Bone Marrow-Derived Stem Cell (BMDSC) Transplantation Improves Fertility in a Murine Model of Asherman's Syndrome

Abstract

Asherman's Syndrome is characterized by intrauterine adhesions or fibrosis resulting as a consequence of damage to the basal layer of endometrium and is associated with infertility due to loss of normal endometrium. We have previously shown that bone marrow derived stem cells (BMDSCs) engraft the endometrium in mice and humans and Ischemia/reperfusion injury of uterus promoted BMDSCs migration to the endometrium; however, the role of BMDSCs in Asherman's syndrome has not been characterized. Here a murine model of Asherman's syndrome was created by traumatizing the uterus. We evaluate stem cell recruitment and pregnancy after BMDSCs transplantation in a model of Asherman's syndrome. In the Asheman's syndrome model, after BMDSC transplant, the Y chromosome bearing CD45-cells represented less than 0.1% of total endometrial cells. Twice the number of Y+CD45- cells was identified in the damaged uterus compared to the uninjured controls. There was no significant difference between the damaged and undamaged uterine horns in mice that received injury to a single horn. In the BMDSC transplant group, 9 of the 10 mice conceived, while only 3 of 10 in the non-transplanted group conceived (Chi-Square p = 0.0225); all mice in an uninjured control group conceived. The time to conception and mean litter size were not different between groups. Taken together, BMDSCs are recruited to endometrium in response to injury. Fertility improves after BMDSC transplant in Asherman's Syndrome mice, demonstrating a functional role for these cells in uterine repair. BMDSC transplantation is a potential novel treatment for Asherman's Syndrome and may also be useful to prevent Asherman's syndrome after uterine injury.

Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways

“…However, there was no significant difference in the endometrial thickness between two groups 14 days after grafting, which indicated that MenSCs indeed have the potential to accelerate the restoration and regeneration of the damaged endometrium in agreement with Jing's study (Jing et al 2014). Our study also showed higher pregnancy rate and more fetal numbers in injured horn of MenSCs-treated mice than that of control group, which was similar to the BMSCs transplantation trial reported by Alawadhi and coworkers 2 years ago (Alawadhi et al 2014). Above all, our data suggested that treatment with MenSCs could promote endometrial restoration and improve mice fertility after uterine injury.…”

“…Another study presented that autologous stem cell transplantation led to endometrial regeneration reflected by restoration of menstruation in five out of six patients with refractory Asherman's syndrome (Singh et al 2014). Lately, several animal studies have demonstrated that MSCs could repair the injured endometrium, but the repair mechanisms of MSCs were not investigated (Alawadhi et al 2014, Jing et al 2014, Kilic et al 2014. Based on these studies, here we established a mouse endometrial injury model by electrocoagulation to evaluate the therapeutic effects of stem cells, which was more easily performed than the mechanical methods described by Alawadhi and coworkers (2014), (Hu et al 2014).…”

“…It has been proposed that condition medium from MSCs was effective for reducing myocardial ischemia (Jiang et al 2013), improving limb reperfusion (Kinnaird et al 2004b, Kwon et al 2014 and protecting against acute kidney injury (Togel et al 2007, Camussi et al 2010. Recently, several studies have reported that bone marrow stem cells (BMSCs) could induce the regeneration of thin endometrium and injured endometrium in animal experiments (Alawadhi et al 2014, Jing et al 2014, Kilic et al 2014. However, the potential function and the underlying molecular mechanism of MSCs in IUAs repair yet need to be uncovered.…”

Transplant of insulin‐like growth factor‐1 expressing bone marrow stem cells improves functional regeneration of injured rat uterus by NF‐κB pathway

“…Our previous study demonstrated promising therapeutic effect of minimally invasive BMSCs transplantation in the uterine prolapse rat model 6. Likewise, another investigation showed that BMSCs differentiated into endometrial epithelial cells, which promoted proliferation of endometrial stromal cells and accretion of endometrium, and eventually contributed to the elevated pregnancy rate in the endometrial damage animal model 7. More importantly, Singh et al proposed the autologous stem cell transplantation as a novel cell‐based therapy for refractory Asherman's syndrome 8.…”

The endometrium as a source of mesenchymal stem cells in domestic animals and possible applications in veterinary medicine

“…73,75 Furthermore, BMDSC transplantation in a murine model of Asherman's syndrome improved fertility in the mice, demonstrating a functional role for these cells in uterine repair. 76 Many reproductive alterations are associated with abnormal endometrial proliferation; therefore, endometrial MSCs may perform an important role in the physiopathology of diseases, including human endometriosis, adenomyosis, and infertility problems related to hypoplasia or endometrial atrophy, 53 and probably in some important diseases within veterinary medicine, such as cystic endometrial hyperplasia in dogs, equine endometriosis and endometrial cancer. However, these roles have…”