Mesenchymal Stem Cell Therapy Following Muscle Trauma Leads to Improved Muscular Regeneration in Both Male and Female Rats

Philipp von Roth MD , Georg N. Duda PhD , Piotr Radojewski , Bernd Preininger MD , Carsten Perka MD , Tobias Winkler MD, PhD
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引用次数: 27

Abstract

Background

Mesenchymal stem cell (MSC) therapy has the potential to enhance muscular regeneration. In previous publications, our group was able to show a dose-response relationship in female animals between the amount of transplanted cells and muscle force. The impact of sex on the regeneration of musculoskeletal injuries following MSC transplantation remains unclear.

Objective

We investigated histologic and biomechanical regeneration parameters in rats after autologous transplantation of MSCs. Our hypothesis was that female rats have greater muscle regeneration potential than male rats after autologous MSC transplantation.

Methods

Thirty-six Sprague-Dawley rats received an open crush trauma of the left soleus muscle. One week after trauma, 2.5 × 106 autologous MSCs, harvested from tibial biopsies, were transplanted locally (female, n = 9; male, n = 9). Control animals received saline solution (female, n = 9; male, n = 9). Histologic analysis and biomechanical evaluation by in vivo muscle force measurement were performed 3 weeks after transplantation.

Results

MSC therapy improved the force of the injured soleus in male rats significantly (twitch: treated, 0.76 [0.51–1.15]; twitch: untreated, 0.45 [0.32–0.73] [P = 0.01]; tetany: treated, 0.63 [0.4–1.21], tetany: untreated, 0.34 [0.16–0.48] [P = 0.04]). Force measurements in females also revealed significant improvements (twitch: treated, 0.71 [0.38–0.96]; twitch: untreated, 0.36 [0.18–0.63] [P = 0.005]; tetany: treated, 0.53 [0.21–0.68]; tetany: untreated, 0.27 [0.11–0.47] [P = 0.01]). The intersexual comparison of fast twitch and tetanic contraction forces revealed no significance (twitch, P = 0.55; tetany, P = 0.19). The histologic analysis showed no differences in the amount of fibrotic tissue (male, P = 0.9; female, P = 0.14) and the size of muscle area (male, P = 0.2; female, P = 0.56) following treatment. Male animals showed higher values for muscle area (P = 0.011) and less fibrosis (P = 0.028), independent of treatment.

Conclusion

The outcome of skeletal muscle regeneration after injury can be improved in animals of both sexes with MSC transplantation.

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肌肉创伤后间充质干细胞治疗可改善雌雄大鼠的肌肉再生
间充质干细胞(MSC)治疗具有增强肌肉再生的潜力。在之前的出版物中,我们的小组能够在雌性动物中展示移植细胞数量和肌肉力量之间的剂量-反应关系。性别对间充质干细胞移植后肌肉骨骼损伤再生的影响尚不清楚。目的研究大鼠自体骨髓间充质干细胞移植后的组织学和生物力学参数。我们的假设是雌性大鼠在自体间充质干细胞移植后比雄性大鼠具有更大的肌肉再生潜力。方法36只Sprague-Dawley大鼠采用左比目鱼肌开放性挤压伤。创伤后1周,从胫骨活检中获取2.5 × 106个自体MSCs,局部移植(女性,n = 9;雄性,n = 9)。对照动物接受生理盐水(雌性,n = 9;男性,n = 9)。移植后3周进行组织学分析并通过体内肌肉力测量进行生物力学评价。结果smsc治疗可显著改善雄性大鼠损伤比目鱼肌的受力(抽搐:治疗,0.76 [0.51-1.15];抽搐:未治疗,0.45 [0.32-0.73][P = 0.01];手足搐搦:治疗组,0.63[0.4 ~ 1.21];手足搐搦:未治疗组,0.34 [0.16 ~ 0.48][P = 0.04])。女性的力量测量也显示出显著的改善(抽搐:治疗,0.71 [0.38-0.96];抽搐:未治疗,0.36 [0.18-0.63][P = 0.005];手足搐搦症:治疗组,0.53 [0.21-0.68];手足搐搦症:未治疗,0.27 [0.11-0.47][P = 0.01])。两性间快速抽动与强直收缩力比较无显著性差异(抽动,P = 0.55;tetany, P = 0.19)。组织学分析显示,两组间纤维化组织数量无差异(男性,P = 0.9;女性,P = 0.14)和肌肉面积大小(男性,P = 0.2;女性,P = 0.56)。雄性动物的肌肉面积较高(P = 0.011),纤维化较少(P = 0.028),与治疗无关。结论骨髓间充质干细胞移植可改善骨骼肌损伤后的再生效果。
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Gender Medicine
Gender Medicine 医学-医学:内科
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