The Experience of Using Multipotent Mesenchymal Stromal Cells in the Treatment of Severe Recurrent Cholangitis in Children with Biliary Atresia after Kasai Surgery.

This article describes the experience of application of multipotent mesenchymal stromal cells in the complex therapy of severe recurrent cholangitis in 2 children with biliary atresia after Kasai surgery. In both children, hepatic cellular insufficiency and portal hypertension developed against the background of long-term inflammatory process poorly controlled by standard therapy, which was the indication for liver transplantation. During the course of mesenchymal stromal cells therapy, the relief of the inflammatory process and functional recovery of the liver were achieved. At the time of preparing the article, the follow-up of two children since the start of multipotent mesenchymal stromal cell therapy was 3 years 9 months and 2 years 6 months. No recurrence of cholangitis was observed in the patients during the follow-up period, the liver function was preserved. There are no indications for liver transplantation at this moment. Thus, despite the fact that the mechanisms of therapeutic action of multipotent mesenchymal stromal cells in biliary atresia require further investigation, we obtained promising results suggesting the possibility of using mesenchymal stromal cells in the treatment of postoperative complications in children with biliary atresia.

[Significance of evaluation of CD69 expression by peripheral blood lymphocytes for predicting pregnancy outcome in women with recurrent pregnancy loss]. / Znachimost' otsenki ékspressii CD69 limfotsitami perifericheskoi krovi dlia prognoza iskhodov beremennosti u zhenshchin s privychnym vykidyshem.

The aim of this work was to characterize phenotypically peripheral blood T- and NK lymphocytes expressing an early marker of activation, CD69, and assess the significance of CD69 expression for predicting pregnancy outcome in women with idiopathic reccurent pregnancy loss (IRP) before and after immunocytotherapy (ICT). The study group consisted of 36 patients with IRP who became pregnant after pre-gestational allimmunization, in 30 patients the pregnancy was prolonged to the full term and ended with the birth of a viable baby, in 6 - it was terminated before 12 weeks of gestation. In the control group, 15 fertile women outside pregnancy and 11 women at 12 weeks of physiological pregnancy were examined. Assessment of the CD69 expression in women with prolonged pregnancy revealed the absence of significant differences with the control group in the content and proportion of activated lymphocytes (CD69+). In women with aborted pregnancy after pre-gestational ICT, an increase in the number of almost all analyzed lymphocyte subpopulations responding to the activation stimulus, with a clear tendency to increase the proportion of activated T- but not NK-lymphocytes was found. At 5-6 weeks, the proportion of activated lymphocytes among a subpopulation of cytotoxic T-lymphocytes (CD3+CD8+/CD3+CD8+CD69+) in these women was significantly higher than in women with prolonged pregnancy, which confirms the leading role of effector cytotoxic T-lymphocytes in rejection reactions. Thus, the studies showed the promise of evaluating the expression of the early activation marker CD69 as an additional laboratory criterion for the personable appointment of immunocytotherapy to women with a common reccurent pregnancy loss.

Lymphocyte Activation in the Development of Immune Tolerance in Women with Recurrent Pregnancy Loss.

Association between lymphocyte activation and formation of immune tolerance, as well as pregnancy outcome, in the case of immunocytotherapy (ICT) was studied in women with idiopathic recurrent pregnancy loss (IRPL). The content and phenotypic characteristics of activated T lymphocytes and NK cells were investigated in the peripheral blood of IRPL patients with different pregnancy outcomes (pregnancy prolongation to the full term and habitual miscarriage). The fraction of activated cells in the subpopulation of cytotoxic T lymphocytes (CD3+CD8+/CD3+CD8+CD69+) before ICT was significantly lower in women who lost the pregnancy. After ICT, the fraction of these cells during weeks 5-6 of pregnancy in woman with miscarriage was higher than in women with pregnancy prolonged to the full-term. Excessive content of activated cytotoxic lymphocytes can be a mechanism underlying impaired maternal immunotolerance to fetal alloantigens, which is a leading factor of early pregnancy loss. The obtained data confirm the involvement of activated Th17 cells and FOXP3+ Treg cells in the formation of tolerance to paternal antigens of the fetus. Comparison of the decrease in the fraction of CD4+CD25highRORγt+ lymphocytes at the early gestation period (5-6 weeks) and significant upregulation of the IL-17 production by in vitro stimulated whole blood cells in women with miscarriage with the same parameters in women with prolonged pregnancy suggested an imbalance between pro-inflammatory Th17 cells and Treg cells. No such imbalance in the content effector T lymphocytes was observed in women with the full-term pregnancy. Taken together, our data indicate an important role of gestational activation of lymphocytes in the formation of maternal immune response to fetal alloantigens necessary for the prolongation of pregnancy.