16 Mesenchymal Stem Cells of Human Adult Bone Marrow
16 Mesenchymal Stem Cells of Human Adult Bone Marrow
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16 人类成人骨髓间充质干细胞
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
D. Marshak
中科院分区：
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作者：
M. Pittenger;D. Marshak
我们将干细胞广义地定义为产生具有一种以上分化表型的后代并且可以以未分化形式极大扩增的那些细胞。这不同于“祖细胞”，其仅产生单细胞谱系。从骨髓中分离人间充质干细胞（hMSC）并离体扩增。使用许多不同表面标志物的流式细胞术已证明扩增的群体>98%同质，并且在定义的体外试验中，这些细胞容易分化为多种结缔组织谱系，包括成骨细胞、软骨细胞和脂肪细胞（图1）（Pittenger et al. 1999）。这些细胞在原位位点的体内植入也将产生这些谱系中的组织。此外，培养的hMSC产生或可被诱导产生细胞因子以支持造血细胞（Majumdar等1998; Cheng等2000）。MSC与造血干细胞（HSC）的共培养证明，hMSC或成脂hMSC可以支持HSC的体外维持，甚至扩增，表明hMSC充当功能性基质（Thiede等人，2000）。此外，已经报道了产生大鼠MSC的肌源性分化的条件（Saito等，1995），并且hMSC显示出类似的行为，但可能效率较低。具有类似潜力的MSC也已从其他物种中分离出来，并且从兔中分离的MSC分化为腱细胞，以产生具有优异生物力学稳定性的切断肌腱的合适替代物（Young等人，1998）。兔骨髓间充质干细胞也显示出合适的软骨移植。
We define stem cells broadly as those cells that give rise to progeny with more than one differentiated phenotype and that may be greatly expanded in an undifferentiated form. This differs from a “progenitor cell,” which gives rise to a single cell lineage only. Human mesenchymal stem cells (hMSCs) are isolated from bone marrow and expanded ex vivo. Flow cytometry using many different surface markers has demonstrated the expanded population to be >98% homogeneous and in defined in vitro assays these cells readily differentiate to multiple connective tissue lineages, including osteoblasts, chondrocytes, and adipocytes (Fig. 1) (Pittenger et al. 1999). In vivo implantation of these cells at orthotopic sites will also yield tissues in these lineages. Additionally, cultured hMSCs either produce, or can be induced to produce, cytokines for support of hematopoietic cells (Majumdar et al. 1998; Cheng et al. 2000). Cocultures of the MSCs with hematopoietic stem cells (HSCs) demonstrated that hMSCs or adipogenic hMSCs can support the in vitro maintenance, and even expansion, of HSCs, suggesting hMSCs serve as functional stroma (Thiede et al. 2000). In addition, conditions that produce myogenic differentiation of rat MSCs have been reported (Saito et al. 1995), and hMSCs show similar behavior but perhaps less efficiently. MSCs with similar potential have been isolated from other species as well, and those isolated from rabbits differentiated to tenocytes to produce a suitable replacement for severed tendon with excellent biomechanical stability (Young et al. 1998). The rabbit MSCs were also shown to form suitable cartilaginous grafts...