Controlled immunocorrection and subsequent activation of bone marrow mononuclear cells improve myocardial function in chronic ischemic cardiac failure

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Abstract

Chronic cardiac failure is accompanied with immune dysregulation which severity predetermines the absence of clinic efficiency of autologous bone marrow stem cells (BMSCs). The effect of two-staged activation of bone marrow stem cells (at first, in vivo, then ex vivo) on left ventricle function promotion in patients with chronic cardiac failure has been studied. Two groups of patients with chronic cardiac failure took part in the investigation. The 1st group patients (control, n=50) underwent cardiopulmonary bypass. To the patients of the 2nd group (n=57) 200 mln autologous mononuclear marrow stem cells were introduced intramyocardially during the cardiopulmonary bypass. In the 2nd group patients the original immune dysregulation severity was assessed by assaying the index of white blood cells stimulation (SI) with a chemoluminescent test. In 16 patients with SI>1 and a moderate alteration of immunoassay favorable effect of BMSCs was predicted; bone marrow stem cells were predicted to produce unfavorable clinic effect in 41 patients with SI <1 and profound alterations of immunoassay. 22 patients with SI <1 had undergone immunocorrecting therapy (stem cells in vivo activation). Mononuclear stem cells of patients (n=38 with SI>1 and n=19 with SI<1) were cultured for 5-7 days (stem cells ex vivo activation). The research demostrated that BMSCs culturing in patients with favorable prognosis led to the changes of immunophenotype of bone marrow such as CD3, CD4, CD8, CD 25 increase. The control examination of the patients 6 months after autologous bone marrow cells introduction revealed that positive dynamics of the left ventricle function and the physical activity index (DASI) occurred in patients with SI>1. Controlled immunocorrection performed before derivation of BMSCs, in combination with their subsequent ex vivo activation promoted reliable improvement of functional characteristics of the left ventricle 6 months after cardiopulmonary bypass in comparison with the controls. For autologous bone marrow stem cells to be effective in patients with chronic cardiac failure two-staged activation of BMSCs should be performed: at first, in vivo with immunocorrectors, then ex vivo while culturing.

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About the authors

A. A. Temnov

State Scientific Research Institute of Transplantology and Artificial Organs, Russian Ministry of Рublic Health

Author for correspondence.
Email: redaktor@celltranspl.ru

Laboratory of stem cells biotechnology

Russian Federation, Moscow

S. V. Gureev

State Scientific Research Institute of Transplantology and Artificial Organs, Russian Ministry of Рublic Health

Email: redaktor@celltranspl.ru

Laboratory of stem cells biotechnology

Russian Federation, Moscow

N. A. Onishchenko

State Scientific Research Institute of Transplantology and Artificial Organs, Russian Ministry of Рublic Health

Email: redaktor@celltranspl.ru

Laboratory of stem cells biotechnology

Russian Federation, Moscow

V. I. Shumakov

State Scientific Research Institute of Transplantology and Artificial Organs, Russian Ministry of Рublic Health

Email: redaktor@celltranspl.ru

Laboratory of stem cells biotechnology

Russian Federation, Moscow

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