Liu Jin Yu, Swartz Daniel D, Peng Hao Fan, Gugino Sylvia F, Russell James A, Andreadis Stelios T
Bioengineering Laboratory, 908 Furnas Hall, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, NY 14260, USA.
Cardiovasc Res. 2007 Aug 1;75(3):618-28. doi: 10.1016/j.cardiores.2007.04.018. Epub 2007 May 4.
Stem cells have significant potential for development of cell-based therapeutics for cardiovascular tissue regeneration.
We developed a novel method for isolating smooth muscle cells (SMC) from ovine bone marrow using a tissue-specific promoter and fluorescence-activated cell sorting.
As compared to vascular SMC, bone marrow-derived smooth muscle progenitor cells (BM-SMPC) exhibited similar morphology, showed higher proliferation potential and expressed several SMC markers including alpha-actin, calponin, myosin heavy chain, smoothelin, caldesmon and SM22. When embedded in fibrin hydrogels, BM-SMPC contracted the matrix and displayed receptor- and non-receptor-mediated contractility, indicating that BM-SMPC can generate force in response to vasoreactive agonists. We also prepared tissue-engineered blood vessels from BM-SMPC and BM-derived endothelial cells and implanted them into the jugular veins of lambs. As early as five weeks post-implantation, grafted tissues displayed a confluent endothelial layer overlaying the medial layer in which BM-SMPC were aligned circumferentially and synthesized significant amounts of collagen. In contrast to previous results with vascular SMC, BM-SMPC synthesized high amounts of elastin that was organized in a fibrillar network very similar to that of native vessels.
Our results suggest that BM-SMPC may be useful in studying SMC differentiation and have high potential for development of cell therapies for the treatment of cardiovascular disease.
干细胞在开发用于心血管组织再生的细胞疗法方面具有巨大潜力。
我们开发了一种利用组织特异性启动子和荧光激活细胞分选从绵羊骨髓中分离平滑肌细胞（SMC）的新方法。
与血管SMC相比，骨髓来源的平滑肌祖细胞（BM-SMPC）表现出相似的形态，具有更高的增殖潜力，并表达了几种SMC标志物，包括α-肌动蛋白、钙调蛋白、肌球蛋白重链、平滑肌蛋白、钙结合蛋白和SM22。当嵌入纤维蛋白水凝胶中时，BM-SMPC使基质收缩，并表现出受体介导和非受体介导的收缩性，表明BM-SMPC可响应血管活性激动剂产生力量。我们还从BM-SMPC和骨髓来源的内皮细胞制备了组织工程血管，并将其植入羔羊的颈静脉。早在植入后五周，移植组织就显示出在内膜层上覆盖有汇合的内皮细胞层，其中BM-SMPC沿圆周排列并合成了大量胶原蛋白。与先前使用血管SMC的结果相反，BM-SMPC合成了大量弹性蛋白，这些弹性蛋白组织成与天然血管非常相似的纤维状网络。
我们的结果表明，BM-SMPC可能有助于研究SMC分化，并在开发用于治疗心血管疾病的细胞疗法方面具有很高的潜力。
