A cellular delivery system fabricated with autologous BMSCs and collagen scaffold enhances angiogenesis and perfusion in ischemic hind limb.
A cellular delivery system fabricated with autologous BMSCs and collagen scaffold enhances angiogenesis and perfusion in ischemic hind limb.
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DOI：
10.1002/jbm.a.34081
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发表时间：
2012-06
期刊：
影响因子：
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通讯作者：
Jinling Wang;Wugeng Cui;Jianhong Ye;Shu-feng Ji;Xiu-qing Zhao;Linghui Zhan;Jiachun Feng;Zhigang Zhang;Yilin Zhao
中科院分区：
文献类型：
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作者：
Jinling Wang;Wugeng Cui;Jianhong Ye;Shu-feng Ji;Xiu-qing Zhao;Linghui Zhan;Jiachun Feng;Zhigang Zhang;Yilin Zhao
尽管治疗性细胞血管生成对慢性缺血是有效的，但细胞给药的最佳模式仍在探索中。本研究旨在开发一种细胞递送系统，以增强缺血后肢的血流灌注和血管生成。制备胶原支架(CS)，分离、扩增、筛选骨髓间充质干细胞(BMSCs)，接种于CS上，构建BMSCs-CS，用于形态和毒性分析。将自体BMSCs-CS、CS和自体BMSCs植入兔缺血模型的后肢，未治疗的缺血组或正常组作为缺血组或正常对照组。定期测量血氧饱和度参数，以确定肢体的血流灌注量。组织学检查采用苏木精-伊红-von Willebrand因子免疫组织化学染色和平滑肌(SM)α-肌动蛋白染色，以评估毛细血管和成熟血管。CS为多孔结构，无细胞毒性。在多个时段，正常对照组的血氧饱和度(OSR)最高。BMSCs-CS组和CS组OSR均高于BMSCs组和缺血对照组(p<；0.05)，6、8周时BMSCs-CS组OSR高于CS组(p<；0.05)。BMSCs-CS组和CS组的毛细血管数明显高于CS组、BMSCs组、缺血组和正常对照组(p<；0.05)。BMSCs-CS组的成熟血管数明显多于CS组、BMSCs组、缺血组和正常对照组(p<；0.05)。与单纯细胞治疗相比，自体细胞输送系统被证明是改善缺血程度较高的后肢血流和血管生成的有效方法。
Although therapeutic cellular angiogenesis is effective for chronic ischemia, the optimal mode of cellular administration is still under exploration. This study aimed to develop a cellular delivery system to enhance the perfusion and angiogenesis in the ischemic hind limb. Collagen scaffold (CS) was prepared, and for morphology and toxicity analysis, bone marrow-derived mesenchymal stem cells (BMSCs) were isolated, expanded, filtrated, and seeded onto CS to construct BMSCs-CS. The ischemic hind limbs of rabbit models were implanted with autologous BMSCs-CS, CS, and autologous BMSCs; the untreated ischemic or normal animals were considered as the ischemic or normal control groups. Oxygen saturation parameters were regularly measured to determine the perfusion in the extremities. Histological examinations with hematoxylin and eosin immunostaining against von Willebrand factor and smooth muscle (SM) α-actin were performed for capillary and mature vessel evaluation. CS was a multiporous structure without cytotoxicity. At several intervals, the oxygen saturation ratio (OSR) in normal control was the highest. The OSRs in BMSCs-CS and CS were higher than that in BMSCs and ischemic control (p < 0.05); the OSR in BMSCs-CS group was higher than that in CS at 6 and 8 weeks (p < 0.05). The capillaries in BMSCs-CS and CS were higher than that in CS, BMSCs, and the ischemic or normal control (p < 0.05). The mature vessels in BMSCs-CS were higher than that in CS, BMSCs, and the ischemic or normal control (p < 0.05). The autologous cellular delivery system proved to be an effective approach for improving higher ischemic hind limb perfusion and angiogenesis as opposed to cellular therapy alone.