Effect of stem cell transplantation of premature ovarian failure in animal models and patients: A meta-analysis and case report

Abstract

Stem cell transplantation has been considered a promising therapeutic approach for premature ovarian failure (POF). However, to date, no quantitative data analysis of stem cell therapy for POF has been performed. Therefore, the present study performed a meta-analysis to assess the efficacy of stem cell transplantation in improving ovarian function in animal models of POF. In addition, a case report of a patient with POF subjected to stem cell treatment was included to demonstrate that stem cell therapy also contributes to the recovery of ovarian function in patients. Published studies were identified by a systematic review of the PubMed, Embase, and Cochrane's library databases, and references cited in associated reviews were also considered. Data regarding follicle-stimulating hormone (FSH), estradiol (E2), ovarian weight, follicle count, the number of pregnancies and other parameters, including delivery route and cell type, were extracted. Pooled analysis, sensitivity analyses, subgroup analyses and meta-regression were performed. In the case of POF, transvaginal ultrasound (TVS), abdominal ultrasound (TAS) and color Doppler flow imaging (CDFI) were performed to observe the endometrial morphology and blood flow signals in the patient. Overall, pooled results from 16 pre-clinical studies demonstrated that stem cell-based therapy significantly improved FSH levels [standardized mean difference (SMD)=−1.330; 95% confidence interval (CI), -(2.095–0.565); P=0.001], E2 levels (SMD=2.334; 95% CI, 1.350–3.319; P<0.001), ovarian weight (SMD=1.310; 95% CI, 0.157–2.463; P=0.026), follicle count (SMD=1.871; 95% CI, 1.226–2.516; P<0.001), and the number of pregnancies (risk ratio=1.715, 95% CI, 1.213–2.424; P=0.002). The results of TVS and TAS demonstrated improved ovarian size and endometrial thickness in the patient with POF after MSC treatment. Of note, a rich blood flow signal in the endometrium was observed on CDFI. It appeared that stem cell-based therapy may be an effective method for the resumption of ovarian function in a patient and in animal models of POF; however, large-scale and high-quality future studies are required to confirm the present findings due to heterogeneity.

Premature ovarian failure and tissue engineering

“…There are some curative methods for POF‐related infertility including HRT, egg donation, stem cell therapy, and tissue engineering (Burgos et al, ; Kawamura et al, ). As previously explained, a stem cell has also curative potentials in patients with POF that represents them as a novel method for clinical treatments (Chen et al, ). Stem cells can be derived from different sources; however, different types of stem cells are still hard to gain.…”

“…In MSCs transplantation, donor and receiver must have homogenous anatomical and physiological characteristics to reach an equal impact on therapeutic results (Sharma et al, ). There are several kinds of MSCs in regenerative medicine, such as umbilical cord mesenchymal stem cells (UCMSCs), ADSCs, ovarian granulosa‐like cells derived from human induced pluripotent stem cells (ovarian granulose cells [OGLCs]‐induced pluripotent stem cells [iPSCs]), human cord blood mononuclear cells, human endometrial MSCs, and BM‐MSCs (Chen et al, ). Among them, BM‐MSCs are brilliant candidates for regenerative medicine (Liu, Zhang et al, ).…”

“…Dormant viable oocytes can be also reestablished following MSCs‐based treatments (Isik et al, ). In a study, stem cell transplantation in a patient with POF resulted in an improved hormonal profile, menstruation renewal, pregnancy occurrence, and healthy term infant delivery (Chen et al, ). Chen et al () also reported that autologous MSCs transplantation in the POF animal model caused a significant increase in ovarian function.…”

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

“…POF, also called primary ovarian insufficiency, presents with amenorrhea, hypergonadotropism, and estrogen deficiency, followed by infertility, prior to the age of 40 years. It is estimated that POF affects 1% of all women worldwide [ 15 ]; however, its incidence has increased in recent years [ 16 ]. POF is a heterogeneous disorder due to its multicausal pathogenesis, involving genetic, infectious, enzymatic, and iatrogenic factors.…”

“…Some POF patients have idiopathic POF, with no identified etiology [ 17 ]. Available therapies for POF have low efficacy and may cause significant side effects, and there is a clear need for more comprehensive therapy to restore ovarian function in those with POF [ 16 ].…”