03 December 2021

Stem cells for diabetics

Stem cell implant did not help diabetics to give up insulin

Anastasia Kuznetsova-Fantoni, N+1

Canadian scientists implanted pancreatic cells grown from stem cells in 26 patients with type I diabetes. Interim results of clinical trials were published in Cell Stem Cell (Ramzy et al., Implanted pluripotent stem-cell-derived pancreatic endoderm cells secret glucose-responsive C-peptide in patients with type 1 diabetes). It was not possible to achieve a significant improvement in the condition of patients, but the researchers proved that the cells take root and produce insulin. In the future, scientists will have to think about how to improve the methodology and reduce the need for insulin for patients.

In diabetes mellitus of the first type, the body lacks insulin, because the beta cells of the pancreas that produce this hormone are destroyed. Doctors tried to replenish the dead cells and plant a new pancreas for the patient 60 years ago: the first donor organ was transplanted in the 1960s, and in the 1970s - separate islands of the pancreas. However, it was and remains difficult to find donor material, so scientists continued to look for a replacement.

Several research groups cultured stem cells for this purpose, in order to then turn them into pancreatic cells and plant them in diabetic patients. In the 2000s, Viacyte developed a protocol for growing embryonic stem cells, which are obtained from the internal cell mass of blastocysts at an early stage of embryo development. In parallel, such studies were conducted by Vertex — it used both embryonic stem cells and somatic ones.

After 15 years, the technique reached clinical trials. Vertex was the first to report on the preliminary results, although so far only about one of the patients. A man who was injected with pancreatic cells, three months later was able to reduce the daily dose of insulin by 91 percent.

Following their colleagues, the interim results of clinical trials were published by Viacyte. The researchers followed 26 patients for a year who were implanted with pancreatic cells grown from endoderm cells. Doctors led by Timothy J. Kieffer from the University of British Columbia have now provided information on only 15 patients. The implants were implanted under their skin and were accompanied by immunosuppressive therapy to avoid an attack on stem cells from the body.

All participants had increased (p = 0.026) levels of C-peptide, which is formed when proinsulin is cleaved by peptidases, 26 weeks after the procedure. This proves that the insulin levels in the blood of patients have increased. Despite this, the patients did not produce enough insulin after eating, so there were no significant improvements in their condition.

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The patients generally tolerated the treatment well, but two participants in clinical trials withdrew from them ahead of schedule due to the side effects of immunosuppressants - one had a liver abscess, and the other had a parvovirus infection. Scientists will have to think about how to help patients do without immunosuppressants. Perhaps the cells will have to be enclosed in a capsule and fenced off from the immune system. In the future, scientists will also have to adjust the number of stem cells in the implant in such a way as to achieve clinical improvements. But even in the absence of high-profile results, the work is of great importance. Researchers have proven that the technology is quite applicable in humans, because stem cells survive at least up to 59 weeks after implantation and all this time continue to secrete insulin.

A possible solution to the problem of rejection of transplanted cells was proposed by American scientists. To deliver pancreatic cells into the body, they used a shell of porous nanofibers that protects cells from the immune system.

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