Transplantation of Encapsulated Embryonic Progenitor-Derived Insulin-Producing Cells Reverses Hyperglycemia in Immune-Competent Diabetic Animals.

Severe shortage of cadaveric pancreata has limited the effective therapy of type 1 diabetes by transplantation of isolated human pancreatic islets. Consequently, alternative approaches are intensively explored to generate surrogate beta-cells. We were able to differentiate mouse early embryo-derived progenitor cells into insulin-producing cells (referred to as MEPI-1 cells) which synthesize high levels of insulin, secrete insulin and C-peptide in response to elevated glucose, and can be propagated extensively in vitro. Transplantation of MEPI-1 cells under kidney capsules or subcutaneously in the axilla in streptozotocin (STZ)-induced type 1 diabetic immune-deficient SCID mice corrected hyperglycemia. However, transplantation of these cells in STZ-induced immune-competent diabetic mice only transiently corrected hyperglycemia for a few days. Severe inflammation at the transplantation site suggested acute immune rejection of MEPI-1 cells and consequently the failure to sustain reversal of hyperglycemia in immune competent mice. To circumvent this problem, MEPI-1 cells were micro-encapsulated in barium alginate (capsule size of 400-600 µm) using an electrostatic encapsulator. After overnight culture, the encapsulated cells (2.5-10 x 10[sup 6]) were transplanted intraperitoneally into immune-competent diabetic mice. Normoglycemic level was restored within 1-3 days, followed by development of hypoglycemia varying from 51-80 mg glucose/dL. Despite the hypoglycemia, these mice maintained a level of physical activity and weight gain comparable to that of nondiabetic controls. After more than 3 months, there was no relapse of hyperglycemia in these immune-competent diabetic mice implanted with encapsulated MEPI-1 cells. These results suggest that embryonic progenitor-derived insulin-producing cells may be used as the surrogate beta-cells to develop the transplantation therapy for type 1 diabetes. [ABSTRACT FROM AUTHOR]