An Autologous Cell Based Tissue Engineered Therapy for Vaginal Birth Injury : a Virgin Ovine Model Study

Mukherjee S1, Darzi S1, Rosamilia A2, Karjalainen P2, Paul K1, Werkmeister J1, Gargett C1

Research Type

Pure and Applied Science / Translational

Abstract Category

Pelvic Organ Prolapse

Abstract 471
Open Discussion ePosters
Scientific Open Discussion Session 30
Saturday 10th September 2022
11:20 - 11:25 (ePoster Station 3)
Exhibition Hall
Stem Cells / Tissue Engineering Pre-Clinical testing Pelvic Organ Prolapse Basic Science Cell Culture
1. Hudson Institute of Medical Research and Monash University, 2. Monash Health and Monash University
Not Presented
Presenter
Links

Abstract

Hypothesis / aims of study
Vaginal childbirth causes significant pelvic floor trauma in women. Maternal childbirth injury is the leading risk factor for pelvic floor muscle disorders (PFDs) including urinary incontinence (UI) and Pelvic Organ Prolapse (POP). Although the damage occurs during childbirth, its impact is often seen much later in life when women start developing symptoms of POP such as a vaginal bulge or a dragging sensation, and bladder, bowel, and sexual dysfunction that impacts 1 in 4 women across all ages. At present, there is no optimal therapy or surgical intervention for POP treatment given the high failure rates of native tissue repair. Even after 12 years, PFDs such as UI persists in 75% of women as a result of vaginal delivery, highlighting the need for newer strategies for combating PFDs. The development of new therapies for maternal birth injuries are largely limited due to the lack of a suitable large animal model that mimics human birth. Rather than wait for the majority of women to develop POP at menopause, we propose to develop a prophylactic therapy for POP to be injected soon after childbirth by delivering mesenchymal stem cells from their endometrium in a novel nanogel.
Study design, materials and methods
Herein, we selected virgin sheep and simulated birth injury using a water balloon catheter that is clinically used to mitigate post-partum uterine bleeding. Autologous endometrial Mesenchymal stem cells (eMSCs) were obtained from uterine biopsies from sheep following a hysterectomy.  The cells were purified to CD271+ and CD49f-  and cultured on short degradable polymeric nanofibers suspended in gelatin gel (NanoGel) and transplanted after 30 days of simulated vaginal birth injury. Sheep transplanted with nanogel without eMSCs and sham injury served as control. After another 30days of observation, vaginal laxity was measured and whole vaginas were explanted and histologically assessed using electron microscopy, histology stains and immunohistochemistry.
Results
We observed that birth injury in virgin sheep is characterised by disruption of collagen, smooth muscle cells and elastin content within the vaginal tissue. However, an injection of eMSC nanogel treatment after simulated injury could reverse these alternations. Furthermore, eMSC based therapy promoted angiogenesis as some cells were retained up to 30 days without triggering unwanted foreign body response.
Interpretation of results
With the rising ageing population, POP represents a significant concern and healthcare burden due to the lack of an optimal long-term solution. In this study, we report the first ovine model of birth injury and explore the possibility of repairing vaginal damage soon after birth injury, as a strategy to promote early healing to prevent progression to POP.
Concluding message
This study further assessed a simple autologous tissue engineered biosystem to repair and reverse childbirth induced vaginal injuries, thus providing a major women’s health problem of society.
Disclosures
Funding This work was financially supported by an International Postgraduate Research Training and Monash Graduate Scholarships (K.P.); CASS Foundation (Grant No. 7849); Science and Industry Endowment Fund (Grant no. PF16-122); CSIRO Clayton Australia; National Health and Medical Research Council (NHMRC) of Australia (Grant Nos.1184841 (SM, JW), 1173882 (CG) and 1159677 (CG, SM, JW) and the Victorian Government's Operational Infrastructure Support Program. Clinical Trial No Subjects Animal Species sheep Ethics Committee Monash Medical Centre Committee A
13/11/2024 21:26:54