The adoption of expansion strategies of bone marrow derived mesenchymal stromal cells from patients with heart failure and co-morbidities

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Abstract

Autologous transplantation of bone marrow derived multipotent mesenchymal stromal cells is considered as a promising treatment for cardiovascular diseases including heart failure. The phenotype of patient with heart failure changed over the last two decades: the percentage of very old individuals, and number of comorbidities increased markedly. These factors could affect the functional properties of mesenchymal stromal cells intended for autologous transplantation. In this study for a first time the functional properties of cell samples from patients with heart failure and co-morbidities (obesity and diabetes mellitus) were investigated and the possibilities to compensate for the effects of patient factors on stromal cell properties by correcting ex vivo expansion strategies were studied. 10 healthy donors, 16 with isolated heart failure, 21 with comorbid obesity, 3 with diabetes and 9 with obesity and diabetes were enrolled. Cultures were evaluated in successive passages for immunophenotype, proliferative activity (population doubling time), frequency of colony-forming units, frequency of adipo- and osteo-progenitors at different seeding density under hypoxia/normoxia. The proliferation rate of mesenchymal stromal cells from patients with heart failure and co-morbidities decreased at early passages while seeded at 3000 cells/ cm2. The cultures with low proliferation rate demonstrated senescence-associated features and low frequency of clonogenic multipotent cells. At seeding density 100 cells/ cm2 cultures maintained high proliferation rate, hypoxia enhanced this effect even further up to 17—28 in vitro population doublings. Some of the donor-specific alterations in cell sample properties could be corrected by changing of culturing strategies.

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About the authors

R. I Dmitrieva

Insitute of Molecular Biology and Genetics of the Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg

M. A Klukina

Insitute of Molecular Biology and Genetics of the Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg

I. R Minullina

Insitute of Molecular Biology and Genetics of the Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg

S. V Anisimov

Insitute of Molecular Biology and Genetics of the Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg

A. Yu Zaritskey

Institute of Haematology of the Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg

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