PubMed | Research Center for Obstetrics
Type: | Journal: Stem cell research & therapy | Year: 2016
Mesenchymal stromal/stem cells derived from human umbilical cord (UC-MSCs) uniquely combine properties of embryonic and postnatal MSCs and may be the most acceptable, safe, and effective source for allogeneic cell therapy e.g. for therapeutic angiogenesis. In this report we describe pro-angiogenic properties of UC-MSCs as manifested in vitro.UC-MSCs were isolated from human Whartons jelly by enzymatic digestion. Presence of soluble forms of VEGF-A in UC-MSC-conditioned media was measured by ELISA. Effects of the conditioned media on human umbilical vein-derived endothelial EA.hy926 cells proliferation were measured by MTT-assay; changes in cell motility and directed migration were assessed by scratch wound healing and transwell chamber migration assays. Angiogenesis was modeled in vitro as tube formation on basement membrane matrix. Progressive differentiation of MSCs to endothelioid progeny was assessed by CD31 immunostaining.Although no detectable quantities of soluble VEGF-A were produced by UC-MSCs, the culture medium, conditioned by the UC-MSCs, effectively stimulated proliferation, motility, and directed migration of EA.hy926 cells. In 2D culture, UC-MSCs were able to acquire CD31(+) endothelial cell-like phenotype when stimulated by EA.hy926-conditioned media supplemented with VEGF-A165. UC-MSCs were capable of forming unstable 2D tubular networks either by themselves or in combinations with EA.hy926 cells. Active spontaneous sprouting from cell clusters, resulting from disassembling of such networks, was observed only in the mixed cultures, not in pure UC-MSC cultures. In 3D mode of sprouting experimentation, structural support of newly formed capillary-like structures was provided by UC-MSCs that acquired the CD31(+) phenotype in the absence of exogenous VEGF-A.These data suggest that a VEGF-A-independent paracrine mechanism and at least partially VEGF-A-independent differentiation mechanism are involved in the pro-angiogenic activity of UC-MSCs.
PubMed | Scientific Research Institute of Human Morphology and Research Center for Obstetrics
Type: Journal Article | Journal: PloS one | Year: 2016
Proliferation of hepatocytes is known to be the main process in the hepatectomy-induced liver regrowth; however, in cases of extensive loss it may be insufficient for complete recovery unless supported by some additional sources e.g. mobilization of undifferentiated progenitors. The study was conducted on rat model of 80% subtotal hepatectomy; the objective was to evaluate contributions of hepatocytes and resident progenitor cells to the hepatic tissue recovery via monitoring specific mRNA and/or protein expression levels for a panel of genes implicated in growth, cell differentiation, angiogenesis, and inflammation. Some of the genes showed distinctive temporal expression patterns, which were loosely associated with two waves of hepatocyte proliferation observed at 2 and 7 days after the surgery. Focusing on genes implicated in regulation of the progenitor cell activity, we came across slight increases in expression levels for Sox9 and two genes encoding tumor necrosis factor-like cytokine TWEAK (Tnfsf12) and its receptor Fn14 (Tnfrsf12a). At the same time, no increase in numbers of cytokeratin 19-positive (CK19+) cells was observed in periportal areas, and no CK19+ cells were found in hepatic plates. Since CK19 is thought to be a specific marker of both cholangiocytes and the hepatic progenitor cells, the data indicate a lack of activation of the resident progenitor cells during recovery of hepatic tissue after 80% subtotal hepatectomy. Thus, proliferation of hepatocytes invariably makes the major contribution to the hepatic tissue recovery, although in the cases of subtotal loss this contribution is distinctively modulated. In particular, induction of Sox9 and TWEAK/Fn14 regulatory pathways, conventionally attributed to progenitor cell activation, may incidentally stimulate mitotic activity of hepatocytes.
