Center for Musculoskeletal Surgery and Julius Wolff Institute, Berlin Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
J Tissue Eng Regen Med. 2012 Dec;6 Suppl 3:s60-7. doi: 10.1002/term.1542. Epub 2012 Jul 4.
Mesenchymal stem cell (MSC) therapy is a promising approach for regaining muscle function after trauma. Prior to clinical application, the ideal time of transplantation has to be determined. We investigated the effects of immediate and delayed transplantation. Sprague-Dawley rats received a crush trauma to the left soleus muscle. Treatment groups were transplanted locally with 2 × 10(6) autologous MSCs, either immediately or 7 days after trauma. Saline was used as sham therapy. Contraction force tests and histological analyses were performed 4 weeks after injury. GFP-labelled MSCs were followed after transplantation. The traumatized soleus muscles of the sham group displayed a reduction of twitch forces to 36 ± 17% and of tetanic forces to 29 ± 11% of the non-injured right control side, respectively. Delayed MSC transplantation resulted in a significant improvement of contraction maxima in both stimulation modes (twitch, p = 0.011; tetany, p = 0.014). Immediate transplantation showed a significant increase in twitch forces to 59 ± 17% (p = 0.043). There was no significant difference in contraction forces between muscles treated by immediate and delayed cell transplantation. We were able to identify MSCs in the interstitium of the injured muscles up to 4 weeks after transplantation. Despite the fundamental differences of the local environment, which MSCs encounter after transplantation, similar results could be obtained with respect to functional muscle regeneration. We believe that transplanted MSCs residing in the interstitial compartment evolve their regenerative capabilities through paracrine pathways. Our data suggest a large time window of the therapeutical measures.
间充质干细胞（MSC）治疗是一种有前途的方法，可在创伤后恢复肌肉功能。在临床应用之前，必须确定理想的移植时间。我们研究了即刻和延迟移植的效果。Sprague-Dawley 大鼠的左比目鱼肌受到挤压伤。治疗组通过局部移植 2×10（6）个自体 MSC，分别在创伤后即刻或 7 天进行移植。生理盐水用作假治疗。在损伤后 4 周进行收缩力测试和组织学分析。移植后追踪 GFP 标记的 MSC。假治疗组的受伤比目鱼肌的单次收缩力分别降至非受伤右侧对照侧的 36±17%和强直收缩力的 29±11%。延迟 MSC 移植可显著改善两种刺激模式下的收缩最大值（单次收缩，p=0.011；强直收缩，p=0.014）。即刻移植可使单次收缩力显著增加至 59±17%（p=0.043）。即刻和延迟细胞移植治疗的肌肉收缩力之间无显著差异。我们能够在移植后 4 周内在受伤肌肉的间质中识别 MSC。尽管移植后 MSC 所处的局部环境存在根本差异，但在功能肌肉再生方面仍可获得相似的结果。我们认为，驻留在间质隔室中的移植 MSC 通过旁分泌途径发展其再生能力。我们的数据表明治疗措施有很大的时间窗口。
