Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs)
Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs)
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DOI：
10.1096/fj.07-087924
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发表时间：
2008-06-01
期刊：
影响因子：
4.8
通讯作者：
Niklason, Laura E.
中科院分区：
文献类型：
--
作者：
Gong, Zhaodi;Niklason, Laura E.
使用可生物降解的支架和仿生灌流系统，我们实验室成功地利用从不同物种的血管中获得的内皮细胞(ECs)和平滑肌细胞(SMC)设计了小直径血管移植物。然而，由于物种和年龄的差异，将这项技术移植到人类身上遇到了巨大的障碍。老年人来源的SMC增殖能力有限，胶原生成减少，这损害了工程血管的机械强度。以成人骨髓间充质干细胞(HMSCs)作为替代细胞来源，研究其在培养板和生物反应器系统中向SMC分化的能力。在前者中，免疫荧光染色显示，诱导14d后，MSCs分别表达SMC早期和中期的平滑肌α-肌动蛋白(SMA)和钙蛋白。在后一种情况下，用MSC来源的SMC构建血管壁。进一步研究了工程系统中的各种因素(即基质蛋白、可溶性因子和循环应变)对hMSC增殖和分化为SMC的影响。在多因素筛选的基础上，将血管培养分为增殖期和分化期，优化了工程体系。在优化的条件下设计的血管壁被组织学和分子学检查，发现与天然血管基本相似。综上所述，骨髓来源的hMSCs可作为血管工程中SMC的一种新的细胞来源。优化培养条件以促进SMC的分化和基质的产生，显著提高了hMSC来源的工程化血管壁的质量。
Using biodegradable scaffold and a biomimetic perfusion system, our lab has successfully engineered small-diameter vessel grafts using endothelial cells ( ECs) and smooth muscle cells (SMCs) obtained from vessels in various species. However, translating this technique into humans has presented tremendous obstacles due to species and age differences. SMCs from elderly persons have limited proliferative capacity and a reduction in collagen production, which impair the mechanical strength of engineered vessels. As an alternative cell source, adult human bone marrow-derived mesenchymal stem cells (hMSCs) were studied for their ability to differentiate into SMCs in culture plates as well as in a bioreactor system. In the former setting, immunofluorescence staining showed that MSCs, after induction for 14 days, expressed smooth muscle alpha-actin (SMA) and calponin, early and mid-SMC phenotypic markers, respectively. In the latter setting, vessel walls were constructed with MSC-derived SMCs. Various factors (i. e., matrix proteins, soluble factors, and cyclic strain) in the engineering system were further investigated for their effects on hMSC cell proliferation and differentiation into SMCs. Based on a screening of multiple factors, the engineering system was optimized by dividing the vessel culture into proliferation and differentiation phases. The vessel walls engineered under the optimized conditions were examined histologically and molecularly, and found to be substantially similar to native vessels. In conclusion, bone marrow-derived hMSCs can serve as a new cell source of SMCs in vessel engineering. Optimization of the culture conditions to drive SMC differentiation and matrix production significantly improved the quality of the hMSC-derived engineered vessel wall.