Therapeutic Effects of VEGF Gene-Transfected BMSCs Transplantation on Thin Endometrium in the Rat Model

Abstract

Objective Bone mesenchymal stem cells (BMSCs) transplantation has a therapeutic effect on the thin endometrium in animal researches and clinical trials. The present study aims at assessing whether transplantation of VEGF-transfected BMSCs (VEGF-BMSCs) have a better therapeutic effect on endometrial regeneration and endometrial receptivity compared with BMSCs therapy alone. Methods Sprague-Dawley (SD) rats were used in the study. Thin endometrium model was established with 95% ethanol injection into uterine. VEGF-BMSCs or BMSCs was transplanted via tail vein IV injection. Endometrial thickness, morphology, and pinopodes were assessed by hematoxylin and eosin (HE) staining and scanning electron microscope (SEM). The proteins and mRNAs expressions of markers for endometrial cells and endometrial receptivity were measured after treatment. The fertility testing was done to assess the embryo implantation efficiency. Results VEGF-BMSCs transplantation significantly increased endometrial thickness compared with the BMSCs group and the control group. There was no significant difference in endometrial thickness between VEGF-BMSCs group and sham operation group. Importantly, in protein level, expressions of cytokeratin, vitamin, VEGF, LIF, and integrin ανβ 3 in VEGF-BMSC group were increased dramatically compared with those of the control group and BMSC group both 4 days and 8 days after stem cells transplantation. Accordingly, mRNA expression of LIF and integrin α ν β 3 was significantly upregulated compared with those of the control group and BMSC group both 4 and 8 days after treatment. The pinopodes were developed better in the VEGF-BMSCs group and the sham operation group compared with BMSCs group and the control group. The number of embryo implantation is largest in the sham operation group, followed by VEGF-BMSCs group, BMSCs group, and the control group. Conclusions Transplantation of VEGF gene-transfected BMSCs may be a better therapeutic treatment for thin endometrium than stem cell therapy alone.

The synergistic effect of electroacupuncture and bone mesenchymal stem cell transplantation on repairing thin endometrial injury in rats

“…A clinical investigation has proved that stem cells existing in the endometrium may originate from the bone marrow [43]. A number of experiments have demonstrated that BMSCs appeared to play an important role in endometrial rebuilding [10, 44–49].…”

“…There are several methods to enhance the effect of MSCs on injury repair: The first method is to combine collagen scaffolds or other biological materials and transplant them directly to the site of injury [51]. The second method is to utilize growth factors, such as heparin-binding epidermal growth factor and VEGF [44, 52]. The third method is to genetically modify MSCs [53].…”

Encapsulated VEGF121-PLA microparticles promote angiogenesis in human endometrium stromal cells

“…However, several studies are stating that vascularization of the endometrium is regulated by VEGF [ 20 – 23 ]. In a study conducted by Jing et al [ 23 ], VEGF transfected with bone marrow-derived stromal cells (BMSCs) in a rat model showed that rats injected with VEGF-transfected BMSCs had thicker endometrium than the control group and BMSC group [ 23 ]. This method of transplantation also promoted the regeneration of endometrial cells and proven to be a stronger therapeutic effect.…”

Stem Cell-Based Therapy for Asherman Syndrome: Promises and Challenges

“…The VEGF gene transfected BMDSC transplantation is supposed to promote the regeneration of endometrium and improve the endometrial receptivity. The combination revealed a better therapeutic effect than BMDSC treatment alone 63 . BMDSCs show greater ability to migrate to the uterus by systemic injections than EnSCs, resulting in a higher proportion of in situ donor cells 64 .…”