Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration.

Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration.
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DOI:
10.1016/j.stem.2012.02.003
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发表时间:
2012-03-02
期刊:
影响因子:
23.9
通讯作者:
Scadden, David T.
Scadden, David T.
中科院分区:
医学1区
文献类型:
--
作者:
Park, Dongsu;Spencer, Joel A.;Koh, Bong Ihn;Kobayashi, Tatsuya;Fujisaki, Joji;Clemens, Thomas L.;Lin, Charles P.;Kronenberg, Henry M.;Scadden, David T.

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间充质干细胞(MSCs)通常被定义为体外功能,尽管其在体内的功能很少被定义,但已进入临床应用。在这里,我们报告了遗传脉冲追踪实验,该实验将成骨细胞定义为寿命短且不可复制的细胞,需要从骨髓来源的具有“MSC”特征的Mx1+基质细胞中补充。这些细胞对组织应激作出反应并迁移到损伤部位,在骨折愈合过程中提供新的成骨细胞。单细胞移植产生的后代既能保留祖细胞的功能,又能分化成成骨细胞,产生新骨。它们具有局部和全身移位和连续移植的能力。虽然这些细胞在体外符合目前MSCs的定义,但它们在生长和成年动物体内的骨脂化受到限制。因此,骨髓来源的间充质干细胞可能是一个具有Mx1+群体的异质群体,代表了一个高度动态和应激反应的干细胞/祖细胞群体,具有命运限制的潜力,可以满足成人骨骼的高细胞替换需求。
Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical application despite little definition of their function in residence. Here, we report genetic pulse-chase experiments that define osteoblastic cells as short-lived and nonreplicative, requiring replenishment from bone-marrow-derived, Mx1+ stromal cells with “MSC” features. These cells respond to tissue stress and migrate to sites of injury, supplying new osteoblasts during fracture healing. Single cell transplantation yielded progeny that both preserve progenitor function and differentiate into osteoblasts, producing new bone. They are capable of local and systemic translocation and serial transplantation. While these cells meet current definitions of MSCs in vitro, they are osteolineage restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived MSCs may be a heterogeneous population with the Mx1+ population, representing a highly dynamic and stress responsive stem/progenitor cell population of fate-restricted potential that feeds the high cell replacement demands of the adult skeleton.
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