Hematopoietic potential of stem cells isolated from murine skeletal muscle
Hematopoietic potential of stem cells isolated from murine skeletal muscle
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DOI：
10.1073/pnas.96.25.14482
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发表时间：
1999-12-07
影响因子：
11.1
通讯作者：
Goodell, MA
中科院分区：
文献类型：
--
作者：
Jackson, KA;Mi, TJ;Goodell, MA
我们发现成年小鼠骨骼肌来源的细胞具有显著的造血分化能力，用酶消化法和体外培养5天获得肌肉来源的细胞，并将18×10(3)细胞与200×10(3)可分辨的全骨髓细胞一起导入6个致死照射的受者体内。6周或12周后，所有受者都表现出代表所有主要成人血统的肌肉来源细胞的高水平植入。肌肉细胞后代对外周血的平均总贡献率为56+/-20%(SD)，表明培养的肌肉细胞产生的造血活性大约是整个骨髓的10-14倍。当一只小鼠的骨髓被采集并移植到二次受者体内时，所有受者都表现出高水平的多系植入(平均40%)，确立了这些干细胞的极其原始的性质。我们还发现，肌肉中含有一群具有骨髓源性造血干细胞特征的细胞，包括荧光染料Hoechst 33342的高外流以及干细胞抗原SCA-L和E-Kit的表达，尽管这些细胞缺乏造血标志物CD45。我们认为，这一群体解释了培养的骨骼肌产生的造血活动。这些假定的干细胞可能与肌肉卫星细胞相同，其中一些缺乏生肌调节因子，有望对造血信号做出反应。
We have discovered that cells derived from the skeletal muscle of adult mice contain a remarkable capacity for hematopoietic differentiation, Cells prepared from muscle by enzymatic digestion and 5-day in vitro culture were harvested, and 18 x 10(3) cells were introduced into each of six lethally irradiated recipients together with 200 x 10(3) distinguishable whole bone marrow cells. After 6 or 12 weeks, all recipients showed high-level engraftment of muscle-derived cells representing all major adult blood lineages. The mean total contribution of muscle cell progeny to peripheral blood was 56 +/- 20% (SD), indicating that the cultured muscle cells generated approximately 10- to 14-fold more hematopoietic activity than whole bone marrow. When bone marrow from one mouse was harvested and transplanted into secondary recipients, all recipients showed high-level multilineage engraftment (mean 40%), establishing the extremely primitive nature of these stem cells. We also show that muscle contains a population of cells with several characteristics of bone marrow-derived hematopoietic stem cells, including high efflux of the fluorescent dye Hoechst 33342 and expression of the stem cell antigens Sca-l and E-Kit although the cells lack the hematopoietic marker CD45. We propose that this population accounts for the hematopoietic activity generated by cultured skeletal muscle. These putative stem cells may be identical to muscle satellite cells, some of which lack myogenic regulators and could be expected to respond to hematopoietic signals.