Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury
Abstract 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 app...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-12-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-022-00264-1 |
| _version_ | 1828089984747307008 |
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| author | Francesca Boscolo Sesillo Varsha Rajesh Michelle Wong Pamela Duran John B. Rudell Courtney P. Rundio Brittni B. Baynes Louise C. Laurent Alessandra Sacco Karen L. Christman Marianna Alperin |
| author_facet | Francesca Boscolo Sesillo Varsha Rajesh Michelle Wong Pamela Duran John B. Rudell Courtney P. Rundio Brittni B. Baynes Louise C. Laurent Alessandra Sacco Karen L. Christman Marianna Alperin |
| author_sort | Francesca Boscolo Sesillo |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T05:49:55Z |
| format | Article |
| id | doaj.art-86125534191e496297718193c6076989 |
| institution | Directory Open Access Journal |
| issn | 2057-3995 |
| language | English |
| last_indexed | 2024-04-11T05:49:55Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj.art-86125534191e496297718193c60769892022-12-22T04:42:05ZengNature Portfolionpj Regenerative Medicine2057-39952022-12-017111210.1038/s41536-022-00264-1Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injuryFrancesca Boscolo Sesillo0Varsha Rajesh1Michelle Wong2Pamela Duran3John B. Rudell4Courtney P. Rundio5Brittni B. Baynes6Louise C. Laurent7Alessandra Sacco8Karen L. Christman9Marianna Alperin10Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Female Pelvic Medicine and Reconstructive Surgery, University of California, San DiegoDivision of Biological Sciences, University of California, San DiegoDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Division of Female Pelvic Medicine and Reconstructive Surgery, University of California, San DiegoSanford Consortium for Regenerative MedicineDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Division of Female Pelvic Medicine and Reconstructive Surgery, University of California, San DiegoDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Division of Female Pelvic Medicine and Reconstructive Surgery, University of California, San DiegoDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Division of Female Pelvic Medicine and Reconstructive Surgery, University of California, San DiegoSanford Consortium for Regenerative MedicineDevelopment, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery InstituteSanford Consortium for Regenerative MedicineDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Division of Female Pelvic Medicine and Reconstructive Surgery, University of California, San DiegoAbstract 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.https://doi.org/10.1038/s41536-022-00264-1 |
| spellingShingle | Francesca Boscolo Sesillo Varsha Rajesh Michelle Wong Pamela Duran John B. Rudell Courtney P. Rundio Brittni B. Baynes Louise C. Laurent Alessandra Sacco Karen L. Christman Marianna Alperin Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury npj Regenerative Medicine |
| title | Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury |
| title_full | Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury |
| title_fullStr | Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury |
| title_full_unstemmed | Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury |
| title_short | Muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury |
| title_sort | muscle stem cells and fibro adipogenic progenitors in female pelvic floor muscle regeneration following birth injury |
| url | https://doi.org/10.1038/s41536-022-00264-1 |
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