Determinants of skeletal muscle contributions from circulating cells, bone marrow cells, and hematopoietic stem cells
Determinants of skeletal muscle contributions from circulating cells, bone marrow cells, and hematopoietic stem cells
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DOI：
10.1634/stemcells.2004-0090
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发表时间：
2004-01-01
期刊：
影响因子：
5.2
通讯作者：
Wagers, AJ
中科院分区：
文献类型：
--
作者：
Sherwood, RI;Christensen, JL;Wagers, AJ
为了研究从未分离的骨髓(BM)细胞或高纯度的c-kit(+)Thy1.1(Lo)Lin-SCA-1(+)造血干细胞(HSCs)获得的供体标记物掺入未损伤或受损的骨骼肌的调节因素，我们评估了受照射和移植的受鼠以及未受照射的副生物动物中多肌群的肌纤维嵌合体。在BM或HSC移植后，未损伤的肌腱膜、横隔肌和腹肌很少将供体标记整合到肌纤维中；然而，急性肌肉损伤是诱发小腿三头肌(TS)和胫前肌的贡献的关键。表达供体标志物的肌纤维的低水平掺入既不能通过移植到新生儿受体中，也不能通过诱导HSCs向外周迁移来增强。对未受照射的异种异体动物的肌肉嵌合体的分析表明，TS中循环细胞对肌纤维的贡献是损伤相关的，至少有一些具有促进肌肉再生潜力的循环细胞来自骨髓，这表明这种贡献不需要清血预适应。在所有测试的病例中，供体来源的肌纤维都表达供体特异性和宿主特异性标记物，这表明它们是通过低水平融合到骨骼肌细胞中产生的，其中可能包括造血干细胞的后代。目前尚不清楚这些事件是代表正常的肌源性途径，还是代表对肌肉损伤的病理反应。
To investigate the factors that regulate incorporation into uninjured or damaged skeletal muscle of donor markers derived from unfractionated bone marrow (BM) cells or from highly purified c-kit(+)Thy1.1(lo)Lin-Sca-1(+) hematopoietic stem cells (HSCs), we evaluated myofiber chimerism of multiple muscle groups in irradiated and transplanted recipient mice and in unirradiated parabiotic animals. Uninjured panniculus carnosus, diaphragm, and abdominal muscles infrequently incorporated donor markers into myofibers in a subset of animals after either BM or HSC transplantation; however, acute muscle injury was essential to elicit contributions to triceps surae (TS) and tibialis anterior muscles. The low level of incorporation of donor marker-expressing myofibers could not be enhanced either by transplantation into newborn recipients or by induced migration of HSCs into the periphery. Analysis of muscle chimerism in unirradiated animals joined surgically by parabiosis revealed that contributions of circulating cells to myofibers in the TS were injury dependent and that at least some circulating cells with the potential to contribute to regenerating muscle derive from BM, suggesting that hematoablative preconditioning is not required for such contributions. In all cases tested, donor-derived myofibers expressed both donor-specific and host-specific markers, suggesting that they arise by low-level fusion into skeletal muscle of cells that can include the progeny of HSCs. It is not yet clear whether such events represent a normal myogenic pathway or a pathological response to muscle damage.