Impact of Repeat Dosing and Mesh Exposure Chronicity on Exosome-Induced Vaginal Tissue Regeneration in a Porcine Mesh Exposure Model

Cassandra K. Kisby, Ilya Y. Shadrin, Lillian T. Peng, Paul G. Stalboerger, Emanuel C. Trabuco, Atta Behfar, John A. Occhino

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: The aim of the study was to compare vaginal wound healing after exosome injection in a porcine mesh exposure model with (1) single versus multiple dose regimens and (2) acute versus subacute exposure. METHODS: Six 80-kg Yorkshire-crossed swine each had 2 polypropylene meshes implanted to create the vaginal mesh exposure model. Animals were divided into 3 groups based on number and timing of exosome injection: (1) single purified exosome product (PEP) injection (acute-single), (2) weekly PEP injections (acute-weekly, 4 total injections), and (3) delayed single injection (subacute-single). Acute and subacute injections occurred 1 and 8 weeks after mesh implantation, respectively. EdU, a thymidine analog, was given twice weekly after the first injection to track tissue regeneration. Euthanasia and tissue analysis occurred 4 weeks after the first injection. ImageJ was used to quantify epithelial thickness, cellular proliferation, and capillary density. Statistical analysis was performed using analysis of variance and post hoc Tukey test. RESULTS: Acute-single PEP injection tissues mirrored pilot study results, validating replication of protocol. Within the acute groups, weekly dosing resulted in 1.5× higher epithelial thickness (nonsignificant), 1.8× higher epithelial proliferation (P < 0.05), and 1.5× higher regenerated capillary density (P < 0.05) compared with single injection. Regarding chronicity of the exposure, the subacute group showed 1.7× higher epithelial proliferation (nonsignificant) and similar capillary density and epithelial thickness as compared with the acute group. CONCLUSIONS: Exosome redosing resulted in significantly greater epithelial proliferation with significantly higher regenerated capillary density, leading to a trend toward thicker epithelium. Subacute exposure exhibited similar regeneration to acute exposure despite a delayed injection timeline. These results contribute to a growing body of preclinical research demonstrating utility of exosomes in pelvic floor disorders.

Original languageEnglish (US)
Pages (from-to)195-201
Number of pages7
JournalFemale Pelvic Medicine and Reconstructive Surgery
Volume27
Issue number3
DOIs
StatePublished - Mar 1 2021

ASJC Scopus subject areas

  • Surgery
  • Obstetrics and Gynecology
  • Urology

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