Small Islets Transplantation Superiority to Large Ones: Implications from Islet Microcirculation and Revascularization

Abstract

Pancreatic islet transplantation is a promising therapy to regain glycemic control in diabetic patients. The selection of ideal grafts is the basis to guarantee short-term effectivity and longevity of the transplanted islets. Contradictory to the traditional notion, recent findings implied the superiority of small islets for better transplantation outcomes rather than the large and intact ones. However, the mechanisms remain to be elucidated. Recent evidences emphasized the major impact of microcirculation on islet β-cell mass and function. And potentials in islet graft revascularization are crucial for their survival and preserved function in the recipient. In this study, we verified the distinct histological phenotype and functionality of small islets versus large ones both in vitro and in vivo. With efforts to exploring the differences in microcirculation and revascularization of islet grafts, we further evaluated local expressions of angiotensin and vascular endothelial growth factor A (VEGF-A) at different levels. Our findings reveal that, apart from the higher density of insulin-producing β-cells, small islets express less angiotensin and more angiotrophic VEGF-A. We therefore hypothesized a logical explanation of the small islet superiority for transplantation outcome from the aspects of facilitated microcirculation and revascularization intrinsically in small islets.

Integrated whole liver histologic analysis of the allogeneic islet distribution and characteristics in a nonhuman primate model

“…S5a). The results, which showed a significantly larger distribution of small islets in the recipient liver with good prognosis after transplantation, are consistent with previous reports that small islets contributed to the transplantation outcome and show that this phenomenon is similar in cynomolgus monkeys 36,40 .…”

“…Similar to the correlation between the islet size and the results of transplantation, in many studies, the ratio of insulin-expressing beta cell content of islets was higher in smaller islets 36,[41][42][43] . The results from the present study confirmed this finding.…”

“…For many years, researchers have been interested in the relationship between islet size and transplantation outcomes 30,[35][36][37][38][39][40] . Small islets have a higher expression of factors involved in angiogenesis than large islets and may have a positive effect on transplant outcome due to reduced embolism based on the results of islets transplanted in small rodents 30,36 . Islets experience a hypoxic environment immediately after isolation from the pancreas and a hypoxic state due to delayed vascularization caused by a lack of oxygen supply by the thrombosis on the surface after being transplanted into the liver 37 .…”

A new scaffold containing small intestinal submucosa and mesenchymal stem cells improves pancreatic islet function and survival in vitro and in vivo

“…CD31 is a marker of the vascular endothelium (31). To investigate whether the SIS-MSC scaffold improves the microcirculation of islets, we performed an immunofluorescence analysis for CD31.…”

Engineering islet for improved performance by optimized reaggregation in alginate gel beads

“…Recent studies have found evidence that small islets have higher survival rates and superior function as compared with large islets, because small islets are able to effectively receive oxygen and nutrients through diffusion, even after they are deprived of their native vascular network . The transport of insulin also greatly relies on diffusion, and large islets are inferior due to central necrosis, whereas small islet cell clusters can successfully minimize diffusion barriers and maintain viability and function .…”