Biological activity comparative evaluation of the gene-activated bone substitutes made of octacalcium PHOSPHATE AND PLASMID DNA CARRYING VEGF AND SDF GENES: PART 1 - IN VITRO

  • Authors: Bozo I.Y1,2,3,4,5, Maiorova K.S6, Drobyshev A.Y7, Rozhkov S.I7, Volozhin G.A7, Eremin I.I8, Komlev V.S9,10, Smirnov I.V9,10, Rizvanov A.A11, Isaev A.A12, Popov V.K10, Deev R.V13,2,10
  • Affiliations:
    1. Federal Research Center “Crystallography and photonics” RAS
    2. Human Stem Cells Institute
    3. A.I. Evdokimov Moscow State University of Medicine and Dentistry
    4. State Research Center “A.I. Burnazyan Federal Medical Biophysical Center” of the FMBA of Russia
    6. Institute of General Genetics of the RAS.
    7. A.I. Evdokimov Moscow State University of Medicine and Dentistry.
    8. Central Clinical Hospital with Outpatient Health Center of the Business Administration for the President of the Russian Federation.
    9. A.A. Baykov Institute of Metallurgy and Material Science of the RAS
    10. Federal Research Center “Crystallography and photonics” RAS.
    11. Kazan (Volga region) Federal University.
    12. Human Stem Cells Institute.
    13. I.P.Pavlov Ryazan State Medical University
  • Issue: Vol 11, No 4 (2016)
  • Pages: 34-42
  • Section: Articles
  • URL: https://genescells.ru/2313-1829/article/view/120571
  • DOI: https://doi.org/10.23868/gc120571
  • ID: 120571


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Abstract

High need for effective bone substitutes and drawbacks of the materials approved for clinical use determine the increasing activity of biomedical research in this area. We have developed gene-activated bone substitutes consisting of a scaffold based on octacalcium phosphate (OCP) and one of the two variants of plasmid DNA carrying either a gene for vascular endothelial growth factor (VEGF) or two genes encoding VEGF and stromal derived factor-1а (SDF-1a). The aim of the study was to evaluate the cytotoxicity of the gene-activated materials and their components, as well as biological activity in vitro. We found that both OCP and gene-activated bone substitutes did not have any cytotoxicity, but reduced the proliferative activity of human bone marrow-derived multipotent mesenchymal stromal cells: material with doublegene construct decreased cell culture doubling rate of 24.3% more compared with the material carrying plasmid DNA encoding only VEGF. Both gene-activated materials led to an increase in therapeutic genes mRNA levels, but the material with double-gene system enhanced VEGF protein production greater. Thus, the gene-activated bone substitutes characterized by the absence of cytotoxic properties and possessed a specific activity increasing expression of the therapeutic genes. However, further studies are needed to detail the identified characteristics and assess the feasibility of the defined biological action in vivo. свойств и обладали специфической активностью в виде увеличения экспрессии терапевтических генов. Однако дальнейшие исследования необходимы для детализации выявленных особенностей и оценки реализуемости биологического действия in vivo.

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About the authors

I. Y Bozo

Federal Research Center “Crystallography and photonics” RAS; Human Stem Cells Institute;A.I. Evdokimov Moscow State University of Medicine and Dentistry;State Research Center “A.I. Burnazyan Federal Medical Biophysical Center” of the FMBA of Russia;

Moscow, Russia

K. S Maiorova

Institute of General Genetics of the RAS.

Moscow, Russia

A. Y Drobyshev

A.I. Evdokimov Moscow State University of Medicine and Dentistry.

Moscow, Russia

S. I Rozhkov

A.I. Evdokimov Moscow State University of Medicine and Dentistry.

Moscow, Russia

G. A Volozhin

A.I. Evdokimov Moscow State University of Medicine and Dentistry.

Moscow, Russia

I. I Eremin

Central Clinical Hospital with Outpatient Health Center of the Business Administration for the President of the Russian Federation.

Moscow, Russia

V. S Komlev

A.A. Baykov Institute of Metallurgy and Material Science of the RAS; Federal Research Center “Crystallography and photonics” RAS.

I. V Smirnov

A.A. Baykov Institute of Metallurgy and Material Science of the RAS;Federal Research Center “Crystallography and photonics” RAS.

Moscow, Russia

A. A Rizvanov

Kazan (Volga region) Federal University.

Kazan, Russia

A. A Isaev

Human Stem Cells Institute.

Moscow, Russia

V. K Popov

Federal Research Center “Crystallography and photonics” RAS.

Moscow, Russia

R. V Deev

I.P.Pavlov Ryazan State Medical University;Human Stem Cells Institute; Federal Research Center “Crystallography and photonics” RAS.

Ryazan,Moscow,Russia.

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