Diabetes develops when the physique fails to handle its blood glucose ranges. One type of diabetes causes the physique to not reply to insulin in any respect. Known as Sort 1 diabetes, or T1D, this autoimmune illness occurs when the physique’s protection system errors its personal insulin-producing cells as international and kills them. On common, T1D can lead sufferers to lose a mean of 32 years of wholesome life.
Present therapy for T1D includes lifelong insulin injections. Whereas efficient, sufferers taking insulin threat creating low blood glucose ranges, which may trigger signs corresponding to shakiness, irritability, starvation, confusion and dizziness. Extreme circumstances may end up in seizures or unconsciousness. Actual-time blood glucose displays and injection gadgets may help keep away from low blood sugar ranges by controlling insulin launch, however they don’t work for some sufferers.
For these sufferers, a therapy referred to as islet transplantation may help higher management blood glucose by giving them each new insulin-producing cells in addition to cells that stop glucose ranges from falling too low. Nonetheless, it’s restricted by donor availability and the necessity to use immunosuppressive medication. Solely about 10% of T1D sufferers are eligible for islet transplants.
In my work as a diabetes researcher, my colleagues and I’ve discovered that making islets from stem cells may help overcome transplantation challenges.
Historical past of islet transplantation
Islet transplantation for Sort 1 diabetes was FDA permitted in 2023 after greater than a century of investigation.
Insulin-producing cells, additionally referred to as beta cells, are situated in areas of the pancreas referred to as islets of Langerhans. They’re current in clusters of cells that produce different hormones concerned in metabolism, corresponding to glucagon, which will increase blood glucose ranges; somatostatin, which inhibits insulin and glucagon; and ghrelin, which alerts starvation. Anatomist Paul Langerhans found islets in 1869 whereas finding out the microscopic anatomy of the pancreas, observing that these cell clusters stained distinctly from different cells.
The street to islet transplantation has confronted many hurdles since pathologist Gustave-Édouard Laguesse first speculated concerning the function islets play in hormone manufacturing within the late nineteenth century. In 1893, researchers tried to deal with a 13-year-old boy dying of diabetes with a sheep pancreas transplant. Whereas they noticed a slight enchancment in blood glucose ranges, the boy died three days after the process.
The islets of Langerhans, situated within the pancreas and coloured yellow right here, secrete hormones corresponding to insulin and glucagon.
Steve Gschmeissner/Science Photograph Library by way of Getty Photos
Curiosity in islet transplantation was renewed in 1972, when scientist Paul E. Lacy efficiently transplanted islets in a diabetic rat. After that, many analysis teams tried islet transplantation in individuals, with no or restricted success.
In 1999, transplant surgeon James Shapiro and his crew efficiently transplanted islets in seven sufferers in Edmonton, Canada, by transplanting a lot of islets from two to a few donors without delay and utilizing immunosuppressive medication. Via the Edmonton protocol, these sufferers have been capable of handle their diabetes with out insulin for a 12 months. By 2012, over 1,800 sufferers underwent islet transplants primarily based on this system, and about 90% survived via seven years of follow-up. The primary FDA-approved islet transplant remedy relies on the Edmonton protocol.
Stem cells as a supply of islets
Islet transplantation is now thought of a minor surgical procedure, the place islets are injected right into a vein within the liver utilizing a catheter. So simple as it might appear, there are lots of challenges related to the process, together with its excessive price and a restricted availability of donor islets. Transplantation additionally requires lifelong use of immunosuppressive medication that permit the international islets to dwell and performance within the physique. However using immunosuppressants additionally will increase the chance of different infections.
To beat these challenges, researchers are trying into utilizing stem cells to create a limiteless supply of islets.
There are two sorts of stem cells scientists are utilizing for islet transplants: embryonic stem cells, or ESCs, and induced pluripotent stem cells, or iPSCs. Each varieties can mature into islets within the lab.
Every has advantages and disadvantages.
There are moral considerations relating to ESCs, since they’re obtained from lifeless human embryos. Transplanting ESCs would nonetheless require immunosuppressive medication, limiting their use. Thus, researchers are working to both encapsulate or make mutations in ESC islets to guard them from the physique’s immune system.
Conversely, iPSCs are obtained from pores and skin, blood or fats cells of the affected person present process transplantation. Because the transplant includes the affected person’s personal cells, it bypasses the necessity for immunosuppressive medication. However the price of producing iPSC islets for every affected person is a significant barrier.
A protracted life with Sort 1 diabetes is feasible.
Stem cell islet challenges
Whereas iPSCs might theoretically keep away from the necessity for immunosuppressive medication, this technique nonetheless must be examined within the clinic.
T1D sufferers who’ve genetic mutations inflicting the illness presently can not use iPSC islets, for the reason that cells that may be taken to create stem cells can also carry the identical disease-causing mutation of their islet cells. Many obtainable gene-editing instruments might doubtlessly take away these mutations and generate useful iPSC islets.
Along with the problem of genetic tweaking, worth is a significant situation for islet transplantation. Transplanting islets constituted of stem cells is dearer than insulin remedy due to increased manufacturing prices. Efforts to scale up the method and make it more economical embody creating biobanks for iPSC matching. This might permit iPSC islets for use for a couple of affected person, lowering prices by avoiding the necessity to generate freshly modified islets for every affected person. Embryonic stem cell islets have an analogous benefit, as the identical batch of cells can be utilized for all sufferers.
There may be additionally a threat of tumors forming from these stem cell islets after transplantation. To this point, lab research on rodents and medical trials in individuals have not often proven any most cancers. This means the possibilities of these cells forming a tumor are low.
That being stated, many rounds of analysis and growth are required earlier than stem cell islets can be utilized within the clinic. It’s a laborious trek, however I imagine a number of extra optimizations may help researchers beat diabetes and save lives.
