Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin on islets survival and function in vitr
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ORIGINAL PAPER
Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin on islets survival and function in vitro and in vivo Shu-yan Zhou & Yu-sen Zhang & Qing Li & Yi Zhang & Hui Qi & Han-xin Zhou & Chun-yan Deng & Fu-rong Li
Received: 28 December 2011 / Accepted: 16 May 2012 / Published online: 29 May 2012 # University of Navarra 2012
Abstract To maintain islets survival and function is critical in successful pancreatic transplantation. Pancreatic progenitors cells (PPCs) with lineage potentials, giving rise to exocrine, endocrine, and duct cells, reside in developing and adult pancreas. As tissuespecific stem cells, they can produce pancreatic tissue-specific matrix factors to promote islets survival and function. The aim of our research was to investigate the protective effect of rat pancreatic–duodenal homeobox 1 (Pdx1)+/nestin+ PPCs on islets. In vitro, co-culturing islets with Pdx1+/nestin+ PPCs prolonged the former survival from 7 to 14 days. Furthermore, with high glucose (300.8 mg/dl) stimuli, the yield of S.-y. Zhou : F.-r. Li Department of Pathology and Pathological Physiology, Medical College, Jinan University, Guangzhou 510632, People’s Republic of China S.-y. Zhou e-mail: [email protected] S.-y. Zhou : Y.-s. Zhang : Q. Li : Y. Zhang : H. Qi : H.-x. Zhou : C.-y. Deng : F.-r. Li (*) Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, No. 1017 Dong men North Road, Shenzhen 518020, People’s Republic of China e-mail: [email protected] Y.-s. Zhang e-mail: [email protected] Q. Li e-mail: [email protected]
insulin in co-cultures was significantly higher than that in control group (single islets group). In vivo, cotransplanting islets and Pdx1+/nestin+ PPCs for 3 days, the blood glucose of diabetic rat was significantly decreased to normal level and sustained for 2 weeks. Without Pdx1+/nestin+ PPCs in islets transplantation, hyperglycemia was reversed at day 7 and recovered at day 15. Pathology analysis showed that islets had remnants in co-transplantation at day 21, as complete graft rejection in alone islets transplantation. Our study showed that Pdx1+/nestin+ PPCs displayed the ability of preserving islets viability and function in vitro and prolonging their survival in vivo. Y. Zhang e-mail: [email protected] H. Qi e-mail: [email protected] H.-x. Zhou e-mail: [email protected] C.-y. Deng e-mail: [email protected] Y. Zhang The Pharmacy College, Jinan University, Guangzhou 510632, People’s Republic of China F.-r. Li Shenzhen Institution of Gerontology, Shenzhen 518020, People’s Republic of China
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Keywords Pancreatic progenitor cells . Pdx1 . Nestin . Islets . Co-culture . Co-transplantation
Introduction Edmonton protocol for pancreatic islet transplantation has focused intense interest in treating type 1 diabetes mellitus. However, basing on the present protocols, more than 30 % of donated islets appeared apoptotic during separation and purification. Scarcity of transplantable
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