PMID- 23451253 OWN - NLM STAT- MEDLINE DCOM- 20140121 LR - 20240318 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 2 DP - 2013 TI - The therapeutic role of monocyte chemoattractant protein-1 in a renal tissue engineering strategy for diabetic patients. PG - e57635 LID - 10.1371/journal.pone.0057635 [doi] LID - e57635 AB - 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. FAU - Yin, Hao AU - Yin H AD - Department of Surgery, Shanghai Changzheng Hospital, Shanghai Second Military Medical University, Shanghai, China. FAU - Gao, Ming AU - Gao M FAU - Leoni, Lara AU - Leoni L FAU - Han, Huifang AU - Han H FAU - Zhang, Xing AU - Zhang X FAU - Fu, Zhiren AU - Fu Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130225 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Blood Glucose) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Insulin) SB - IM MH - Animals MH - Blood Glucose/metabolism MH - Chemokine CCL2/*metabolism/*pharmacology MH - Diabetes Mellitus, Experimental/blood/*surgery MH - Humans MH - Insulin/metabolism MH - Islets of Langerhans/metabolism/physiology MH - Islets of Langerhans Transplantation/*methods MH - Kidney/*surgery MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Tissue Engineering/*methods PMC - PMC3581514 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/03/02 06:00 MHDA- 2014/01/22 06:00 PMCR- 2013/02/25 CRDT- 2013/03/02 06:00 PHST- 2012/08/19 00:00 [received] PHST- 2013/01/23 00:00 [accepted] PHST- 2013/03/02 06:00 [entrez] PHST- 2013/03/02 06:00 [pubmed] PHST- 2014/01/22 06:00 [medline] PHST- 2013/02/25 00:00 [pmc-release] AID - PONE-D-12-26292 [pii] AID - 10.1371/journal.pone.0057635 [doi] PST - ppublish SO - PLoS One. 2013;8(2):e57635. doi: 10.1371/journal.pone.0057635. Epub 2013 Feb 25.