Bone Marrow-Derived Mesenchymal Stromal Cells Enhance Chimeric Vessel Development Driven by Endothelial Cell-Coated Microtissues
Bone Marrow-Derived Mesenchymal Stromal Cells Enhance Chimeric Vessel Development Driven by Endothelial Cell-Coated Microtissues
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DOI：
10.1089/ten.tea.2011.0393
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发表时间：
2012-02-01
影响因子：
4.1
通讯作者：
Sefton, Michael V.
中科院分区：
文献类型：
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作者：
Chamberlain, Michael Dean;Gupta, Rohini;Sefton, Michael V.
将骨髓来源的间充质基质细胞（bmMSCs）加入内皮化的胶原凝胶模块导致成熟的血管形成，部分原因可能是移植的GFP(+) bmMSCs表现出周细胞样行为。先前的研究发现，大鼠主动脉内皮细胞（RAECs）在小的（类似于0.8mm长x 0.5mm直径）胶原凝胶柱（微组织，模块化组织工程）表面递送到免疫抑制的Sprague-Dawley （SD）大鼠体内后形成血管。尽管raec在异体移植模型中形成了血管，但微计算机断层扫描（microCT）灌注研究显示，存在强烈的炎症反应，形成的血管是渗漏的。体外实验表明，嵌入胶原凝胶模块的SD大鼠bmMSCs可增加EC的增殖程度，并促进EC的发芽。在体内，虽然血管数量不受影响，但在微ct灌注分析中，bmMSCs和raec形成的新血管比单独植入raec形成的血管更稳定，渗漏更少。bmMSCs的加入还减少了浸润移植物的CD68（+）巨噬细胞的总数，改变了CD163(+) （M2）巨噬细胞的分布，从而在新形成的血管化组织中发现了它们。最有趣的是，bmMSCs变得平滑肌肌动蛋白阳性，并迁移到血管EC层周围，这是周细胞的典型位置。这两种作用的结合被认为是bmMSCs嵌入ec包覆模块时血管性改善的原因。对这些观察结果的进一步探索是有必要利用模块化组织工程作为使用微组织成分形成大型血管化功能组织的手段。
Adding bone marrow-derived mesenchymal stromal cells (bmMSCs) to endothelialized collagen gel modules resulted in mature vessel formation, presumably caused in part by the observed display of pericyte-like behavior for the transplanted GFP(+) bmMSCs. A previous study determined that rat aortic endothelial cells (RAECs) delivered on the surface of small (similar to 0.8mm long x 0.5mm diameter) collagen gel cylinders (microtissues, modular tissue engineering) formed vessels after transplantation into immunosuppressed Sprague-Dawley (SD) rats. Although the RAECs formed vessels in this allogeneic transplant model, there was a robust inflammatory response and the vessels that formed were leaky as shown by microcomputed tomography (microCT) perfusion studies. In vitro assays showed that SD rat bmMSCs embedded into the collagen gel modules increased the extent of EC proliferation and enhanced EC sprouting. In vivo, although vessel number was not affected, the new vessels formed by the bmMSCs and RAECs were more stable and leaked less in the microCT perfusion analysis than vessels formed by implanted RAECs alone. Addition of the bmMSCs also decreased the total number of CD68(+) macrophages that infiltrated the implant and changed the distribution of CD163(+) (M2) macrophages so that they were found within the newly developed vascularized tissue. Most interestingly, the bmMSCs became smooth muscle actin positive and migrated to surround the EC layer of the vessel, which is the location typical of pericytes. The combination of these two effects was presumed to be the cause of improved vascularity when bmMSCs were embedded in the EC-coated modules. Further exploration of these observations is warranted to exploit modular tissue engineering as a means of forming large vascularized functional tissues using microtissue components.