Adenomyosis, previously termed “endometriosis interna,” is a widespread disease affecting the female reproductive system and frequently resulting in infertility in women. The aim of this work was to examine the properties of endometrial mesenchymal stem cells (eMSCs) from a patient with adenomyosis. We established the cell line from a patient with adenomyosis and compared the properties of these cells with cells derived from a healthy donor. It was found that patient-derived eMSCs and eMSCs from healthy donors had a fibroblast-like morphology and did not differ in expression of surface markers and adipogenic potential. Karyotype analysis of G-banded metaphase chromosomes was performed in cells of both lines at the six or seventh passages. Cells from the healthy donor mostly had normal karyotype. Karyotype of eMSCs from the patient with adenomyosis usually had chromosomal abnormalities. The abnormalities concerned aneuploidy and nonrandom chromosomes breaks more often involving chromosomes 7 and 11. Although karyotype instability may be a sign of cell transformation, the patient-derived eMSCs stopped cycling after about 26 passages and entered into replicative senescence. This shows that the karyotypic abnormalities that we observed in adenomyosis-derived eMSCs are not relevant to the cell transformation and immortalization in vitro.

Adenomyosis is form of endometriosis, common diseases of female reproductive system, which can lead to infertility in women. in this study we are obtained and characterized cell line endometrial mesenchymal stem cells from a patient with adenomyosis, and compare obtained cells with the cell line of healthy donor. Aim of this study was to assesses the extent of differences between cells from donor with adenomyosis and cells from healthy donor. Was established that compared lines had morphology like fibroblasts, were differentiated in adipocytes, were expressed mesenchymal markers and didn't expressed haematopoietic markers. Cytogenetic analysis of differentially stained metaphase chromosomes on G-banding (passage 6-7) showed that healthy donor's cells had predominantly normal karyotype. The cellular line from a patient with diagnosis of "adenomyosis" had a lot of cells with changes in karyotype's structure. These changes were related with aneuploidy of cellular population and the presence non-random chromosomal breaks, often in chromosomes 7 and 11. Analysis of this data allows the cells from adenomyosis characterized physiological stability in culture and karyotypic instability with non-random involvement certain chromosomal set. The cellular line obtained from donor with adenomyosis showed signs destabilization of he genome, typical for cell transformation. Division of adenomyosis cells to the 26th passage is stopped and these cells entered into a phase of replicative aging. Based on this, we can conclude that founded karyotype's hanges do not lead to transformation and immortalization of cells in vitro.

We transplanted syngenetic bone marrow mesenchymal stem cells (BM MSCs) obtained from 3- to 4-month-old or 20- to 22-month-old donors into the brain of 22- to 24-month-old male Wistar–Kyoto rats. Using a TV device to study microcirculation in vivo, we found that transplantation of BM MSCs from young donors increased the densities of the microvascular network in the pia mater of the sensorimotor cortex and of the arteriolar compartment in old rats approximately by values of 1.9 and 2.1 as compared to agematched controls. Transplantation of BM MSCs from old donors did not significantly influence the density of the microvascular network in the pia mater, while the density of the arteriolar compartment increased by approximately 1.5 times.

Using a TV device to study microcirculation in brain we found that intracerebral transplantation of mesenchymal stem cells to 12-months old rats led to a significant increase (circa 1,5-fold times) of microvascular density in pia tissue and to increased constriction reactions of pia arterioles in response to noradrenalin application on a brain surface. Both microvascular density and pia arterioles reactivity was completely preserved in aging until 22-24 months.

Parkinson's disease (PD) is a common, progressive neurodegenerative disorder associated with a loss of dopaminergic cells in the substantia nigra pars compacta and a lack of dopamine in the striatum. To halt or reverse this disease, neurorestorative approaches or neuroprotective treatments are urgently needed. Recently, the first clinical trials transplanting mesenchymal stem cells (MSCs) have been performed in PD. MSCs are adult stem cells abundant in several tissues, such as the umbilical cord, the bone marrow, the adipose tissue and other tissues. These cells are multipotent, and able to synthesize and secrete a wide spectrum of biologically active factors. MSCs of various origins have been explored as possible substrates for cell therapy in PD animal models. In this review, we summarize MSC-based experimental transplantation studies in PD, and discuss biological mechanisms that may explain the effects of MSC seen in PD models. Furthermore, we critically evaluate the recent clinical transplantation trials using MSCs in patients with PD.

