Pye D, Watt D J
Department of Neuromuscular Diseases, Imperial College School of Medicine, London, UK.
J Anat. 2001 Feb;198(Pt 2):163-73. doi: 10.1046/j.1469-7580.2001.19820163.x.
Both in vitro and in vivo studies have described the conversion of fibroblasts to myogenesis when in the presence of dysfunctional myogenic cells. Myogenic conversion of fibroblasts subjected to a normal, as opposed to a diseased muscle environment has only been reported in vitro. The primary aim of this work was to determine if fibroblasts can convert to a myogenic lineage and contribute to new fibre formation when implanted into the regenerating muscle of a normal mouse. Dermal fibroblasts were prepared from neonatal mouse skin and labelled prior to implantation with the fluorescent nuclear marker 4',6-diamidino-2-phenylindole (DAPI). Cells were implanted into muscles of host mice that had been subjected to either cold/crush or minced muscle injury. Some host muscles were x-irradiated to deplete the muscle of endogenous muscle precursor cells. Muscles were removed at 3 wk postimplantation and analysed both histologically and for the presence of DAPI labelled nuclei. Fibres containing DAPI labelled central nuclei indicated that the implanted cells had participated in the regenerative process. Mouse dermal fibroblasts therefore do contribute to muscle fibre formation in regenerating normal mouse muscle but the extent of their contribution is dependent on the nature of the trauma induced in the host muscle. The study also showed that regeneration was more successful in muscles which had not been irradiated, which is contrary to the previous studies where dermal fibroblasts were introduced into myopathic mouse muscle.
体外和体内研究均已描述,当存在功能失调的成肌细胞时,成纤维细胞会向成肌方向转化。与患病肌肉环境相反,在正常肌肉环境中,成纤维细胞的成肌转化仅在体外有报道。这项研究的主要目的是确定,当将成纤维细胞植入正常小鼠的再生肌肉中时,它们是否能转化为成肌谱系并促进新纤维的形成。从新生小鼠皮肤制备真皮成纤维细胞,并在植入前用荧光核标记物4',6-二脒基-2-苯基吲哚(DAPI)进行标记。将细胞植入遭受冷/挤压或肌肉切碎损伤的宿主小鼠的肌肉中。一些宿主肌肉接受了X射线照射,以耗尽肌肉中的内源性肌肉前体细胞。在植入后3周取出肌肉,进行组织学分析并检测是否存在DAPI标记的细胞核。含有DAPI标记的中央细胞核的纤维表明植入的细胞参与了再生过程。因此,小鼠真皮成纤维细胞确实有助于正常小鼠再生肌肉中的肌纤维形成,但其贡献程度取决于宿主肌肉中诱导的创伤性质。该研究还表明,未接受照射的肌肉再生更成功,这与之前将真皮成纤维细胞引入肌病小鼠肌肉的研究结果相反。