Subcutaneous transplantation of embryonic pancreas for correction of type 1 diabetes

Abstract

Islet transplantation is a promising therapeutic approach for type 1 diabetes. However, current success rates are low due to progressive graft failure in the long term and inability to monitor graft development in vivo. Other limitations include the necessity of initial invasive surgery and continued immunosuppressive therapy. We report an alternative transplantation strategy with the potential to overcome these problems. This technique involves transplantation of embryonic pancreatic tissue into recipients' subcutaneous space, eliminating the need for invasive surgery and associated risks. Current results in mouse models of type 1 diabetes show that embryonic pancreatic transplants in the subcutaneous space can normalize blood glucose homeostasis and achieve extensive endocrine differentiation and vascularization. Furthermore, modern imaging techniques such as two-photon excitation microscopy (TPEM) can be employed to monitor transplants through the intact skin in a completely noninvasive manner. Thus, this strategy is a convenient alternative to islet transplantation in diabetic mice and has the potential to be translated to human clinical applications with appropriate modifications.

Quantitative Measurement of Zinc Secretion from Pancreatic Islets with High Temporal Resolution Using Droplet-Based Microfluidics

“…It has been shown that donor islets transplanted into the livers of patients with type I diabetes can result in complete insulin independence within weeks 6. Recent studies have shown that subcutaneous islet transplants are capable of normalizing blood glucose homeostasis and achieving endocrine differentiation and vascularization 7. Hence islets are capable of what appears to be normal function in an environment of non-native tissue.…”

Passively Operated Microfluidic Device for Stimulation and Secretion Sampling of Single Pancreatic Islets

“…7 Islet transplantation is a promising treatment that has been shown to reverse the effects of islet loss in type 1 diabetes, yet further research is needed to enhance islet survival and to address the immune reaction of transplant recipients. 8,9 Most research to date has focused on the insulin-secreting β-cells within islets, which helps to ensure blood glucose homeostasis. However, recent work has highlighted the importance of paracrine communication among the multiple cell types within the islet, 10,11 indicating a need for more refined methods in studying the multicellular architecture of islets and its relation to function.…”

Therapeutic value of brown adipose tissue

“…The possibility of regulating blood glucose using a physiological combination of alternate hormones was first suggested in our early studies, where subcutaneous transplants of embryonic pancreatic tissue resulted in correction of chemically induced T1D with no accompanying increase in insulin 38 , 39 . Diabetic mice who received embryonic pancreatic transplants made a complete and permanent recovery with no detectable increase in the insulin response, exhibiting proliferation of WAT and increased plasma levels of adipokines instead.…”