The ability of mesenchymal stem cells (MSCs) to differentiate into neuronal lineage determines the potential of these cells as a substrate for a cell replacement therapy. In this paper we compare the neurogenic potential of the MSCs from different donors, isolated from the bone marrow (BMSC), subcutaneous adipose tissue (AD MSC) and menstrual blood (eMSC). It was established that the native eMCSs, BMSCs and AD MSCs express neuronal marker β-III-tubulin with a frequency of 90, 50 and 14%, respectively. Also we showed that the eMSCs have a high endogenous level of brain-derived neurotrophic factor (BDNF), whereas the BMSCs and the AD MSCs are characterized by low basal BDNF levels. An induction of neuronal differentiation in the studied MSCs using differentiation medium containing B27 and N2 supplements, 5-azacytidine, retinoic acid, IBMX and dbcAMP induced changes in the cells morphology, the increase of β-III-tubulin expression, and the appearance of neuronal markers GFAP, NF-H, NeuN and MAP2. During the differentiation the BDNF secretion was significantly enhanced in the BMSCs and decreased in the eMSCs cultures. However, no correlation between the basal and induced levels of the neuronal markers expression in the studied MSCs has been established.

Tissue engineered vascular grafts can fulfill a clinical need in biological prostheses in reconstructive cardiovascular surgery. Decellularized arteries do not cause immune response, are biocompatible, could be reseeded with recipient cells und thus are attractive scaffolds for vascular tissue engineering. Earlier we developed a decullarization method for human umbilical arteries and proved its effectiveness morphologically. The purpose of this study was to evaluate mechanical properties of the decellurized human umbilical arteries, also after long-term storage. 3 groups of vessels were investigated: I group - native arteries, II group - decellularized arteries, III group - decellularized arteries, stored in phosphate buffered saline for 10 months. Samples were stretched until rupture on the Instron universal testing machine; herewith strain and stress were recorded. The same way the suture retention strength was estimated. Also burst-pressure, that characterized the total strength of the samples, was investigated. Intergroup differences in maximum strain both longitudinal and transverse directions, suture retention strength and burst pressure were not significant. Decellularized human umbilical arteries retain their mechanical properties, and that indirectly confirms extracellular matrix preservation. Thus they are attractive source for small diameter tissue engineered vascular grafts.

Using a television-based vital microscopy method and immunohystochemical analysis, we have assessed the effect of intracerebral transplantation of syngeneic mesenchymal stem cells (MSC) on the brain cortex structure and the microcirculation in the pia mater of old rats. Using "open field" system, we have studied the effect of MSC transplantation on position-finding and discovery behavior of older animals. We have found that density of microvascular network of the pia mater increased ca. 1.9-fold in MSC recipients, compared to age-matched intact animals. Density of the arteriolar area of microvascular network of the pia mater increased ca. 2-fold. Reactivity of the newly formed arterioles was nearly equal to that of native microvessels. Intracerebral transplantation procedure itself was traumatic for brain cortex of rats, but it had no effect on the microcirculation in the contralateral hemisphere. Intracerebral transplantation of MSC did not improve locomotor behavi- or and emotional stage of old rats, did not increase their position-finding and discovery activity.

Male Wistar-Kyoto rats (12 and 22–24 months old) were intracerebrally transplanted with syngeneic mesenchymal stem cells (MSCs). Then, the orientation and exploratory behavior of these animals at the age of 2 years (i.e., 1 year or 3 weeks after MSC transplantation) was assessed in an “open field” test. The basic behavioral acts of the older rats (22–24 months old) were inhibited compared to the younger animals (2–3 months old). The transplantation of MSCs did not improve the orientation and exploratory behavior of old rats. The results of morphological and immunohistochemical analysis suggest that the intracerebral MSC transplantation led to partial injury of the ipsilateral hemisphere cortex.

Male Wistar-Kyoto rats aged 22-24 months were intracerebrally transplanted with syngenic bone marrow mesenchymal stem cells (BM MSC) established from the donor aged 3-4 months and 20-22 months, respectively. Using a TV device to study microcirculation in vivo, we have established that transplantation of BM MSC from young donors increased a density of the microvascular network in the pia mater of the sensorimotor cortex in old rats approximately 1.9-fold, comparing to age-matched controls, while a density of the arteriolar compartment increased approximately 2.1-fold. Transplantation of BM MSC from old donors did not lead to the significant increase in the density of the microvascular network in the pia mater, while a density of the arteriolar compartment increased approximately 1.5-fold.

