Identification and characterization of chondrogenic progenitor cells in the fascia of postnatal skeletal muscle

Identification and characterization of chondrogenic progenitor cells in the fascia of postnatal skeletal muscle
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DOI:
10.1093/jmcb/mjr014
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发表时间:
2011-12-01
影响因子:
5.5
通讯作者:
Huard, Johnny
Huard, Johnny
中科院分区:
生物学1区
文献类型:
--
作者:
Li, Guangheng;Zheng, Bo;Huard, Johnny

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肌内注射骨形态发生蛋白(BMP)已被证明可诱导异位骨形成。在此过程中通常观察到软骨形成阶段,这表明可能存在驻留在骨骼肌中的软骨形成细胞亚群。从大鼠骨骼肌中分离出两种预期的细胞群:从臀大肌筋膜(肌外膜)中提取的筋膜衍生细胞(FDC)和从肌肉体中分离的肌肉衍生细胞(MDC)。研究了这两个群体的细胞表面标志物特征(流式细胞术分析)、增殖率以及其成肌和成软骨潜力。大多数FDCs表达间充质基质细胞标志物,但不表达内皮细胞标志物。在体外,BMP 4处理后,FDCs经历软骨分化,但不经历肌分化。虽然MDCs显示出软骨形成潜力,但它们表达成肌细胞标志物结蛋白,并且在体外容易进行成肌分化;然而,MDCs的软骨形成潜力被存在于肌肉肌束膜和肌内膜中的FDC样细胞所混淆。为了阐明肌肉来源的肌源性细胞在软骨形成中的作用,形成了具有不同比例的FDC和L 6成肌细胞的混合颗粒,并研究了其软骨形成潜力。我们的研究结果表明,混合颗粒的软骨形成潜力随着成肌细胞与FDC比例的增加而降低,这支持了FDC在软骨形成中的作用。总之,我们的研究结果表明,非肌源性细胞驻留在骨骼肌筋膜有很强的软骨形成的潜力,并可能代表一种新的供体细胞来源的软骨再生和修复。
Intramuscular injection of bone morphogenetic proteins (BMPs) has been shown to induce ectopic bone formation. A chondrogenic phase is typically observed in this process, which suggests that there may exist a chondrogenic subpopulation of cells residing in skeletal muscle. Two prospective cell populations were isolated from rat skeletal muscle: fascia-derived cells (FDCs), extracted from gluteus maximus muscle fascia (epimysium) and muscle-derived cells (MDCs) isolated from the muscle body. Both populations were investigated for their cell surface marker profiles (flowcytometry analysis), proliferation rates as well as their myogenic and chondrogenic potentials. The majority of FDCs expressed mesenchymal stromal cell markers but not endothelial cell markers. FDCs underwent chondrogenic differentiation after BMP4 treatment in vitro, but not myogenic differentiation. Although MDCs showed chondrogenic potential, they expressed the myogenic cell marker desmin and readily underwent myogenic differentiation in vitro; however, the chondrogenic potential of the MDCs is confounded by the presence of FDC-like cells residing in the muscle perimysium and endomysium. To clarify the role of the muscle-derived myogenic cells in chondrogenesis, mixed pellets with varying ratios of FDCs and L6 myoblasts were formed and studied for chondrogenic potential. Our results indicated that the chondrogenic potential of the mixed pellets decreased with the increased ratio of myogenic cells to FDCs supporting the role of FDCs in chondrogenesis. Taken together, our results suggest that non-myogenic cells residing in the fascia of skeletal muscle have a strong chondrogenic potential and may represent a novel donor cell source for cartilage regeneration and repair.