Fukada So-ichiro, Miyagoe-Suzuki Yuko, Tsukihara Hiroshi, Yuasa Katsutoshi, Higuchi Saito, Ono Shiro, Tsujikawa Kazutake, Takeda Shin'ichi, Yamamoto Hiroshi
Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
J Cell Sci. 2002 Mar 15;115(Pt 6):1285-93. doi: 10.1242/jcs.115.6.1285.
The myogenic potential of bone marrow and fetal liver cells was examined using donor cells from green fluorescent protein (GFP)-gene transgenic mice transferred into chimeric mice. Lethally irradiated X-chromosome-linked muscular dystrophy (mdx) mice receiving bone marrow cells from the transgenic mice exhibited significant numbers of fluorescence(+) and dystrophin(+) muscle fibres. In order to compare the generating capacity of fetal liver cells with bone marrow cells in neonatal chimeras, these two cell types from the transgenic mice were injected into busulfantreated normal or mdx neonatal mice, and muscular generation in the chimeras was examined. Cardiotoxin-induced (or -uninduced, for mdx recipients) muscle regeneration in chimeras also produced fluorescence(+) muscle fibres. The muscle reconstitution efficiency of the bone marrow cells was almost equal to that of fetal liver cells. However, the myogenic cell frequency was higher in fetal livers than in bone marrow. Among the neonatal chimeras of normal recipients, several fibres expressed the fluorescence in the cardiotoxin-untreated muscle. Moreover, fluorescence(+) mononuclear cells were observed beneath the basal lamina of the cardiotoxin-untreated muscle of chimeras, a position where satellite cells are localizing. It was also found that mononuclear fluorescence(+) and desmin(+) cells were observed in the explantation cultures of untreated muscles of neonatal chimeras. The fluorescence(+) muscle fibres were generated in the second recipient mice receiving muscle single cells from the cardiotoxin-untreated neonatal chimeras. The results suggest that both bone marrow and fetal liver cells may have the potential to differentiate into muscle satellite cells and participate in muscle regeneration after muscle damage as well as in physiological muscle generation.
利用从绿色荧光蛋白(GFP)基因转基因小鼠获取的供体细胞,将其移植到嵌合小鼠体内,以此检测骨髓细胞和胎肝细胞的生肌潜能。接受转基因小鼠骨髓细胞的经致死剂量照射的X染色体连锁型肌营养不良(mdx)小鼠,出现了大量荧光(+)和抗肌萎缩蛋白(+)的肌纤维。为了比较新生嵌合体中胎肝细胞与骨髓细胞的生成能力,将来自转基因小鼠的这两种细胞类型注射到经白消安处理的正常或mdx新生小鼠体内,并检测嵌合体中的肌肉生成情况。嵌合体中由心脏毒素诱导(或对于mdx受体小鼠为未诱导)的肌肉再生也产生了荧光(+)的肌纤维。骨髓细胞的肌肉重建效率几乎与胎肝细胞相同。然而,胎肝中的生肌细胞频率高于骨髓。在正常受体的新生嵌合体中,在未经心脏毒素处理的肌肉中有几根纤维表达荧光。此外,在嵌合体未经心脏毒素处理的肌肉的基膜下方观察到荧光(+)单核细胞,这是卫星细胞所在的位置。还发现,在新生嵌合体未经处理的肌肉的外植体培养物中观察到单核荧光(+)和结蛋白(+)细胞。在接受来自未经心脏毒素处理的新生嵌合体的肌肉单细胞的第二代受体小鼠中产生了荧光(+)肌纤维。结果表明,骨髓细胞和胎肝细胞都可能具有分化为肌肉卫星细胞的潜能,并在肌肉损伤后参与肌肉再生以及生理性肌肉生成。