Mesenchymal stem cells protect islets from hypoxia/reoxygenation-induced injury.
Hypoxia/reoxygenation (H/R)-induced injury is the key factor associated with islet graft dysfunction. This study aims to examine the effect of mesenchymal stem cells (MSCs) on islet survival and insulin secretion under H/R conditions. Islets from rats were isolated, purified, cultured with or without MSCs, and exposed to hypoxia (O(2) ≤ 1%) for 8 h and reoxygenation for 24 and 48 h, respectively. Islet function was evaluated by measuring basal and glucose-stimulated insulin secretion (GSIS). Apoptotic islet cells were quantified using Annexin V-FITC. Anti-apoptotic effects were confirmed by mRNA expression analysis of hypoxia-resistant molecules, HIF-1α, HO-1, and COX-2, using semi-quantitative retrieval polymerase chain reaction (RT-PCR). Insulin expression in the implanted islets was detected by immunohistological analysis. The main results show that the stimulation index (SI) of GSIS was maintained at higher levels in islets co-cultured with MSCs. The MSCs protected the islets from H/R-induced injury by decreasing the apoptotic cell ratio and increasing HIF-1α, HO-1, and COX-2 mRNA expression. Seven days after islet transplantation, insulin expression in the MSC-islets group significantly differed from that of the islets-alone group. We proposed that MSCs could promote anti-apoptotic gene expression by enhancing their resistance to H/R-induced apoptosis and dysfunction. This study provides an experimental basis for therapeutic strategies based on enhancing islet function.
Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China. luyanrong@scu.edu.cn
Yanrong
Y
Lu
Xi
X
Jin
Younan
Y
Chen
Shengfu
S
Li
Yu
Y
Yuan
Gang
G
Mai
Bole
B
Tian
Dan
D
Long
Jie
J
Zhang
Li
L
Zeng
Youping
Y
Li
Jingqiu
J
Cheng
D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D007328:Insulin / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D010100:Oxygen / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D010100:Oxygen