Adipose-derived stem cells improve erectile function partially through the secretion of IGF-1, bFGF, and VEGF in aged rats
Adipose-derived stem cells improve erectile function partially through the secretion of IGF-1, bFGF, and VEGF in aged rats
复制标题
脂肪干细胞通过分泌 IGF-1、bFGF 和 VEGF 部分改善老年大鼠的勃起功能
DOI：
10.1111/andr.12483
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发表时间：
2018-05-01
期刊：
影响因子：
4.5
通讯作者：
Liu, J.
中科院分区：
文献类型：
--
作者：
Yang, J.;Zhang, Y.;Liu, J.
脂肪源性干细胞（adipose-derived stem cells，ADSCs）是治疗勃起功能障碍（erectile dysfunction，艾德）的有效方法。然而，基于ADSC的治疗机制尚不清楚。胰岛素样生长因子-1（IGF-1），碱性成纤维细胞生长因子（bFGF），血管内皮生长因子（VEGF）的ADSCs分泌进行了评估体外。16只24月龄雄性Sprague-Dawley大鼠用于用标记的ADSC或PBS处理2周的比较分析。另外8只5月龄大鼠用作幼鼠组。移植后2周，分析所有大鼠的勃起功能、海绵体IGF-1、bFGF和VEGF水平以及阴茎组织学。采用条件培养基和共培养系统进行细胞实验，通过结晶紫染色和免疫荧光染色检测生长因子对氧化应激条件下阴茎海绵体平滑肌细胞（CCSMCs）的作用。我们发现，脂肪干细胞分泌显着较高的IGF-1，bFGF和VEGF水平在培养基中相比，基础培养基。与年轻大鼠相比，未治疗的老年大鼠的Max ICP/MAP显著降低，ADSC治疗显著增加了该比值。免疫荧光染色显示阴茎海绵体内有少量标记的脂肪干细胞。与青年大鼠相比，未治疗的老年大鼠海绵体IGF-1、bFGF和VEGF水平显著降低，海绵体平滑肌和内皮细胞含量显著降低。ADSC治疗使这些改变部分正常化。在细胞实验中，与对照组相比，单独或联合接受生长因子中和抗体的组具有显著减少的CCSMC数量。这些结果表明ADSC治疗可能部分通过分泌IGF-1、bFGF和VEGF来改善衰老相关的艾德。
Adipose-derived stem cells (ADSCs) have recently been considered as a promising therapy for erectile dysfunction (ED). However, the mechanism of ADSC-based therapy is unclear. Insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) secreted by ADSCs were assessed invitro. Sixteen 24-month-old male Sprague-Dawley rats were used for comparative analysis of 2-week treatment with labeled ADSCs or PBS. Eight additional 5-month-old rats were used as a young rat group. At 2weeks post-transplantation, all rats were analyzed for erectile function, cavernous IGF-1, bFGF and VEGF levels, and penile histology. Conditioned medium and co-culture systems were used in cell experiments to detect how growth factors act on corpus cavernosum smooth muscle cells (CCSMCs) under oxidative stress conditions via crystal violet staining and immunofluorescence staining. We found that ADSCs secreted significantly higher IGF-1, bFGF, and VEGF levels in culture medium compared with basal medium. Compared with young rats, untreated aged rats had significantly lower Max ICP/MAP and ADSC treatment significantly increased the ratio. Immunofluorescence staining demonstrated a small number of labeled ADSCs in the corpus cavernosum. The untreated aged rats showed significantly decreased cavernous IGF-1, bFGF, and VEGF levels and significantly decreased contents of cavernous smooth muscle and endothelium compared with young rats. ADSC treatment partially normalized these alterations. In cell experiments, the groups receiving growth factor neutralizing antibody separately or combined had significantly decreased numbers of CCSMCs compared with control groups. These results indicated that ADSC treatment may improve aging-related ED partially through the secretion of IGF-1, bFGF, and VEGF.