Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin on islets survival and function in vitro and in vivo.
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 tissue-specific 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 insulin in co-cultures was significantly higher than that in control group (single islets group). In vivo, co-transplanting 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.
Department of Pathology and Pathological Physiology, Medical College, Jinan University, Guangzhou 510632, People's Republic of China. zhoushuyan_xju2005@126.com
Shu-Yan
SY
Zhou
Yu-Sen
YS
Zhang
Qing
Q
Li
Yi
Y
Zhang
Hui
H
Qi
Han-Xin
HX
Zhou
Chun-Yan
CY
Deng
Fu-Rong
FR
Li
D000818:Animals; D001786:Blood Glucose; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010179:Pancreas / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein