Improved approach to stem cell therapy for diabetes

A refined method has been developed to generate more mature, functional stem-cell-derived pancreatic islets that restore and maintain glucose control in diabetic mice over several months.

Type 1 diabetes is an autoimmune condition caused by destruction of pancreatic beta cells that produce insulin – a hormone that regulates blood glucose levels. Replacement approaches using donor or stem-cell-derived islets are being evaluated in clinical trials for type 1 diabetes, although most require immunosuppression or immune-protective devices. Previous methods for engineering these lab-grown islets have produced mixed cell populations with limited maturity and function. Now, researchers in Sweden have developed an improved strategy that consistently generates purer, more functional pancreatic islet-like clusters from eight human pluripotent stem cell lines.

'We have developed a method that reliably produces high-quality insulin-producing cells,' said Professor Per-Olof Berggren of the Karolinska Institutet in Stockholm, corresponding author of the study published in Stem Cell Reports. 'This opens up opportunities for future patient-specific cell therapies, which could reduce immune rejection.'

The authors modified existing protocols for creating stem-cell-derived islets and introduced two key improvements. First, they shortened the duration of an intermediate developmental stage, increasing the formation of precursor cells that later develop into hormone-producing pancreatic cells. Second, they implemented a spontaneous three-dimensional aggregation step to remove unwanted or rapidly dividing cells.

The optimised protocol was then tested across four induced pluripotent stem (iPS) cell and four embryonic stem cell lines, generating islet-like clusters with strong glucose-responsive metabolic function and structural features resembling human pancreatic islets.

The resulting stem-cell-derived islets were transplanted into mice with type 1 diabetes induced by streptozotocin, a chemical that selectively destroys insulin-producing beta cells. The anterior chamber of the eye was used to enable long-term monitoring of graft development and function. Over six months, no abnormal graft growth or cyst formation was observed.

'This is a technique we use to monitor the cells over time in a minimally invasive way,' explained Professor Berggren. 'We observed that the cells gradually matured after transplantation, retaining their ability to regulate blood sugar for several months, which demonstrates their potential for future treatments.'

Despite these promising results, the authors noted several limitations. The mechanism underlying enhanced precursor cell formation following shortening of the intermediate stage remains unclear. In addition, although standard functional tests were performed, further analyses are needed to confirm full functional maturity of the engineered islets. Safety and long-term stability of the graft beyond six months also remain unknown.

Transplantation of autologous iPS cell-derived islets has shown success in clinical studies (see BioNews 1259, 1295 and 1301); however, it remains unclear whether immunosuppression can be fully avoided. The authors suggest that their refined protocol represents a step towards autologous stem-cell-based therapies for type 1 diabetes by producing more uniform, mature pancreatic islets that may reduce immune rejection.

Professor Fredrik Lanner, senior author and researcher at the Karolinska Institutet, said: 'This could solve several of the problems that have previously hindered the development of stem cell-based treatments for type 1 diabetes.'