Bone marrow mesenchymal stem cell transplantation improves ovarian function and structure in rats with chemotherapy-induced ovarian damage
Bone marrow mesenchymal stem cell transplantation improves ovarian function and structure in rats with chemotherapy-induced ovarian damage
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DOI：
10.1080/14653240802035926
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发表时间：
2008-01-01
期刊：
影响因子：
4.5
通讯作者：
Liu, W.
中科院分区：
文献类型：
--
作者：
Fu, X.;He, Y.;Liu, W.
背景：大量研究表明，骨髓间充质干细胞移植可以改善损伤组织的结构和功能。本研究旨在探讨骨髓间充质干细胞移植对化疗所致卵巢损伤的治疗效果。方法体外分离培养人骨髓间充质干细胞。采用酶联免疫吸附试验(ELISA)检测细胞因子血管内皮生长因子(VEGF)、肝细胞生长因子(HGF)和胰岛素样生长因子-1(IGF-1)的表达。将磷酰胺芥末(PM)加入颗粒细胞(GC)单独培养或与MSC共同培养的培养液中。Annexin-V和DNA片段化分析检测胃癌细胞凋亡。用环磷酰胺(CTX)诱导大鼠化疗所致的卵巢损伤。注射后，将绿色荧光蛋白(GFP)标记的MSC直接移植到双侧卵巢。分别于移植后2、4、6、8周处死大鼠。通过发情周期变化和性激素水平评价卵巢功能。计数卵泡数，TUNEL法检测GC细胞凋亡率。Western blotting检测Bcl2和Bax蛋白的表达。结果MSC在体外可释放血管内皮生长因子、肝细胞生长因子和胰岛素样生长因子-1。与MSC共培养可减少GC的凋亡，增加Bcl2的表达。骨髓间充质干细胞移植后注射环磷酰胺的大鼠卵巢功能明显改善。在体内，MSC可减少GC细胞的凋亡，并诱导Bcl2表达上调。探讨骨髓间充质干细胞移植可改善化疗所致的卵巢功能和结构损伤。MSC分泌的旁分泌介质可能参与了受损卵巢的修复。
Background Many investigations have reported that mesenchymal stem cell (MSC) transplantation can ameliorate the structure and function of injured tissues. The purpose of this study was to explore the therapeutic potency of MSC transplantation for chemotherapy-induced ovarian damage. Methods MSC were isolated and cultured in vitro. The cytokines, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1), were detected in the MSC cultures using enzyme-linked immunosorbent assay (ELISA). Phosphoramide mustard (PM) was added to the media of granulosa cells (GC) cultured alone or co-cultured with MSC. GC apoptosis was assayed by Annexin-V and DNA fragmentation analysis. Chemotherapy-induced ovarian damage was induced in rats by intraperitoneal injection of cyclophosphamide (CTX). After the injection, MSC labeled with green fluorescent protein (GFP) were transplanted directly into bilateral ovaries. The rats were killed at 2, 4, 6 and 8 weeks after transplantation. Ovarian function was evaluated by estrous cycle changes and sexual hormone levels. The follicle number was counted, and GC apoptosis was analyzed by TUNEL. The expressions of Bcl-2 and Bax proteins were detected by Western blotting. Results MSC released VEGF, HGF and IGF-1 in vitro. The GC apoptosis was diminished by co-culture with MSC, which also resulted in increased Bcl-2 expression. The ovarian function of the rats exposed to CTX injection was improved after MSC transplantation. MSC reduced apoptosis of GC and induced up-regulation of Bcl-2 in vivo. Discussion MSC transplantation can improve ovarian function and structure damaged by chemotherapy. The paracrine mediators secreted by MSC might be involved in the repair of damaged ovaries.