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RGD-Containing Elastin Like Polypeptide Improves Islet Transplantation Outcomes in Diabetic Mice Via Upregulation of Islet Survival and Vessel Formation

44 Pages Posted: 28 Jan 2019 Publication Status: Accepted

See all articles by Kyeong-Min Lee

Kyeong-Min Lee

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group

Jung-Hee Kim

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group

Eun-Sook Choi

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group

Eunjoo Kim

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group

Seong-Kyoon Choi

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Core Protein Resources Center

Won Bae Jeon

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group

Abstract

Successful islet transplantation critically depends on the isolation of healthy islets. Paradoxically, the islet isolation procedure contributes to islet death due to the destruction of intra- and peri-islet extracellular matrices (ECMs) during digestion. We investigated whether an RGD-containing elastin-like polypeptide named REP as a self-assembling matrix replenish damaged or missing ECMs and protects islet against cell death. Immediately following isolation, islets were coated with REP coacervate particles via isothermal adsorption of REP solution followed by thermal gelation. Both the viability and insulin secretory capacity of REP-coated islets were markedly increased during the pre-transplant culture, whereas control islets progressively lost viability and function. Co-transplantation of REP-treated islets and REP beneath the renal sub-capsule restored normoglycemia and serum insulin levels in streptozotocin-induced diabetic mice. Compared to islet-only transplants, mice that received co-transplants had a longer euglycemia maintenance time, sustained xenogeneic- and syngeneic- graft survival. Moreover, concomitant β-cell proliferation and generation of a rich vasculature were observed at the co-transplantation sites. In conclusion, the REP-based coacervation strategy provides great therapeutic potential for improving the ECMs for graft survival and functions, and most importantly to increase the outcomes of islet transplantation.

Keywords: RGD-containing elastin-like polypeptide, Protein coacervate, Islet transplantation, Islet survival, Insulin secretion

Suggested Citation

Lee, Kyeong-Min and Kim, Jung-Hee and Choi, Eun-Sook and Kim, Eunjoo and Choi, Seong-Kyoon and Jeon, Won Bae, RGD-Containing Elastin Like Polypeptide Improves Islet Transplantation Outcomes in Diabetic Mice Via Upregulation of Islet Survival and Vessel Formation (January 26, 2019). Available at SSRN: https://ssrn.com/abstract=3322821 or http://dx.doi.org/10.2139/ssrn.3322821

Kyeong-Min Lee

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group

Daegu Metropolitan City
Korea, Republic of (South Korea)

Jung-Hee Kim

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group

Daegu Metropolitan City
Korea, Republic of (South Korea)

Eun-Sook Choi

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group

Daegu Metropolitan City
Korea, Republic of (South Korea)

Eunjoo Kim

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group

Daegu Metropolitan City
Korea, Republic of (South Korea)

Seong-Kyoon Choi

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Core Protein Resources Center

Daegu Metropolitan City
Korea, Republic of (South Korea)

Won Bae Jeon (Contact Author)

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Companion Diagnostics and Medical Technology Research Group ( email )

Daegu Metropolitan City
Korea, Republic of (South Korea)

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