The effect of heme oxygenase-1 complexed with collagen on MSC performance in the treatment of diabetic ischemic ulcer
The effect of heme oxygenase-1 complexed with collagen on MSC performance in the treatment of diabetic ischemic ulcer
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血红素加氧酶-1与胶原蛋白复合对糖尿病缺血性溃疡治疗中MSC性能的影响
DOI：
10.1016/j.biomaterials.2012.09.022
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发表时间：
2013-01-01
期刊：
影响因子：
14
通讯作者：
Zhu, Chuhong
中科院分区：
文献类型：
--
作者：
Hou, Chunli;Shen, Lei;Zhu, Chuhong
糖尿病缺血性溃疡是一种难治性糖尿病并发症。骨髓间充质干细胞（BMSCs）在多种组织修复中具有巨大的潜力。事实上，差的细胞活力和耐受性限制了它们的组织修复能力。此外，干细胞很难归巢并定位到病变。在这项研究中，我们探讨是否血红素氧合酶-1（HO-1）在BMSCs复合胶原蛋白中的过度表达在糖尿病缺血性溃疡的治疗中发挥重要作用。HO-1的过表达促进BMSCs的增殖和旁分泌活性，BMSCs条件培养液促进HUVECs的迁移和增殖。这些过程与Akt信号通路密切相关，不依赖于Erk信号通路。在体内，为了使BMSCs直接作用于创面，我们选择固体胶原蛋白作为载体，将BMSCs种植于其中，将BMSCs与胶原蛋白复合物覆盖于糖尿病小鼠缺血创面。结果表明，过表达HO-1的BMSCs与胶原生物材料的复合物可以显著促进血管生成和伤口愈合。这些临床前发现为糖尿病足溃疡的治疗开辟了新的前景。(C)2012爱思唯尔有限公司保留所有权利。
Diabetic ischemic ulcer is an intractable diabetic complication. Bone marrow mesenchymal stem cells (BMSCs) have great potential in variety of tissue repair. In fact, poor cell viability and tolerance limit their ability for tissue repair. In addition, it is difficult for stem cells to home and locate to the lesion. In this study, we explore whether over-expression of heme oxygenase-1 (HO-1) in BMSCs complexed with collagen play an important role in treatment of diabetic ischemic ulcers. In vitro, over-expression of HO-1 promoted the proliferation and paracrine activity of BMSCs and the conditioned medium of BMSCs accelerated HUVECs migration and proliferation. These processes were closely related to Akt signaling pathway and were not dependent on Erk signaling pathway. In vivo, in order to make BMSCs directly act on the wound, we choose a solid collagen as a carrier, BMSCs were planted into it, ischemic wounds of diabetic mice were covered with the complex of BMSCs and collagen. The results indicate that the complex of HO-1-overexpressing BMSCs and collagen biomaterials can significantly promote angiogenesis and wound healing. These preclinical findings open new perspectives for the treatment of diabetic foot ulcers. (C) 2012 Elsevier Ltd. All rights reserved.