Farace Francoise, Prestoz Laetitita, Badaoui Sabrina, Guillier Martine, Haond Celine, Opolon Paule, Thomas Jean-Leon, Zalc Bernard, Vainchenker William, Turhan Ali G
Translational Research-Cell Therapy Laboratory, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France.
Stem Cells Dev. 2004 Feb;13(1):83-92. doi: 10.1089/154732804773099281.
Muscle tissue of adult mice has been shown to contain stem cells with hematopoietic repopulation ability in vivo. To determine the functional characteristics of stem cells giving rise to this hematopoietic activity, we have performed hematopoietic reconstitution experiments by the use of muscle versus marrow transplantation in lethally irradiated mice and followed the fate of transplanted cells by Y-chimerism using PCR and fluorescence in situ hybridization (FISH) analysis. We report here that transplantation of murine muscle generate a major hematopoietic chimerism at the level of CFU-C, CFU-S, and terminally-differentiated cells in three generations of lethally irradiated mice followed up to 1 year after transplantation. This potential is totally abolished when muscle grafts were performed by the use of muscle from previously irradiated mice. As compared to marrow transplantation, muscle transplants were able to generate similar potencies to give rise to myeloid, T, B, and natural killer (NK) cells. Interestingly, marrow stem cells that have been generated in primary and then in secondary recipients were able to contribute efficiently to myofibers in the muscle tissue of tertiary recipients. Altogether, our data demonstrate that muscle-derived stem cells present a major hematopoietic repopulating ability with evidence of self-replication in vivo. They are radiation-sensitive and similar to marrow-derived stem cells in terms of their ability to generate multilineage hematopoiesis. Finally, our data demonstrate that muscle-derived hematopoietic stem cells do not lose their ability to contribute to myofiber generation after at least two rounds of serial transplantation, suggesting a potential that is probably equivalent to that generated by marrow transplantation.
已证明成年小鼠的肌肉组织含有在体内具有造血重建能力的干细胞。为了确定产生这种造血活性的干细胞的功能特性，我们通过在致死性照射的小鼠中进行肌肉移植与骨髓移植的造血重建实验，并使用PCR和荧光原位杂交（FISH）分析通过Y染色体嵌合来追踪移植细胞的命运。我们在此报告，在移植后长达1年的三代致死性照射小鼠中，小鼠肌肉移植在CFU-C、CFU-S和终末分化细胞水平产生了主要的造血嵌合。当使用先前照射过的小鼠的肌肉进行肌肉移植时，这种潜能完全丧失。与骨髓移植相比，肌肉移植能够产生类似的潜能来产生髓系、T、B和自然杀伤（NK）细胞。有趣的是，在初代和二代受体中产生的骨髓干细胞能够有效地参与三代受体肌肉组织中的肌纤维形成。总之，我们的数据表明，肌肉来源的干细胞具有主要的造血重建能力，并在体内有自我复制的证据。它们对辐射敏感，在产生多谱系造血的能力方面与骨髓来源的干细胞相似。最后，我们的数据表明，肌肉来源的造血干细胞在至少两轮连续移植后不会丧失其对肌纤维生成的贡献能力，这表明其潜能可能与骨髓移植产生的潜能相当。
