Stem cells as a model for studying the pathogenesis of the cardiovascular system diseases

 

Stem cells represent a valuable resource for the cell therapy in cardiovascular diseases. As for adults, most of stem cells are in the reside bone marrow and adipose tissue. Being a part of these tissues, mesenchymal stem cells (MSCs) fulfill a wide range of functions: provide trophism and support the other cells, synthesize and secrete growth factors and components of signaling cascades, moreover, mesenchymal stem cells (MSCs) show a high level of plasticity.

However, under some conditions, particularly due to the progression of cardiovascular diseases, heart failures and diabetes stem cells can behave differently, their proliferative and differential potential declines that complicate their application for cell therapy. As stem and progenitor cells fulfill essential biological functions in vivo, defining the course of growth, development, adaptation and regeneration and any problems occurring as the result of genetic, metabolic and other violations can lead to the delay in growth and development as well as reduce the adaptive and regenerative capacity of the body.

In 2009—2013 our institution participated together with 11 partners across Europe and Russia in a Collaborative Project “Study of molecular and cellular mechanisms of heart disease associated with diabetes and obesity” (SICA-HF) that was funded by the European Commission under the 7th Framework Program.

In this collaborative research project our main goal was to investigate how the functional properties of resident stem cells were affected in heart failure patients and heart failure comorbid with diabetes and/or obesity. Detailed clinical characteristics of participating patients, including cardiovascular and endocrine status, the body composition analysis, somnological disorders and psychological status were obtained in collaboration Institution of cardiovascular diseases. Therefore, in course of this project the collection of well characterized bone marrow- and subcutaneous adipose tissue-derived Mesenchymal Stem Cells (MSC) that includes samples from healthy donors and heart failure patients with and without comorbidities was accumulated. All cells were characterized for proliferative activity, plasticity, imunophenotype, replicative senescence, key cytokines expression and secretion and we have find out that these properties differ significantly between bone marrow- and adipose- derived MSC. We have also demonstrated that many functional properties are altered in MSC from heart failure patients and comorbidities enhanced these alterations even further. Now, using our MSC collection we have been working on development and evaluation of reliable cell culture models to study mechanisms of cardiovascular disorders in vitro, and to test in vitro how tissues respond at molecular levels to different physiological and pharmacological interventions.