The Synergistic Effect of Treadmill Running on Stem-Cell Transplantation to Heal Injured Skeletal Muscle
The Synergistic Effect of Treadmill Running on Stem-Cell Transplantation to Heal Injured Skeletal Muscle
复制标题
DOI：
10.1089/ten.tea.2009.0113
复制
发表时间：
2010-03-01
影响因子：
4.1
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
--
作者：
Ambrosio, Fabrisia;Ferrari, Ricardo J.;Huard, Johnny
肌源性干细胞（MDSC）移植为治疗肌肉损伤提供了一种有前途的方法。这项研究调查了运动增强 MDSC 移植到受伤肌肉的能力。将小鼠分为四组：挫伤 + 磷酸盐缓冲盐水组（C + PBS；n = 14 块肌肉）、C + MDSC 移植组（n = 12 块肌肉）、C + PBS + 跑步机组（C + PBS + TM；n = 17 块肌肉）和 C + MDSC + TM（n = 13 块肌肉）。受伤一天后，TM 组开始跑步 1 至 5 周。伤后两天，C+MDSC组和C+MDSC+TM组肌肉注射MDSC。 1 周或 5 周后，通过组织学评估移植的 MDSC 的数量和分化、肌纤维再生、I 型胶原形成和血管分布。在体外，MDSC 受到机械刺激，并对生长动力学进行量化。在体外，与对照组相比，机械刺激缩短了 MDSC 群体倍增时间（18.6 +/- 1.6 小时）和细胞分裂时间（10.9 +/- 0.7 小时）（群体倍增时间：23.0 +/- 3.4 小时；细胞分裂时间：13.3 +/- 1.1 小时）（分别为 p - 0.01 和 0.03）。在体内，与对照组相比，5周的TM增加了移植的MDSC的生肌作用（p - 0.02）。与 C + PBS 对照相比，C + MDSC、C + PBS + TM 和 C + MDSC + TM 在第 5 周时纤维化减少（分别为 p - 0.00、p - 0.03 和 p - 0.02）。结果表明，无论在体外还是体内，机械刺激都有利于 MDSC 增殖，并且运动可增强损伤后的 MDSC 移植。
Muscle-derived stem-cell (MDSC) transplantation presents a promising method for the treatment of muscle injuries. This study investigated the ability of exercise to enhance MDSC transplantation into the injured muscle. Mice were divided into four groups: contusion + phosphate-buffered saline (C + PBS; n = 14 muscles), C + MDSC transplantation (n = 12 muscles), C + PBS + treadmill running (C + PBS + TM; n = 17 muscles), and C + MDSC + TM (n 13 muscles). One day after injury, the TM groups began running for 1 or 5 weeks. Two days after injury, muscles of C + MDSC and C + MDSC + TM groups were injected with MDSCs. One or 5 weeks later, the number and differentiation of transplanted MDSCs, myofiber regeneration, collagen I formation, and vascularity were assessed histologically. In vitro, MDSCs were subjected to mechanical stimulation, and growth kinetics were quantified. In vitro, mechanical stimulation decreased the MDSC population doubling time (18.6 +/- 1.6 h) and cell division time (10.9 +/- 0.7 h), compared with the controls (population doubling time: 23.0 +/- 3.4 h; cell division time: 13.3 +/- 1.1 h) (p - 0.01 and 0.03, respectively). In vivo, 5 weeks of TM increased the myogenic contribution of transplanted MDSCs, compared with the controls (p - 0.02). C + MDSC, C + PBS + TM, and C + MDSC + TM demonstrated decreased fibrosis at 5 weeks, compared with the C + PBS controls (p - 0.00, p - 0.03, and p - 0.02, respectively). Results suggest that the mechanical stimulation favors MDSC proliferation, both in vitro and in vivo, and that exercise enhances MDSC transplantation after injury.