Mesenchymal stem cells protect islets from hypoxia/reoxygenation-induced injury.

Abstract

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.

• Authors: Yanrong Lu, Xi Jin, Younan Chen, Shengfu Li, Yu Yuan, Gang Mai, Bole Tian, Dan Long, Jie Zhang, Li Zeng, Youping Li, Jingqiu Cheng
• Journal: Cell biochemistry and function (Cell Biochem Funct) Vol. 28 Issue 8 Pg. 637-43 (Dec 02 2010) ISSN: 1099-0844 [Electronic] England
• PMID: 21061411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Oxygen

Topics

• Animals
• Apoptosis
• Cell Hypoxia
• Cell Survival
• Cells, Cultured
• Coculture Techniques
• Insulin (biosynthesis)
• Islets of Langerhans (cytology, physiology)
• Islets of Langerhans Transplantation
• Male
• Mesenchymal Stem Cells (cytology, physiology)
• Oxygen (administration & dosage)
• Rats
• Rats, Sprague-Dawley