Treatment with Human Placental Lactogen (hPL-A) Improves Glucose Homeostasis One Year after Pancreatic Islets Transplantation in Mice Anterior Eye Chamber

Type 1 diabetes (T1D) is a chronic disease characterized by destruction of insulin producing beta cells in the pancreas. In addition to conventional insulin treatment, islets transplantation represents an alternative and promising therapeutic approach to treat patients with T1D. Increasing evidences suggest that human placental lactogen (hPL), a polypeptide placental hormone, is able to promote islets survival and proliferation in vitro, however it is unknown its implication in vivo models. Therefore, in the present study, we used hPL isoform A (hPL-A) to evaluate the role of this hormone in murine engrafted islets. T1D was induced in C57BL6/J male mice by a single intraperitoneal high dose (180 mg/kg) of streptozotocin (STZ). Collagenase p and a Histopaque 1110 gradient solution were used to isolate pancreatic islets. The anterior chamber of the eye was used to inject isolated islets. The engraftment was evaluated by confocal microscopy and immunohistochemical staining on section of the right and left eye. Glucose tolerance test (GTT) was used to assess glucose tolerance in mice. First, we evaluated the engraftment of freshly isolated pancreatic islets. Iris dissections showed a positive staining for insulin and glucagon. Second, since 2 months after transplantation, STZ-treated mice injected with islets stimulated with hPL-A, showed an improvement in fed glycaemia compared to STZ-treated mice transplanted with islets alone, and non-transplanted STZ-treated mice, for a follow-up of 1 year. Furthermore, mice treated with hPL-A, showed GTT with a similar pattern to untreated control mice; islets vascularization and angiogenesis was showed using CD31. Taken together, present results provide evidence that hPL-A could have a long-term effect on islet graft function and survival through enhancing glucose homeostasis.