Amniotic Membrane Extract Protects Islets From Serum-Deprivation Induced Impairments and Improves Islet Transplantation Outcome

Abstract

Islet culture prior to transplantation is a standard practice in many transplantation centers. Nevertheless, the abundant islet mass loss and function impairment during this serum-deprivation culture period restrain the success of islet transplantation. In the present study, we used a natural biomaterial derived product, amniotic membrane extract (AME), as medium supplementation of islet pretransplant cultivation to investigate its protective effect on islet survival and function and its underlying mechanisms, as well as the engraftment outcome of islets following AME treatment. Results showed that AME supplementation improved islet viability and function, and decreased islet apoptosis and islet loss during serum-deprived culture. This was associated with the increased phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway. Moreover, transplantation of serum-deprivation stressed islets that were pre-treated with AME into diabetic mice revealed better blood glucose control and improved islet graft survival. In conclusion, AME could improve islet survival and function in vivo and in vitro, and was at least partially through increasing phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway.

A Prevascularized Sinus Tract on the Liver Surface for Islet Transplantation

“…40 Our previous study also confirmed that the amniotic membrane extract contains multiple growth factors, including hepatocyte growth factor, epidermal growth factor, etc, which have protective effects on islet survival and function. 20 Therefore, compared with other prevascularization strategies, islet transplantation into PST on the liver surface may be independent of the additional administration of expensive growth factors 39,41,42 or other accessory cells (such as autologous adipose-derived stem cells or fibroblasts). 38,43 In this study, the flexibility of the amniotic membrane ensured a tight fit to the liver surface.…”

“…The selection criteria for participants and the written informed consent signing process were the same as described previously. 20…”

“…The selection criteria for participants and the written informed consent signing process were the same as described previously. 20 The DAM was prepared with some modifications based on the method described previously. 21,22 Briefly, the obtained fresh human amniotic membrane (Figure 1A) was repeatedly washed with 4 °C precooled phosphate buffer saline (PBS; Hyclone, Logan, UT) to remove clots, and then the human amniotic membrane was divided into small pieces and frozen in a solution consisting of a mixture of equal volumes of Dulbecco's Modified Eagle Medium (Hyclone) and glycerol (Solarbio, Beijing, China) at −80 °C.…”

The Influence of Microenvironment on Survival of Intraportal Transplanted Islets

“…Although the immunosuppressive regimen reported from Edmonton, Canada, has achieved unprecedented success in achieving insulin independence in islet transplantation ( 3 ), there are still some problems that affect the outcome of islet transplantation. Advancements in the acquisition of pancreatic islets, immunosuppression of islet recipients, and an increase in the number of transplanted islets are required ( 4 ). The average human pancreas has 300,000 to 1.5 million pancreatic islets, and only 60% of this islet cell mass is needed to maintain a normal glucose metabolism ( 5 ).…”