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

Publication ,  Journal Article
Kisby, CK; Shadrin, IY; Peng, LT; Stalboerger, PG; Trabuco, EC; Behfar, A; Occhino, JA
Published in: Female Pelvic Med Reconstr Surg
March 1, 2021

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.

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Published In

Female Pelvic Med Reconstr Surg

DOI

EISSN

2154-4212

Publication Date

March 1, 2021

Volume

27

Issue

3

Start / End Page

195 / 201

Location

United States

Related Subject Headings

  • Wound Healing
  • Vagina
  • Swine
  • Surgical Mesh
  • Suburethral Slings
  • Pelvic Organ Prolapse
  • Humans
  • Female
  • Exosomes
  • Animals
 

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Kisby, C. K., Shadrin, I. Y., Peng, L. T., Stalboerger, P. G., Trabuco, E. C., Behfar, A., & Occhino, J. A. (2021). Impact of Repeat Dosing and Mesh Exposure Chronicity on Exosome-Induced Vaginal Tissue Regeneration in a Porcine Mesh Exposure Model. Female Pelvic Med Reconstr Surg, 27(3), 195–201. https://doi.org/10.1097/SPV.0000000000001017
Kisby, Cassandra K., Ilya Y. Shadrin, Lillian T. Peng, Paul G. Stalboerger, Emanuel C. Trabuco, Atta Behfar, and John A. Occhino. “Impact of Repeat Dosing and Mesh Exposure Chronicity on Exosome-Induced Vaginal Tissue Regeneration in a Porcine Mesh Exposure Model.Female Pelvic Med Reconstr Surg 27, no. 3 (March 1, 2021): 195–201. https://doi.org/10.1097/SPV.0000000000001017.
Kisby CK, Shadrin IY, Peng LT, Stalboerger PG, Trabuco EC, Behfar A, et al. Impact of Repeat Dosing and Mesh Exposure Chronicity on Exosome-Induced Vaginal Tissue Regeneration in a Porcine Mesh Exposure Model. Female Pelvic Med Reconstr Surg. 2021 Mar 1;27(3):195–201.
Kisby, Cassandra K., et al. “Impact of Repeat Dosing and Mesh Exposure Chronicity on Exosome-Induced Vaginal Tissue Regeneration in a Porcine Mesh Exposure Model.Female Pelvic Med Reconstr Surg, vol. 27, no. 3, Mar. 2021, pp. 195–201. Pubmed, doi:10.1097/SPV.0000000000001017.
Kisby CK, Shadrin IY, Peng LT, Stalboerger PG, Trabuco EC, Behfar A, Occhino JA. Impact of Repeat Dosing and Mesh Exposure Chronicity on Exosome-Induced Vaginal Tissue Regeneration in a Porcine Mesh Exposure Model. Female Pelvic Med Reconstr Surg. 2021 Mar 1;27(3):195–201.

Published In

Female Pelvic Med Reconstr Surg

DOI

EISSN

2154-4212

Publication Date

March 1, 2021

Volume

27

Issue

3

Start / End Page

195 / 201

Location

United States

Related Subject Headings

  • Wound Healing
  • Vagina
  • Swine
  • Surgical Mesh
  • Suburethral Slings
  • Pelvic Organ Prolapse
  • Humans
  • Female
  • Exosomes
  • Animals