Stem Cell Homing Factor, CCL7, Expression in Mouse Models of Stress Urinary Incontinence

Abstract

Objectives Animal models of vaginal distention (VD) have demonstrated increased expression of chemokine (C-C motif) ligand 7 (CCL7). In this study, we investigated the expression of CCL7 in mice models of simulated birth trauma-induced urinary incontinence utilizing VD and pudendal nerve transection (PNT). Methods Forty-nine mice were divided into 6 groups: VD, sham VD, PNT, sham PNT anesthesia, and age-matched controls. The urethra, vagina, and rectum were harvested for the expression of CCL7 immediately or 24 hours after assigned procedure. Venous sampling for quantification of serum CCL7 was also performed. An ANOVA model was used to compare the relative expression of CCL7 in each group. Results Urethral CCL7 expression in the VD group was significantly higher than control group after 24 hours (p<0.01). There was no difference in the urethral CCL7 expression in PNT, sham PNT, sham VD or anesthesia groups compared with controls. No statistically significant difference was noted in the vaginal and rectal expression of CCL7 between any of the groups except for sham PNT. Statistically significant differences were noted in the serum CCL7 expression in VD, PNT and sham PNT (p<0.01 in all) groups after 24 hours compared with the control group. Conclusions This study demonstrates over-expression of urethral CCL7 after VD but not PNT. This suggests that nerve injury does not contribute to the CCL7 over-expression. The over-expression of CCL7 in the serum of mice after VD suggests a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery.

Electrical Stimulation Followed by Mesenchymal Stem Cells Improves Anal Sphincter Anatomy and Function in a Rat Model at a Time Remote From Injury

“…13 the cytokines involved include stromal cell-derived factor-1 (sDf-1, also known as CXCL12) 14 and monocyte chemo-attractant protein 3 (MCP-3, also known as CCL7). 15,16 CXCL12 and its receptor CXCR4 are crucial in regulating mesenchymal stem cell survival and differentiation. 17 in our preliminary studies, we have evaluated these cytokines in the anal sphincter and found that direct anal sphincter injury results in upregulation of CXCL12 and CCL7 expression soon after injury 18 and also after electrical stimulation.…”

Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse

“…These time points were selected based on the timecourse of cytokine expression in previous studies. 7,9,22,25,26 Loxl1 KO mouse gestation duration is approximately 21 days, so, as a feasible time point for studying the effects of pregnancy in the absence of delivery as a control for delivered mice, tissues were harvested on the 20 th day of gestation, prior to parturition for the pregnant group (Figure 1A). Sixty-four additional age-matched virgin Loxl1 KO female mice were utilized as sham cesarean injury controls or unmanipulated virgin controls (Figure 1A).…”

“…4–6 However, little research has been conducted to elucidate molecular markers for maternal injury in genitourinary tissues during the peripartum period that might provide insight into the mechanisms of injury that could lead to POP. 7–9 …”

“…7,9,20,21,25 Given the response of these cytokines to injury, they could be used as potential injury markers as they are mediators of inflammatory response. 8,18,23 We hypothesize that pregnancy and delivery mode will differentially affect the concentration and expression of CCL-7 and CXCL-12 both in the pelvic organs and systemically in Loxl1 KO and wildtype (WT) mice.…”

Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution

“…Cell therapy and tissue engineering are among the newest strategies under investigation for the treatment and prevention of SUI [4–6]. The therapeutic use of stem cell therapy in SUI is based on two broad approaches: (1) skeletal muscle regeneration using adult muscle-derived progenitor-cell therapy after injury, and (2) repair/prevention using stem cell therapy at the time of injury or initiation of the phenotype [7–9]. While the first approach relies on the ability of the stem cell to engraft and differentiate, the reparative approach depends on the paracrine and anti-inflammatory function of the stem cell.…”