enrichment of stem cell-derived pancreatic beta-like cells and controlled graft size through pharmacological removal of proliferating cells.”

“Transplantation of limited human cadaveric islets into type 1 diabetic patients results in ∼35 months of insulin independence,” wrote the researchers. “Direct differentiation of stem cell-derived insulin-producing beta-like cells (sBCs) that can reverse diabetes in animal models effectively removes this shortage constraint, but uncontrolled graft growth remains a concern. Current protocols do not generate pure sBCs, but consist of only 20–50% insulin-expressing cells with additional cell types present, some of which are proliferative. Here, we show the selective ablation of proliferative cells marked by SOX9 by simple pharmacological treatment in vitro.”

The researchers reported that their new method not only prevented graft overgrowth and tumor formation after transplantation into diabetic mice but also enhanced the maturation and functionality of sBCs. The method may reduce the time and cost involved in producing safe and efficient sBC transplants, and eventually contribute to enhancing access to this type of treatment for more patients with T1D.

“While our work focused on the use of the chemotherapy drug Bleo, we anticipate that our work represents a proof of principle, and that other anti-proliferative drugs could be similarly employed to enrich for sBCs while depleting proliferating cells. Taken together, we provide convenient and effective means to deplete proliferative progenitors and simultaneously enrich for sBCs in differentiating cultures. As such, our findings carry important implications for current efforts focused on the use of sBCs for basic and translational research efforts.”

“Overall, our study provides a convenient and effective approach to enrich for sBCs while minimizing the presence of unwanted proliferative cells and thus has important implications for current cell therapy approaches,” concluded the researchers.

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