The potential of extracellular microvesicles of mesenchymal stromal cells in obstetrics.

BACKGROUND: The rate of cesarean deliveries is steadily growing worldwide as a result of increasing maternal age at first delivery. Ensuring optimal recovery after surgery, specifically the development of a functionally competent uterine scar to facilitate vaginal birth after a cesarean delivery (VBAC), is one of the challenges in modern obstetrics. Extracellular microvesicles (EMVs) are secreted by multiple cell types and act as mediators of intercellular interaction during tissue reparation. The immunomodulatory and regenerative effects of EMVs of mesenchymal stromal cells (MSCs) have been studied shown in pre-clinical studies. AIM OF THE STUDY: To evaluate the safety profile of EMVs of mesenchymal stromal placental cells (MSPCs) injected during the cesarean delivery and the impact of this pilot approach on post-surgery recovery. MATERIALS AND METHODS: This pilot study included 53 women undergoing cesarean delivery with (n = 23) or without (n = 30) an injection of 500 µl of MSC EMVs after closing the uterine incision with a single continuous Vicryl suture. RESULTS: All study participants had uncomplicated post-surgery period. The mean inpatient stay duration in women receiving the EMV injection was 4.26 ± 0.09 days vs. 5.33 ± 0.38 in the control group (p<.05). There were no postpartum inflammatory complications in the study group compared with two cases (6.7%) by postpartum endometritis/myometrial infection and one case (3.3%) of lochiometra in the control group. SUMMARY: Intra-surgery injection of MSC EMVs was well-tolerated and associated with a lower rate of infectious post-partum complications in women undergoing cesarean delivery.

Angiogenesis in rat uterine cicatrix after injection of autologous bone marrow mesenchymal stem cells.

Results of injection of autologous bone marrow mesenchymal stem cells with transfected GFP gene into the rat uterine horn cicatrix were studied by light microscopy. Large groups of blood vessels with blood cells inside were seen after injection of autologous bone marrow cells into the cicatrix on the right horn, formed 2 months after its ligation; no groups of vessels of this kind were found in the cicatrix in the contralateral horn. Examination of unstained sections in reflected UV light showed sufficiently bright fluorescence in the endothelium and outer vascular membrane in the uterine horn cicatrix only on the side of injection. Hence, autologous mesenchymal stem cells injected into the cicatrix formed the blood vessels due to differentiation into endotheliocytes and pericytes. The expression of GFP gene not only in the vascular endothelium, but also in vascular outer membranes indicated that autologous mesenchymal stem cells differentiated in the endothelial and pericytic directions.

[Morphological analysis of the results of injection of the autologous stromal marrow-derived stem cells into the uterine scar in rats].

The results of injection of the autologous stromal (mesenchymal) marrow-derived stem cells (ASMSC) transfected with green fluorescent protein (GFP) gene into the rat uterine scar were studied by methods of light microscopy. One week after ASMSC injection into the formed scar on the right side (2 months after the uterine horn ligation), large groups of blood vessels containing the formed elements of blood were found, while these were absent in the uterine scar on the opposite side. The study of the unstained sections in the reflected ultraviolet light demonstrated bright luminescence in the vessel endothelium and adventitia in the uterine horn scar only at the side of ASMSC injection. It is suggested that after the injection of ASMSC in the uterine horn scar, they form blood vessels as result of a differentiation into endotheliocytes and pericytes. The expression of GFP gene not only in vascularl endothelium, but also in their adventitia, indicated that the differentiation ASMSC is possible in both endotheliocytes and in pericytes.