Microencapsulation of cellular aggregate composed of differentiated insulin and glucagon-producing cells from human mesenchymal stem cells derived from adipose tissue.

Abstract Background. In type I diabetes mellitus (T1DM) pancreatic β cells are destroyed. Treatment entails exogenous insulin administration and strict diet control, yet optimal glycemic control is hardly attainable. Islet transplant could be an alternative in patients with poor glycemic control, but inefficient islet purification and autoimmune response of patients still a challenge. Methods Human adipose-derived mesenchymal stem cells (hASC) obtained from lipoaspirated fat tissue from human donors were differentiated in vitro to insulin (Ins) and glucagon (Gcg) producing cells (IPC and GPC respectively). Then, we cocultured IPC and GPC cells in low adhesion conditions to form cellular aggregates, which were encapsulated in a sodium alginate polymer. Expression of pancreatic lineage markers and secretion of insulin or glucagon in vitro were analyzed. Results We demonstrated that multipotent hASC efficiently differentiate to IPC and GPC, which also express pancreatic markers, including insulin or glucagon hormones. In turn, we calculated the Feret diameter of cellular aggregates, finding mean diameters ~80 µm at 72h of incubation. IPC/GPC aggregates were then microencapsulated in sodium-alginate polymer microgels, which were found to be more stable in Ba 2+ stabilized microgels, with average diameters ~300 µm. Interestingly, Ba 2+ -microencapsulated aggregates respond to high external glucose with insulin secretion. Conclusions The IPC/GPC differentiation process from hASC followed by generate cellular aggregates in vitro, that once microencapsulated could represent a possible treatment to T1DM.