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.

Sonoelastography for the comparative assessment of cervical maturation after different approaches to cervical preparation ahead of labor induction.

AIM: To compare the efficacy of different approaches to cervical preparation to labor induction using the ultrasound cervical elastography. MATERIALS AND METHODS: This prospective open-label study included 200 pregnant women aged between 23 and 38 years eligible for labor pre-induction. Patients were divided into four groups (n = 50 per group). In Group I, four osmotic Dilapan-S cervical dilators combined with two doses of oral mifepristone (200 mg each) 24 h apart were used. The dilators were inserted for up to 12 h. In Group II, only the Dipalan-S dilators were used. In Group III, a Foley catheter was positioned intracervically for 12 h. In Group IV, we used two doses of intracervical prostaglandin E2 gel (0.5 mg each) 6 h apart. Cervical maturation was assessed using the Bishop scoring system and the ultrasound cervicometry with the color mapping and calculation of SR ratio. At baseline, all participants were also divided into three subgroups depending on the Bishop score before the pre-induction. Subgroup А (n = 66) included patients with the Bishop score between 0‒2 points, subgroup B (n = 69) between 3-4 points, and subgroup С (n = 65) between 4-6 points. RESULTS: Our study showed that the efficacy of Dilapan-S combined with mifepristone for cervical preparation to labor induction was higher than Dilapan-S, Foley catheter and intracervical prostaglandin E2 gel. In this group, the Bishop score after the pre-induction was the highest (11.4 (0.21) points versus 10.2 (0.2), 9.4 (0.3) и 9.67 (0.25) in Groups II, III and IV respectively (p < .05 for all). The lowest SR values were also observed among the patients receiving the combination of Dilapan-S and mifepristone: 1.23 (0.04) versus 1.63 (0.07), 1.7 (0.08) and 1.83 (0.1) in Groups II, III and IV respectively (p < .05 for all). The sonoelastographic SR values in subgroups B and C were statistically lower compared with subgroup A across all groups studied. Ultrasound elastography of the cervix allowed to perform a more objective assessment of cervical maturation compared with the Bishop scoring. CONCLUSION: Dilapan-S combined with mifepristone had higher efficacy for cervical preparation to labor induction compared with other approaches investigated.

[THE PECULIARITIES OF UTERINE STRUCTURE AFTER DELIVERY IN RATS WITH THE MYOMETRIAL SCAR].

The uterine tissues of female rats (n=30) with a scarred myometrium were examined by methods of light microscopy after the delivery. 1.5-2 months after the delivery no significant differences in the parameters of blood and lymph flow in the deep layers of the endometrium, myometrium and the myometrial scar tissue were found between the intact rats, nulliparous rats with a scarred uterus, rats that gave birth after laparotomy only and those that gave birth under the conditions of myometrial scar. In the course of pregnancy and labor activity, the damage of the tissues was observed not in the uterine scar proper, but at its borders with the myometrium. This is supported by the old hemorrhages and lymphostasis phenomena, greater number of lymphocytes, neutrophils, monocytes, macrophages and erythrocytes. In determining the indications and contraindications to vaginal childbirth in women with scarred uterus it is necessary to examine not only the scar proper, but also its border with the myometrium. The myometrial scar by itself, is not an absolute contraindication to vaginal delivery, the natural delivery is feasible in the absence of cavities with liquid and hemorrhages in the tissues of the uterine scar and at its border with myometrium.

Pathomorphological analysis of internal endometriosis.

We performed clinical and morphological examination of 59 women with internal endometriosis (adenomyosis). Women were found to develop adenomyosis more frequently in the perimenopausal period (in their 40s) after repeated abortions and diagnostic surgical procedures. In 90% patients, adenomyosis was associated with the formation of multiple leyomyomatous nodules; glandular hyperplasia of the endometrium and fibrocystic transformation or fibrous degeneration of the ovaries were found in 60 and 100% cases. Two morphological variants of adenomyosis were identified: invasion of cytogenic stroma into the underlying myometrium with the formation of endometrial glands and invasion of cytogenic stroma via connective tissue interlayers without formation of endometrial glands and with pronounced neoangiogenesis. Foci of active adenomyosis in the uterus with predominance of cytogenic stroma were most prevalent in the late reproductive period. Endometrioid heterotopias were accompanied by considerable structural and functional reorganization of the myometrium with the formation of multiple leyomyomatous nodules. The presence of active and inactive adenomyosis foci and leyomyomatous nodules in uterus specimens reflects their metachronous development.

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.

[Absorbable suture material in the body].

Light microscopy was used to study postcesarean section uterine scars removed at resurgery and rat urine tissues after myometrial scar simulation. The myometrial scar tissue of 1 of 30 patients and 4 of 42 experimental animals exhibited vicryl suture material remains surrounded by a connective tissue capsule and, frequently, infiltrated leukocytes and giant cells of foreign bodies. It is not inconceivable that the presence of these foreign bodies in the tissues of the uterus and its scar may lower the strength of the wall of this organ during pregnancy and labor.

[A morphological analysis of the results of using the capron drainage-tampon with a sorbent for the treatment of acute nonspecific metroendometritis]. / Morfologicheskii analiz rezul'tatov primeneniia kapronovogo drenazh-tampona s sorbentom dlia lecheniia ostrogo nespetsificheskogo metroéndometrita.

The surface of carbon-mineral sorbent (CMS-1) granules and that of the capron cartridge were investigated using scanning electron microscopy in the course of acute nonspecific metroendometritis treatment after late abortion. The use of this sorbent for drainage of the uterine cavity decreases a toxic and antigenic effect on the organism. The use of the capron cartridge excludes the loose of the sorbent granules and their contact with the tissues, does not hinder the drainage and, at the same time, capron serves as a filter preserving active granule surface from a rapid disactivation by large fragments of tissue detritus.

[The artificial lymph node]. / K probleme iskusstvennogo limfaticheskogo uzla.

Adsorption of lymphocytes on the sorbents in correction of inflammatory lesions has significant clinical perspectives as the cells and active biological substances they secrete function actively in inflamed tissues acting in the site of its application: every cell adsorbs and inactivates foreign substances, every cytokin affects certain target cells. The products of these cells functioning and dissociation as well as the products of immune system reaction to them remain on the sorbent and are eliminated together with granules during bandaging or by the end of the treatment thus do not entering the organism. Lymphocytic monolayer on the sorbent does not prevent its specific action in pathologic nidus. In this case sorbent does not only drain the tissue duplicating certain primitive non specific functions of regional lymph node (barrier, filtrating, transport, draining and protective functions) but also performs certain highly specialized functions of immunocompetent organs--selective adsorption and inactivation of antigenic substances. It is reasonable to use sorbents for adsorbing lymphocytes in kapron containers which exclude the preparation leak into wounds and cavities and act as a filter preventing fast inactivation of the preparation by large fragments of tissue detritus.