Abstract
In this study we aim to boost the functional output of the intra-kidney islet transplantation for diabetic patients using a tissue engineered polymeric scaffold. This highly porous electrospun scaffold featured randomly distributed fibers composed of polycaprolactone (PCL) and poliglecaprone (PGC). It successfully sustained murine islets in vitro for up to 4 weeks without detected cytotoxicity. The in vivo study showed that the islet population proliferated by 89% within 12 weeks when they were delivered by the scaffold but only 18% if freely injected. Correspondingly, the islet population delivered by the scaffold unleashed a greater capability to produce insulin that in turn further drove down the blood glucose within 12 weeks after the surgery. Islets delivered by the scaffold most effectively prevented diabetic deterioration of kidney as evidenced by the lack of a kidney or glomerular enlargement and physiological levels of creatinine, urea nitrogen and albumin through week 12 after the surgery. Unlike traditional wisdom in diabetic research, the mechanistic study suggested that monocytes chemoattractant protein-1 (MCP-1) was responsible for the improved preservation of renal functions. This study revealed a therapeutic role of MCP-1 in rescuing kidneys in diabetic patients, which can be integrated into a tissue engineered scaffold to simultaneously preserved renal functions and islet transplantation efficacy. Also, this study affords a simple yet effective solution to improve the clinical output of islet transplantation.
Highlights
According to the American Diabetes Association, the diabetes inflicts 25.8 million patients in the U.S in 2011 and will dramatically increase the likelihood of other diseases, such as heart diseases, kidney failure, nervous system diseases, etc
We pioneered the employment of an electrospun composite scaffold of polycaprolactone (PCL) and poliglecaprone (PGC) as the delivery vehicle for syngeneic murine islet transplantation to improve the clinical performance of islet transplantation in diabetic patients
Starting from week 2, the islet population on the scaffold outgrew its peer on the tissue culture plate (TCP), suggesting that the electrospun scaffold provided a more favorable biochemical and biophysical environment for islets to adhere and grow, and that these scaffolding materials, either intact or degraded, possessed no cytotoxicity to islets
Summary
According to the American Diabetes Association, the diabetes inflicts 25.8 million patients in the U.S in 2011 and will dramatically increase the likelihood of other diseases, such as heart diseases, kidney failure, nervous system diseases, etc. We pioneered the employment of an electrospun composite scaffold of polycaprolactone (PCL) and poliglecaprone (PGC) as the delivery vehicle for syngeneic murine islet transplantation to improve the clinical performance of islet transplantation in diabetic patients. PGC and PCL are both FDA approved degradable suture materials and the composite scaffold is expected to provide a temporal structural support for the islet population to integrate with the host. Our investigation showed that the scaffold increased the proliferation of transplanted islets and their ability to regulate blood glucose and glomerular functions in diabetic mice compared to those that received freely injected islets. A mechanistic study revealed that monocytes chemoattractant protein-1 (MCP-1) was responsible for this improvement, suggesting a promising therapeutic candidate in future renal tissue engineering strategy for diabetes
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