PubMed | Russian National Research Medical University, RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Medical Sciences and Research Center for Obstetrics
Type: | Journal: Stem cells international | Year: 2015
Cell therapy is increasingly recognized as a beneficial practice in various cardiac conditions, but its fundamentals remain largely unclear. The fates of transplanted multipotent stromal cells in postinfarction cardiac microenvironments are particularly understudied. To address this issue, labeled multipotent stromal cells were infused into rat myocardium at day 30 after myocardial infarction, against the background of postinfarction cardiosclerosis. Therapeutic effects of the transplantation were assessed by an exercise tolerance test. Histological examination at 14 or 30 days after the transplantation was conducted by means of immunostaining and quantitative image analysis. An improvement in the functional status of the cardiovascular system was observed after both the autologous and the allogeneic transplantations. Location of the label-positive cells within the heart was restricted to the affected part of myocardium. The transplanted cells could give rise to fibroblasts or myofibroblasts but not to cardiac myocytes or blood vessel cells. Both types of transplantation positively influenced scarring processes, and no expansion of fibrosis to border myocardium was observed. Left ventricular wall thickening associated with reduced dilatation index was promoted by transplantation of the autologous cells. According to the results, multipotent stromal cell transplantation prevents adverse remodeling and stimulates left ventricular reverse remodeling.
News Article | November 18, 2016
Laureates to be recognized by Research and Academic Leaders at Awards Ceremony on December 1st in Moscow The organizers of Prix Galien Russia have today released the nominees for the third edition of the Awards. The Prix Galien Russia Committee (or Jury) comprises 15 renowned leaders in biomedical research and academia and is responsible for evaluating nominees based on scientific files. Laureates will be honored at the Prix Galien Russia Awards Ceremony at Volkhonka Mansion, on the 1st of December 2016 The Prix Galien Russia Committee designates a laureate in 6 different categories by evaluating scientific applications files submitted by the candidates based solely on two questions: Frederic Boucheseiche, General Secretary of Prix Galien Russia, reiterated the uniqueness and importance of Prix Galien by emphasizing the fact that the Jury's decision is based only on scientific and medical criteria, that marketing and commercial considerations never enter into the Jury's decision, and by restating that pharmaceutical companies cannot sponsor the event. "Organizing an awards ceremony under such strict principles is extremely challenging, but this is the condition that guarantees the impartiality of the jury's decision. Prix Galien Russia uses the same strict criteria as in all other countries where the award is held, making its legitimacy indisputable." Frederic Boucheseiche. Nominees for the Prix Galien Russia 2016 Awards are: Development of a new generation of Antivirals of the family of azoloazines - Institute of Organic Synthesis OncoFinder platform for personalized selection of drugs in oncology - First Oncology Research and Advisory Center ImmunoQuantex "Femoflor®"+ «ImmunoQuantex" - DNA-Technology LLC/ Federal State Budget Institution "Research Center for Obstetrics, Gynecology and Perinatology" Ministry of Healthcare of the RF Prix Galien Russia was inaugurated in Moscow in 2013 under the auspice of an exceptional awards committee composed of eminent specialists involved in the sphere of Russian and international pharmaceutical research. A Prix Galien Award is considered the biomedical industry's highest accolade and recognizes the technical, scientific and clinical research skills necessary to develop innovative medicines. Around the world, Prix Galien rewards outstanding achievements in improving the global human condition through the development of innovative therapies. Created in France 40 years ago, Prix Galien has selection committees in 16 countries around the world.
