Grant: Project Grant

Type 1 diabetes (T1D) is casued by an immune cells attack which destroy beta cells of the pancreas. The beta cells secrete insulin to lower blood glucose, therefore, their loss leads to high blood glucose, and requirement for insulin administration on a daily basis. Therefore, this treatment is burdensome for patients and their families. The only long-term therapy for T1D is receiving donor cells, yet the donor numbers are scarce. As an alternative source, stem cells are used which have the potential to develop all human tissues. The first protocols to generate pancreatic cells from stem cells was established in 2008, and the stem cell-pancreatic cells entered clinical trials in 2014. These trials failed because the cells were encapsulated in devices that prevented vascularization, therefore after transplant the cells could not connect to the host's vessels to acquire oxygen and nutrients. These devices were modified to incorporate pores, and a second trials was launched in 2017. One year results confirmed insulin secretion in 63% of recipients, but the levels were too low to normalize blood glucose. One reason was that the devices were partially vascularized, and cells located in the non-vascularized areas did not survive. The other reason was that the beta cells had low function, due to their immature (non-adult) nature. Previously, I isolated vessels from the fat which can be obtained with liposuction, and co-transplanted them with the stem cell pancreatic cells which demonstrated robust cell survival and significantly increased insulin secretion. Interestingly enough, when vessels were present the beta cells shifted towards an adult profile. Therefore, in this proposal, we aim to study the role of vessels in beta cell maturation, and function and develop vascularized islets with improved survival and function that can robustly normalize blood glucose in adult humans.