AIMS. To investigate the efficacy of combination therapy using bone marrow-derived mesenchymal stromal cells (MSC) and Infliximab (IFX) to achieve «deep remission» in patients with luminal Crohn disease (CD). METHODS. Our study included 72 patients (19-62 y old) (Ме=29) with luminal CD. Patients ini group (n=21) received standard 5-aminosalicylic acid (5-ASA) and glucocorticosteroids (GCS) therapy in combination with MSC. Patients in 2 group (n=32) were prescribed anti-cytokine therapy IFX. Patients in 3 group (n=19) received MSC and IFX. RESULTS. Clinical, immunobiological and hystological results (C-reactive protein-CRP, fecal calprotectin-FCP, Gebs scale) showed more significant decrease of local and systemic inflammation activity in 3 group of patients. During 3-year follow-up we observed the longer duration of remission in patients, received MSC and IFX compared to 1 group of patients (р=0,04) and 2 group of patients (р=0,038). CONCLUSIONS. Combination therapy of bone marrow-derived MSC and IFL provides «deep remission» in patients with luminal CD and has higher prognostic value in duration of CD remission period.
Using stem cells as an example the review considers a new history and methodology of search for stem cells (SC), found in tissues of adult Homo sapiens and Drosophila melanogaster organisms. These studies of SC resulted in several original hypotheses explaining their unusual features. Impressive progress recently achieved in this direction (2008-2010) is associated with employment of new methods of somatic recombination for long-term registration of various strains of differentiated cells, early and distant SC progeny. 1) Although anatomic localization of intestinal epithelium cells lacking marked morphological and biochemical differentiation markers (the lower third of intestinal and colon crypts) is known for about 40 years results of their experimental identification, isolation and detection of their functional characteristics still represent the subject for discussions. Particularly, it remains unclear, which SC are involved in crypt regeneration: the same as those involved into homeostatic renewal or their various subpopulations or early SC progenies acquired stem features by reprogramming? 2) In addition, most detected biochemical markers of potential SC are common for SC from other tissues of embryonic and mature organisms so it is possible to apply method developed for intestinal epithelium for their isolation. 3) Data on induction of intestinal epithelium polyps and neoplasias by mutations in genes encoding SC markers and identification of biochemical characteristics of potential SC in these tumors support the hypothesis of stem tumor cell origination from normal SC or their earliest progeny. In general, facts considered in this review may be useful for both development of optimal methods for the use of SC in cell therapy (as the source of humoral factors), regenerative medicine (as the source of differentiated cells for restoration of injured tissue), and also for targeted search of antitumor drugs (SC as the target) and preparations modifying genetic and epigenetic reactions of SC to genotoxic and stress treatments.
Цель работы: сравнить результаты лечения двух групп больных с острой атакой язвенного колита, получающих стандартную терапию и терапию с применением культуры аллогенных мезенхимальных стволовых клеток. По результатам проведенной работы установлено, что введение культуры МСК повышает эффективность противовоспалительной терапии у больных с острой атакой ЯК Ключевые слова: биологическая терапия, воспалительные заболевания кишечника, мезенхимальные стволовые клетки, язвенный колит Aim: to compare the mid-term results of treatment of patients with acute attack of moderate and severe ulcerative colitis receiving standard anti-inflammatory therapy and integrated anti-inflammatory therapy using allogeneic culture of mesenchymal stem cells of bone marrow. Materials and methods. Patients with acute attack of ulcerative colitis were divided into two groups. The first group of patients with UC (n=12) in addition to standard anti-inflammatory therapy, received the culture of mesenchymal stem cells (MSC). The second group of patients (n=10) received standard anti-inflammatory therapy with 5-aminosalicylic acid (5-ASA) and glucocorticosteroids (GCS). The clinical activity of UC was assessed on a scale D. Rachmilewitz endoscopic picture was assessed on a scale of Mayo. The duration of remission in groups of patients was estimated by the method of Kaplan-Meier. Results. The original index of Rachmilevitz and the index of Mayo in both groups were comparable. In a year from the start of the study, the risk of recurrence of ulcerative colitis, duration of remission, indices of clinical and endoscopic activity in both groups of patients were comparable. After two years, the effectiveness of anti-inflammatory therapy on major indicators was higher in the group of patients treated with MSC. However, after 3 years of follow-up in both groups clinical and endoscopic indices showed no significant differences. Conclusion. The introduction of a culture of MSC increases the effectiveness of anti-inflammatory therapy in patients with acute attack of ulcerative colitis, increases the duration of disease remission, reduces to 3 times the risk of attack within 2 years of observation
Cell therapy is one of the most promising directions in the treatment of critical limb ischemia (CLI). In spite of certain advances achieved in this field in the last decades, which are related to application of bone marrow stem cells (BMSC), a large number of problems still remain unsolved. In this review, we discuss the BMSC biology, mechanisms of their therapeutic effect in the CLI treatment and results of the most notable BMSC-based clinical studies in detail.
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