News Article | December 2, 2016
On Thursday, December 1st 2016, the Prix Galien Russia Awards Committee honored excellence in research, development and innovation in the biopharmaceutical industry at its third awards ceremony. The gala dinner was held in the presence of Sergey Tsyb, Vice Minister of Industry and Trade of the Russian Federation, Natalia Sanina, First Vice Chairman of the State Duma Healthcare Committee; Mikhail Murashko, Head of Roszdravnadzor, National Service of Control in Healthcare, Sergey Muravev, Director of the Department of International Cooperation and Public Relations, and Igor Lanskoy, Advisor to the Minister of Health of the Russian Federation among others. For the third time in history, the Prix Galien Russia Awards Committee, a Jury of 15 unrivalled Russian scientists and doctors, including academicians of the Russian Academy of Sciences, recognized leading efforts in advancing the human condition through biopharmaceutical innovation in six categories: Best Orphan Drug, Best Pharmaceutical Agent, Best Biotechnology Product, Best Medical Technology, Best Research in Russia and Best Russian Product. The Prix Galien Russia 2016 awards were presented to the following winners: In the category of Best Orphan Drug the award was presented to Amgen's Blinatomubab, for the treatment of Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL). Blinatumomab overcomes the effect of tumor escape from the immune system. Due to its unique mechanism of immune effect, blinatumomab does not inhibit hematopoiesis, this sets up blinatumomab from cytotoxic agents, exhibiting a myelosuppressive effect, which limits their therapeutic options. The Medal was presented to Oleg Paroshin, CEO of Amgen Russia by Ekaterina Zakharova, President of the Association of rare diseases. The 2016 Prix Galien Russia Award for Best Pharmaceutical Agent was presented to Janssen's (Pharmaceutical Companies of Johnson&Johnson) - Imbruvica® (Ibrutinib) for chronic lymphocytic leukaemia. Ibrutinib is the first BTK inhibitor to offer patients a novel, targeted treatment that combines unparalleled efficacy and good tolerability with the convenience of oral dosing. In the category of Best Biopharmaceutical Product, the 2016 Prix Galien Russia Award was presented to Bristol-Myers Squibb's Yervoy® (Ipilimumab) for treatment of previously treated unresectable or metastatic melanoma. The 2016 Prix Galien Russia Award for Best Medical Technology was presented to Abbott's Absorb Bioresorbable Vascular Scaffold. Absorb is the world's first drug eluting bioresorbable vascular scaffold (BVS) for the treatment of coronary artery disease. Absorb is designed to open a blocked heart vessel in the same way as a traditional metallic stent and then dissolve naturally. In the category of Best Research in Russia the award went to Valery Charushin, Oleg Chupakhin and Vladimir Rusinov for their work on the development of a new generation of antivirals of the family of azoloazines. The 2016 Prix Galien Russia Award for Best Russian Product was presented to the DNA-Technology and Federal State Budget Institution "Research Center for Obstetrics, Gynecology and Perinatology" Ministry of Healthcare of the Russian Federation "Femoflor®"+"ImmunoQuantex®" for differential and complex diagnosis of different clinical condition connected with dysbiotic disorders and inflammatory conditions of the lower reproductive tract of women. On the occasion of World HIV day, the Jury also honoured E. Zvartau, E. Krupitsky, D.Lioznov, G.Woody, J. Samet with a special distinction for their work on the prevalence of HIV in vulnerable and special populations of the Russian Federation. Reading a letter received by Veronika Skvortsova, Igor Lanskoi, adviser to the minister declared that "for many years, this has been one of the most coveted awards in the field of biopharmaceutical research, opening new perspectives for the improvement of medical science". Michael Murshko, presenting the medal for Best Research in Russia declared "healthcare cannot develop without innovations and the Prix Galien award is a successful example of support for new improvements in biomedical science, the main purpose of which is to provide patients with quality and effective medical products". Representing the State Duma for the first time at the event, Natalia Petrovna Sanina declared "Prix Galien is not just an award, it is a movement aimed at searching for and promoting scientific innovations that contribute to people's health".
