Login to Access Video or Poster Abstract: MP41-08
Sources of Funding: The First Affiliated Hospital of Wenzhou Medical University, NSF China 81670695, and China America Promotion Society for Medical Doctors (CAPs MD)

Introduction

Birth trauma is a widely recognized risk factor in the genesis of stress urinary incontinence (SUI) in women. Cell-based therapies for SUI have shown promising results. However, the treatment effects of mesenchymal stem cells (MSCs) transplantation are limited due to poor survival and engraftment in the injured tissues. Previous studies have shown that chemokine (C-C motif) ligand 7 (CCL7) production is increased significantly at the injured tissues around pelvic outlet after simulated birth injury. CCL7 enhances MSCs homing through interactions with its receptor, particularly C-C motif receptor 1(CCR1), on MSCs. We aim to determine if overexpression of CCR1 in MSCs and treatment with CCL7 can improve MSCs survival, migration, and engraftment after simulated birth injury.

Methods

Sprague Dawley rat MSCs were retrovirally transfected with enhanced green fluorescent protein (eGFP) or CCR1-eGFP. GFP expression in MSCs was evaluated and GFP-positive MSCs were sorted using flow cytometry. Migration and survival of CCR1-overexpressing MSCs stimulated by CCL7 were tested in vitro. In vivo, MSCs were intravenously administrated, and CCL7 or saline was injected suburethrally after simulated birth injury, vaginal distension. The injured tissues around pelvic outlet, including urethra and vagina, were harvested for analysis of MSCs homing 1 days or 1 week after simulated birth injury.

Results

In vitro, CCL7 stimulation increased migration of CCR1-overexpressing MSCs significantly (p<0.01), and protected CCR1-MSCs from apoptosis 12 hours after serum withdrawal (p<0.05). Quantitative analysis of MSCs in injured tissues around pelvic outlet demonstrated intravenous administration of CCR1-overexpressing MSCs and suburethral injection of CCL7 increased MSCs homing significantly both 1 day and 1 week after simulated birth injury (p<0.05).

Conclusions

Treatment of CCR1-overexpressing MSCs with CCL7 enhances their migration and survival in vitro. Intravenous administration of CCR1-overexpressing MSCs combined with suburethral injection of CCL7 increased MSCs engraftment, and may be a new therapeutic strategy for birth trauma-related SUI. _x000D_

Funding

The First Affiliated Hospital of Wenzhou Medical University, NSF China 81670695, and China America Promotion Society for Medical Doctors (CAPs MD)