Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury.
Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury.
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DOI：
10.1038/s41536-022-00264-1
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发表时间：
2022-12-16
影响因子：
7.2
通讯作者：
Alperin M
中科院分区：
文献类型：
--
作者：
Sesillo FB;Rajesh V;Wong M;Duran P;Rudell JB;Rundio CP;Baynes BB;Laurent LC;Sacco A;Christman KL;Alperin M
分娩期间盆底肌肉 (PFM) 损伤是盆底疾病的一个关键风险因素，影响着全球数百万女性。肌肉干细胞 (MuSC) 在纤维脂肪祖细胞 (FAP) 和免疫细胞的支持下，对于受损阑尾骨骼肌的再生至关重要。然而，人们对它们在产伤后 PFM 再生中的作用几乎一无所知。为了阐明 MuSC、FAP 和免疫浸润在这种情况下的作用，我们使用辐射扰乱细胞功能，并在经过验证的模拟产伤 (SBI) 大鼠模型中跟踪 PFM 恢复。在 SBI (dpi) 后 3、7、10 和 28 天对未照射和照射的大鼠实施安乐死。 28 dpi 时，相对于未受辐射的受伤动物，受辐射的 PFM 纤维横截面积 (CSA) 显着较低，免疫浸润占据的细胞外空间更大。在未受辐射的动物中进行 SBI 后，MuSC 和 FAP 分别在 7 dpi 和 3 dpi 时显着扩增；这种扩张并未在同一时间点的受辐射动物中发生。在 7 和 10 dpi 时，我们观察到与未受辐射损伤的 PFM 相比，受辐射的 PFM 具有持续的免疫反应。与未受辐照的损伤 PFM 相比，受辐照的 SBI 后新再生纤维的 CSA 也显着较小。我们的结果表明，产伤后 MuSC 和 FAP 的功能丧失和扩张减少导致 PFM 恢复受损。这些发现为进一步研究奠定了基础，重点是确定新的治疗靶点，以对抗产后 PFM 功能障碍和相关的盆底疾病。
Pelvic floor muscle (PFM) injury during childbirth is a key risk factor for pelvic floor disorders that affect millions of women worldwide. Muscle stem cells (MuSCs), supported by the fibro-adipogenic progenitors (FAPs) and immune cells, are indispensable for the regeneration of injured appendicular skeletal muscles. However, almost nothing is known about their role in PFM regeneration following birth injury. To elucidate the role of MuSCs, FAPs, and immune infiltrate in this context, we used radiation to perturb cell function and followed PFM recovery in a validated simulated birth injury (SBI) rat model. Non-irradiated and irradiated rats were euthanized at 3,7,10, and 28 days post-SBI (dpi). Twenty-eight dpi, PFM fiber cross-sectional area (CSA) was significantly lower and the extracellular space occupied by immune infiltrate was larger in irradiated relative to nonirradiated injured animals. Following SBI in non-irradiated animals, MuSCs and FAPs expanded significantly at 7 and 3 dpi, respectively; this expansion did not occur in irradiated animals at the same time points. At 7 and 10 dpi, we observed persistent immune response in PFMs subjected to irradiation compared to non-irradiated injured PFMs. CSA of newly regenerated fibers was also significantly smaller following SBI in irradiated compared to non-irradiated injured PFMs. Our results demonstrate that the loss of function and decreased expansion of MuSCs and FAPs after birth injury lead to impaired PFM recovery. These findings form the basis for further studies focused on the identification of novel therapeutic targets to counteract postpartum PFM dysfunction and the associated pelvic floor disorders.
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影响因子：
4.6
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Lepper, Christoph;Partridge, Terence A.;Fan, Chen-Ming
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Fan, Chen-Ming
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Dumont, Nicolas A.;Bentzinger, C. Florian;Rudnicki, Michael A.
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