Bone marrow stromal cells (BMSCs) in bone engineering: Limitations and recent advances
Bone marrow stromal cells (BMSCs) in bone engineering: Limitations and recent advances
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DOI：
10.1023/b:abme.0000007800.89194.95
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发表时间：
2004-01-01
影响因子：
3.8
通讯作者：
Cancedda, R
中科院分区：
文献类型：
--
作者：
Derubeis, AR;Cancedda, R
骨髓基质细胞（BMSCs）是Friedenstein等首次分离得到的，此后被认为是骨骼组织的祖细胞。事实上，BMSC是克隆形成的，成纤维细胞的形状，并可以沿着多种谱系分化，如成骨细胞，软骨细胞，脂肪细胞和造血支持基质。当在免疫功能低下的小鼠体内植入三维生物陶瓷支架时，BMSC形成骨和造血支持基质。骨髓间充质干细胞易于从供体骨髓中获得，并具有体内形成骨的能力，这使得骨髓间充质干细胞成为临床应用的理想选择。因此，体外扩增的BMSC已被用于，首先在大型动物模型中，然后在人类临床试验中，以修复大段骨缺损。对扩增的BMSC群体的进一步研究导致观察到体外扩增似乎是限制性的传代：细胞倾向于衰老并随着培养时间的推移失去其多分化潜能。为了克服这些限制，已经提出了两种方法：（1）通过可能地选择具有干细胞特征的亚群来鉴定适当的培养条件以防止衰老，和（2）通过用端粒酶基因转染来工程化细胞以防止细胞端粒缩短和随之而来的衰老。
Bone marrow stromal cells (BMSCs) have been isolated for the first time by Friedenstein et al. and since then have been considered the progenitor cells for the skeletal tissues. Indeed BMSCs are clonogenic, fibroblastic in shape, and can differentiate along multiple lineages such as osteoblasts, chondrocytes, adipocytes, and hematopoiesis-supportive stroma. When implanted in vivo on a three-dimensional bioceramic scaffold into immunocompromised mice, BMSCs form bone and hematopoiesis-supportive stroma. The ease of harvest from a donor bone marrow together with the ability to form bone in vivo make BMSCs ideal for clinical applications. Thus, ex vivo expanded BMSCs have been employed, first in large animal models, then in human clinical trials, to repair large bone segmental defects. Further investigation of the expanded BMSC population led to the observation that in vitro expansion appears a limiting passage: cells tend to senesce and lose their multidifferentiation potential with time in culture. To overcome these limitations, two approaches have been proposed: (1) identification of the appropriate culture conditions to prevent senescence by possibly selecting a subpopulation with stem cell characteristics, and (2) engineering of the cells by transfection with the telomerase gene to prevent cells from telomere shortening and consequent aging.