Future NeurologyVol. 9, No. 1 EditorialStem cell therapy for neurodegenerative diseases: mind the gapSergey V AnisimovSergey V AnisimovResearch Unit of Cellular & Genetic Engineering, VA Almazov Federal Center for Heart, Blood & Endocrinology, Akkuratova Street 2, Saint Petersburg, 197341, Russiaand Department of Intracellular Signaling & Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg, Russia. Published Online:16 Dec 2013https://doi.org/10.2217/fnl.13.64AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: adult stem cellscell therapyclinical trialsembryonic stem cellsfundamental researchinduced pluripotent stem cellsrisksstem cellstransplantationReferences1 Drummond-Barbosa D. Stem cells, their niches and the systemic environment: an aging network. 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The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download

Small diameter tissue engineered vascular grafts could be a potential solution to the shortage of vascular substitutes in reconstructive cardiovascular surgery. Previously, we have developed a decellularization method for human umbilical arteries, which could be used as a scaffold in vascular tissue engineering. Objective of the study was to optimize the recellelularization of decellularized scaffolds with mesenchymal stem cells. In the study, the possibility of cell growth on decellularized vessel has been shown. We also has proved that the use of perfusion-bioreactor improves the results of recellularization.

It is proposed that patients with heart failure may have not only myocardial dysfunction, but also a reduced regenerative capacity of stem cells. However, very little is known about bone marrow stromal cell (BMSC) characteristics in heart failure and its comorbidities (obesity and/or diabetes). We hypothesized that metabolic alterations associated with the latter will be reflected in altered expression of key genes related to angiogenesis, inflammation, and tissue remodeling in patient-derived BMSCs. We found that BMSCs of heart failure patients with lower body mass index have enhanced expression of genes involved in extracellular matrix remodeling. In particular, body mass index <30 was associated with upregulated expression of genes encoding collagen type I, proteases and protease activators (MMP2, MMP14, uPA), and regulatory molecules (CTGF, ITGβ5, SMAD7, SNAIL1). In contrast, these transcript levels did not differ significantly between BMSCs from obese heart failure patients and healthy subjects. Comorbidities (including obesity and diabetes) are known to play role in heart failure progression rate and outcome of the disease. We thus suggest that key molecular targets identified in this study should become the target of the subsequent focused studies. In the future, these targets may find some use in the clinical setting.

Using a TV device for studying microcirculation (×160), we analyzed the responses of arterioles in the pia mater of the sensorimotor cortex in young (2-3 months) and old (22-24 months) rats after local application of a vasoconstrictor (norepinephrine, 10–6 M) or vasodilator (acetylcholine, 10–6 M). The responses of the arterioles were evaluated by changes in their diameter and by the number of responding vessels in the field of view. The constrictor responses of the pial arteries to norepinephrine did not significantly differ in intact young and old rats. The number and degree of dilatory responses to acetylcholine in old rats were lower than in young animals by 14 and 30%, respectively. Intracerebral transplantation of mesenchymal stem cells to old rats had practically no effect on reactivity of pial arterioles to acetylcholine, while the number of constricted vessels in response to norepinephrine increased by ~20%.

We studied the effect of intracerebral transplantation of bone marrow mesenchymal stem cells on microcirculation (density of microvascular network and reactivity of arterioles) in the pia mater of 2-3-month-old rats. It was found that after transplantation of mesenchymal stem cells, the density of pial microcirculatory network in the contralateral hemisphere significantly increased (by 1.7 times; p <0.05) in comparison with both intact animals and controls. The number of arterioles in the studied area increased most markedly (by ~2.5 times; p <0.05) in comparison with other groups. Intracerebral transplantation of mesenchymal stem cells or conditioned culture medium (α-MEM) had no effect on reactivity of pial arterioles.

Study aim - to elucidate possibilities of the use of precision administration of mononuclear bone marrow cells (MBMC) for the treatment of myocardial ischemia and heart failure. "Intramyocardial Multiple Precision Administration of Mononuclear Bone Marrow Cells in the Treatment of Myocardial Ischemia" was a double blind randomized placebo controlled study in which we included patients more or equal 6 months after Q-wave myocardial infarction with systolic myocardial dysfunction (ejection fraction <35%), not requiring myocardial revascularization, receiving stable optimal medical therapy for more or equal 8 weeks, and with implanted cardioverter-defibrillator. Transplantation of MBMC was guided by fluoroscopy and tridimensional NOGA XP Cardiac Navigation System. For assessment of efficacy of the method we used surrogate end points: decrease of number of fixed perfusion defects according to SPECT data and improvement of regional myocardial contractility according to data of echocardiography. Results of dynamic observation of the first experience of MBMC administration are presented in this paper.