Mechanisms of muscle stem cell expansion with cytokines
Mechanisms of muscle stem cell expansion with cytokines
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DOI：
10.1634/stemcells.20-1-50
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发表时间：
2002-01-01
期刊：
影响因子：
5.2
通讯作者：
Huard, J
中科院分区：
文献类型：
--
作者：
Deasy, BM;Qu-Peterson, Z;Huard, J
干细胞的扩增和增殖对于细胞移植和干细胞介导的应用是重要的。虽然我们已经证明肌肉干细胞可以从成人骨骼肌组织中获得，但这些细胞仅占肌肉来源细胞的一小部分，并且需要体外扩增才能成功进行干细胞介导的治疗。在这项研究中，我们通过将非指数数学模型与独特的细胞培养系统相结合，研究了几种细胞因子刺激干细胞生长的潜力。在添加了表皮生长因子（EGF）、成纤维细胞生长因子-2 （FGF-2）、胰岛素样生长因子-1 （IGF-1）、FLT-3配体、肝细胞生长因子或干细胞因子（SCF）的培养基中，研究了两组肌肉干细胞的生长动力学。以分裂时间（DT）和有丝分裂活性细胞的比例为关键参数，进一步了解stein细胞群体扩增的机制。我们的研究结果表明，在EGF、IGF-1和SCF存在的情况下，新分离的肌肉源性干细胞（MDSC）通过将细胞招募到细胞周期中而发生扩增。然而，培养的干细胞克隆MC13的扩增归因于FGF-2、EGF、IGF-1和SCF存在时细胞周期长度的缩短。FLT-3配体通过增加细胞周期长度来抑制MDSC和MC13的生长。我们的研究结果表明，EGF、IGF-1、FGF-2和SCIF是刺激MDSC增殖的重要细胞因子。此外，本研究表明，干细胞的扩增通过不同的机制发生，因此证明了在生长因子刺激后监测细胞生长的几个参数（如DT和分裂分数）的重要性。
Stem cell expansion and proliferation are important for cell transplantation and stem cell-mediated applications. While we have demonstrated that muscle stem cells can be obtained from adult skeletal muscle tissue, these cells represent only a small percentage of the muscle-derived cells and require in vitro expansion for successful stem cell-mediated therapies. In this study, we have examined the potential of several cytokines to stimulate stem cell growth by combining a non-exponential mathematical model with a unique cell culture system. The growth kinetics of two populations of muscle stem cells were characterized in culture medium supplemented with epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1), FLT-3 ligand, hepatocyte growth factor, or stem cell factor (SCF). The division time (DT) and fraction of mitotically active cells were investigated as key parameters to further understand the mechanism of the expansion of the stein cell populations. Our results, show that expansion of the freshly isolated, muscle-derived stem cells (MDSC) occurred by recruiting cells into the cell cycle in the presence of EGF, IGF-1, and SCF. However, expansion of the cultured stem cell clone, MC13, is attributed to a reduction of the length of the cell cycle in the presence of FGF-2, EGF, IGF-1, and SCF. Both MDSC and MC13 growth were inhibited in the presence of FLT-3 ligand by increasing the length of the cell cycle. Our results suggest that EGF, IGF-1, FGF-2, and SCIF are important cytokines for stimulating the proliferation of MDSC. In addition, this study illustrates that expansion of stem cells, occurs through different mechanisms, which consequently demonstrates the importance of monitoring several parameters of cell growth, such as DT and dividing fraction, following stimulation with growth factors.