Shamilova N.N.,Research Center for Obstetrics |
Marchenko L.A.,Research Center for Obstetrics |
Dolgushina N.V.,Research Center for Obstetrics |
Zaletaev D.V.,Moscow State University |
Sukhikh G.T.,Research Center for Obstetrics
Journal of Assisted Reproduction and Genetics | Year: 2013
Purpose: To identify the role of both genetic (number of CGG repeats in the FMR1 gene) and autoimmune factors (anti-ovarian antibodies) in premature ovarian failure (POF). Methods: In cross-sectional study, 78 women with POF were divided into 3 groups by the number of CGG repeats (less than 28, 28-36, more than 36) in any of the FMR1 gene alleles. We performed the detection of skewed X-chromosome inactivation, CGG repeats in the FMR1 gene, anti-ovarian antibodies (AOA) and sex hormones tests. Results: Compared to a higher or lower number of CGG repeats the 28-36 triple CGG counts are strongly associated with the AOA detection (RR = 19.23, 95 % CI = 2.63-100.0). The women with autoimmune-driven POF have significantly higher anti-Mullerian hormone levels in comparison to women with non-autoimmune-driven POF. Conclusion: The presence of AOA above 10 IU/mL is associated with the normal number of CGG repeats in regard to ovarian reserve and a better preservation of follicular primordial pool in the women with POF. © 2013 Springer Science+Business Media New York.
Yarygin K.N.,RAS V.N. Orekhovich Institute of Biomedical Chemistry |
Lupatov A.Y.,RAS V.N. Orekhovich Institute of Biomedical Chemistry |
Sukhikh G.T.,Research Center for Obstetrics
Bulletin of Experimental Biology and Medicine | Year: 2016
This concise review provides an assessment of one of the most conceptually and practically important properties of mesenchymal stromal cells, their ability to modulate immune responses, including underlying cellular and molecular mechanisms and prospects of clinical application in the treatment of autoimmune and other immunological disorders. © 2016 Springer Science+Business Media New York
PubMed | Russian National Research Medical University and Research Center for Obstetrics
Type: | Journal: Stem cells international | Year: 2016
The paper presents current evidence on the properties of human umbilical cord-derived mesenchymal stem cells, including origin, proliferative potential, plasticity, stability of karyotype and phenotype, transcriptome, secretome, and immunomodulatory activity. A review of preclinical studies and clinical trials using this cell type is performed. Prospects for the use of mesenchymal stem cells, derived from the umbilical cord, in cell transplantation are associated with the need for specialized biobanking and transplant standardization criteria.
PubMed | University of Texas Medical Branch and Research Center for Obstetrics
Type: | Journal: Scientific reports | Year: 2016
Preeclampsia (PE) is a pregnancy-specific syndrome, characterized in general by hypertension with proteinuria or other systemic disturbances. PE is the major cause of maternal and fetal morbidity and mortality worldwide. However, the etiology of PE still remains unclear. Our study involved 38 patients: 14 with uncomplicated pregnancy; 13 with early-onset PE (eoPE); and 11 with late-onset PE (loPE). We characterized the immunophenotype of cells isolated from the placenta and all biopsy samples were stained positive for Cytokeratin 7, SOX2, Nestin, Vimentin, and CD44. We obtained a significant increase in OPA1 mRNA and protein expression in the eoPE placentas. Moreover, TFAM expression was down-regulated in comparison to the control (p<0.01). Mitochondrial DNA copy number in eoPE placentas was significantly higher than in samples from normal pregnancies. We observed an increase of maximum coupled state 3 respiration rate in mitochondria isolated from the placenta in the presence of complex I substrates in the eoPE group and an increase of P/O ratio, citrate synthase activity and decrease of Ca(2+)-induced depolarization rate in both PE groups. Our results suggest an essential role of mitochondrial activity changes in an adaptive response to the development of PE.
PubMed | RAS V.N. Orekhovich Institute of Biomedical Chemistry and Research Center for Obstetrics
Type: Journal Article | Journal: Bulletin of experimental biology and medicine | Year: 2016
This concise review provides an assessment of one of the most conceptually and practically important properties of mesenchymal stromal cells, their ability to modulate immune responses, including underlying cellular and molecular mechanisms and prospects of clinical application in the treatment of autoimmune and other immunological disorders.