Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (9): 1882-1889.doi: 10.4103/1673-5374.306090

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Angiogenesis and nerve regeneration induced by local administration of plasmid pBud-coVEGF165-coFGF2 into the intact rat sciatic nerve

Ruslan Masgutov1, 2, *, Alina Zeinalova1, Alexey Bogov2, Galina Masgutova1, Ilnur Salafutdinov1, Ekaterina Garanina1, Valeriia Syromiatnikova1, Kamilla Idrisova1, Adelya Mullakhmetova1, Dina Andreeva1, Liliya Mukhametova1, Adilet Kadyrov3, Igor Pankov3, Albert Rizvanov1#br#   

  1. 1OpenLab “Gene and Cell Technologies”, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia; 2Republican Clinical Hospital, Kazan, Russia; 3Department of Traumatology and Orthopedics, Kazan State Medical Academy, Kazan, Russia
  • Online:2021-09-15 Published:2021-02-05
  • Contact: Ruslan Masgutov, MD, PhD, masgut@gmail.com.
  • Supported by:
    his study was supported by the Russian Government Program of Competitive Growth of Kazan Federal University; state assignment 20.5175.2017/6.7 of the Ministry of Education and Science of Russian Federation and Grant of the President of the Russian Federation for state support of the leading scientific schools of the Russian Federation. The work was also supported by the Russian Government Program of Competitive Growth of the Kazan Federal University (to AR); the Russian Foundation for Basic Research grant 18-54-45023 Ind_a (to IS and GM).

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Abstract: Vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) are well-known growth factors involved in the regeneration of various tissues and organs, including peripheral nerve system. In the present study, we elucidated the local and systemic effects of plasmid construct рBud-coVEGF165-coFGF2 injected into the epineurium of intact rat sciatic nerve. Results of histological examination of sciatic nerve and multiplex immunoassays of serum showed the absence of immunogenicity and biosafety of plasmid рBud-coVEGF165-coFGF2. Moreover, local administration of plasmid DNA construct resulted in significantly decreased levels of pro-inflammatory cytokines in the peripheral blood, including tumor necrosis factor α (TNFα) and interleukin-12, and significantly increased levels of cytokines and chemokines including Regulated upon Activation, Normal T Cell Expressed and Presumably Secrete (RANTES), epidermal growth factor, interleukin-2, and monocyte chemoattractant protein 1. These changes in the peripheral blood on day 7 after injection of plasmid construct рBud-coVEGF165-coFGF2 show that the plasmid construct has systemic effects and may modulate immune response. At the same time, reverse transcription-polymerase chain reaction revealed transient expression of coFGF2, coVEGF165, ratFGF2 and ratVEGFA with direct transport of transcripts from distal part to proximal part of the sciatic nerve.  Immunohistochemical staining revealed prolonged presence of VEGFA in sciatic nerve till 14 days post-injection. These findings suggest that local administration of plasmid construct рBud-coVEGF165-coFGF2 at a concentration of 30 ng/µL results in the formation of pro-angiogenic stimuli and, and the plasmid construct, used as a drug for gene therapy, might potentially facilitate regeneration of the sciatic nerve. The study was approved by the Animal Ethics Committee of Kazan Federal University, procedures were approved by the Local Ethics Committee (approval No. 5) on May 27, 2014.

Key words: chemokines, cytokines, fibroblast growth factor, gene therapy, growth factors, peripheral nerve system, sciatic nerve regeneration, vascular endothelial growth factor