Department of Hand Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cell Prolif. 2019 Sep;52(5):e12660. doi: 10.1111/cpr.12660. Epub 2019 Jul 2.
Muscle spindles are proprioceptive receptors in the skeletal muscle. Peripheral nerve injury results in a decreased number of muscle spindles and their morphologic deterioration. However, the muscle spindles recover when skeletal muscles are reinnervated with surgical procedures, such as nerve suture or nerve transfer. Morphological changes in muscle spindles by cell transplantation procedure have not been reported so far. Therefore, we hypothesized that transplantation of embryonic sensory neurons may improve sensory neurons in the skeletal muscle and reinnervate the muscle spindles.
We collected sensory neurons from dorsal root ganglions of 14-day-old rat embryos and prepared a rat model of peripheral nerve injury by performing sciatic nerve transection and allowing for a period of one week before which we performed the cell transplantations. Six months later, the morphological changes of muscle spindles in the cell transplantation group were compared with the naïve control and surgical control groups.
Our results demonstrated that transplantation of embryonic dorsal root ganglion cells induced regeneration of sensory nerve fibre and reinnervation of muscle spindles in the skeletal muscle. Moreover, calbindin D-28k immunoreactivity in intrafusal muscle fibres was maintained for six months after denervation in the cell transplantation group, whereas it disappeared in the surgical control group.
Cell transplantation therapies could serve as selective targets to modulate mechanosensory function in the skeletal muscle.
肌梭是骨骼肌中的本体感受器。周围神经损伤会导致肌梭数量减少和形态恶化。然而,当骨骼肌通过手术(如神经缝合或神经转移)重新支配时,肌梭会恢复。到目前为止,还没有关于细胞移植过程中肌梭形态变化的报道。因此,我们假设胚胎感觉神经元的移植可能会改善骨骼肌中的感觉神经元并重新支配肌梭。
我们从 14 天大的大鼠胚胎背根神经节中收集感觉神经元,并通过切断坐骨神经来制备周围神经损伤大鼠模型,在进行细胞移植之前允许一周的时间。6 个月后,将细胞移植组的肌梭形态变化与未处理对照组和手术对照组进行比较。
我们的结果表明,胚胎背根神经节细胞的移植诱导了感觉神经纤维的再生和骨骼肌中肌梭的重新支配。此外,在细胞移植组中,去神经后 6 个月内肌梭内纤维的钙结合蛋白 D-28k 免疫反应性得以维持,而在手术对照组中则消失。
细胞移植疗法可以作为调节骨骼肌机械感觉功能的选择性靶标。