Proregenerative extracellular matrix hydrogel mitigates pathological alterations of pelvic skeletal muscles after birth injury.

Autor: Duran P; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA., Boscolo Sesillo F; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA.; Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Female Pelvic Medicine and Reconstructive Surgery, University of California San Diego, La Jolla, CA 92093, USA., Cook M; Department of Integrative, Biology and Physiology, University of Minnesota, Minneapolis, MN 55455, USA., Burnett L; Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Female Pelvic Medicine and Reconstructive Surgery, University of California San Diego, La Jolla, CA 92093, USA., Menefee SA; Department of Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, Kaiser Permanente, San Diego, CA 92110, USA., Do E; Department of Biology, University of California San Diego, La Jolla, CA 92093, USA., French S; Department of Biology, University of California San Diego, La Jolla, CA 92093, USA., Zazueta-Damian G; Department of Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, Kaiser Permanente, San Diego, CA 92110, USA., Dzieciatkowska M; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, CO 80045, USA., Saviola AJ; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, CO 80045, USA., Shah MM; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA., Sanvictores C; Department of Physics, University of California San Diego, La Jolla, CA 92093, USA., Osborn KG; Center for Veterinary Sciences and Comparative Medicine, Division of Comparative Pathology and Medicine, University of California San Diego, La Jolla, CA 92093, USA., Hansen KC; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, CO 80045, USA., Shtrahman M; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA.; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA., Christman KL; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA., Alperin M; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA.; Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Female Pelvic Medicine and Reconstructive Surgery, University of California San Diego, La Jolla, CA 92093, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2023 Aug 02; Vol. 15 (707), pp. eabj3138. Date of Electronic Publication: 2023 Aug 02.
DOI: 10.1126/scitranslmed.abj3138
Abstrakt: Pelvic floor disorders, including pelvic organ prolapse and urinary and fecal incontinence, affect millions of women globally and represent a major public health concern. Pelvic floor muscle (PFM) dysfunction has been identified as one of the leading risk factors for the development of these morbid conditions. Childbirth, specifically vaginal delivery, has been recognized as the most important potentially modifiable risk factor for PFM injury; however, the precise mechanisms of PFM dysfunction after parturition remain elusive. In this study, we demonstrated that PFMs exhibit atrophy and fibrosis in parous women with symptomatic pelvic organ prolapse. These pathological alterations were recapitulated in a preclinical rat model of simulated birth injury (SBI). The transcriptional signature of PFMs after injury demonstrated an impairment in muscle anabolism, persistent expression of genes that promote extracellular matrix (ECM) deposition, and a sustained inflammatory response. We also evaluated the administration of acellular injectable skeletal muscle ECM hydrogel for the prevention of these pathological alterations. Treatment of PFMs with the ECM hydrogel either at the time of birth injury or 4 weeks after injury mitigated PFM atrophy and fibrosis. By evaluating gene expression, we demonstrated that these changes are mainly driven by the hydrogel-induced enhancement of endogenous myogenesis, ECM remodeling, and modulation of the immune response. This work furthers our understanding of PFM birth injury and demonstrates proof of concept for future investigations of proregenerative biomaterial approaches for the treatment of injured pelvic soft tissues.
Databáze: MEDLINE