Bossolasco Patrizia, Corti Stefania, Strazzer Sandra, Borsotti Chiara, Del Bo Roberto, Fortunato Francesco, Salani Sabrina, Quirici Nadia, Bertolini Francesco, Gobbi Alberto, Deliliers Giorgio Lambertenghi, Pietro Comi Giacomo, Soligo Davide
Fondazione Matarelli, Ospedale Fatebenefratelli e Oftalmico, Milan, Italy.
Exp Cell Res. 2004 Apr 15;295(1):66-78. doi: 10.1016/j.yexcr.2003.12.015.
Murine bone marrow (BM) cells have been shown to undergo myogenic differentiation and participate in muscle repair in different muscle regeneration models. In the present paper, we report on a subset of cells (CD45+/desmin+) with myogenic potential being present at very low frequencies in human adult BM. By a simple culture method, we were able to obtain in vitro multinucleated myotubes in up to 20% of the cultures. Myotubes were generated using both BM flushed from rib fragments obtained during thoracotomy and BM derived from iliac crest aspirates. Cells of the different adherent and non-adherent fractions expressed numerous muscle specific markers by immunocytochemistry, real-time RT-PCR, flow cytometry, and Western blot analyses. Moreover, direct injection of whole BM into the right tibialis anterior muscle of immunodeficient mice (NOD/RAG) that had previously been treated with cardiotoxin to induce muscle degeneration, showed a variable but significant level of human cell engraftment (from 0.06 to 0.26% Dys+/FISH+ fibers). These data suggest that cells with skeletal muscle differentiation potential are present in adult human BM can differentiate in vitro and give rise to myogenic cells in vivo in immunodeficient mice after muscle damage. Further improvements might allow new approaches to cell-mediated therapies for muscular diseases.
在不同的肌肉再生模型中，已证明小鼠骨髓（BM）细胞可发生肌源性分化并参与肌肉修复。在本文中，我们报告了在人类成人骨髓中以极低频率存在的具有肌源性潜能的细胞亚群（CD45+/结蛋白+）。通过一种简单的培养方法，我们能够在高达20%的培养物中体外获得多核肌管。使用开胸手术期间从肋骨碎片冲洗得到的骨髓以及来自髂嵴抽吸物的骨髓均可生成肌管。通过免疫细胞化学、实时RT-PCR、流式细胞术和蛋白质印迹分析，不同贴壁和非贴壁部分的细胞表达了多种肌肉特异性标志物。此外，将全骨髓直接注射到先前用心脏毒素处理以诱导肌肉变性的免疫缺陷小鼠（NOD/RAG）的右胫前肌中，显示出不同但显著水平的人类细胞植入（0.06%至0.26%的Dys+/FISH+纤维）。这些数据表明，具有骨骼肌分化潜能的细胞存在于成人人类骨髓中，在体外可分化，并在免疫缺陷小鼠体内肌肉损伤后产生肌源性细胞。进一步的改进可能会为肌肉疾病的细胞介导治疗带来新方法。
