EFFECTS OF TRANSPLANTATION OF HUMAN UMBILICAL CORD BLOOD MONONUCLEAR CELLS, EXPRESSING VEGF AND FGF2 GENES, INTO THE AREA OF SPINAL CORD TRAUMATIC LESION



Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Effects of immediate single transplantation of human umbilical cord blood mononuclear cells (UCB-MC) transfected with recombinant vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF2) genes into the area of injury were studied on the model of rat spinal cord dosed contusion at TVIII level. UCB-MC transfected with EGFP-N2 plasmid were transplanted into the rats of the control group under similar conditions. The presence of EGFP- labeled cells were traced in white matter during 21 days after transplantation at a distance no less than 10 mm in rostral and caudal directions from the nearest point of the injection. By 30 days after the transplantation of UCB-MC transfected with pBud-VEGF-FGF2 plasmid, the cross-sectional area of sparing grey matter increased by more than 60% at a distance of 3 mm from the epicenter of injury. By that time, in the animals of this group, the number of perivascular cells expressing beta receptor of platelet-derived growth factor (PDGFβR) was increased by an average of 30% in the outer zones of white matter 1.5 cm from the injury epicenter. Delivery of the therapeutic genes VEGF and FGF2 to the damaged region and their expression in cell carriers stimulates vascularization and post-traumatic spinal cord regeneration.

References

  1. Лебедев С. В., Карасев А. В., Чехонин В. П. и др. Исследование эффективности трансплантации нейральных стволовых клеток человека крысам с травмой спинного мозга: применение функциональных нагрузочных тестов и метода ВВВ. Бюл. экспер. биол., 2010, т. 149, № 3, с. 355-360.
  2. Лебедев С. В., Тимофеев С. В., Жарков А. В. и др. Нагрузочные тесты и метод ВВВ при оценке двигательных нарушений после контузионной травмы спинного мозга. Бюл. экспер. биол., 2008, т. 145, № 10, с. 471-476.
  3. Салафутдинов И. И., Шафигуллина А. К., Ялвач М. Э. и др. Эффект одновременной экспрессии различных изоформ фактора роста эндотелия сосудов VEGF и основного фактора роста фибробластов FGF2 на пролиферацию эндотелиальных клеток пупочной вены человека HUVEC. Клеточная трансплантология и тканевая инженерия, 2010, т. 5, № 2, с. 62-57.
  4. Челышев Ю. А. и Викторов И. В. Клеточные технологии ремиелинизации при травме спинного мозга. Неврол. вестн. им. В. М. Бехтерева, 2009, № 1, с. 49-55.
  5. Bai L., Lennon D. P., Eaton V. et al. Human bone marrowderived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia. 2009, v. 57, № 11, p. 1192-1203.
  6. Betsholtz C., Lindblom P. and Gerhardt H. Role of pericytes in vascular morphogenesis. EXS, 2005, v. 94, p. 115-125.
  7. Han S. S., Liu Y., Tyler-Polsz C. et al. Transplantation of glialrestricted precursor cells into the adult spinal cord: survival, glialspecific differentiation, and preferential migration in white matter. Glia, 2004, v. 45, p. 1-16.
  8. Hellstrom M., Gerhardt H., Kalen M. et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J. Cell Biol., 2001, v. 153, p. 543-553.
  9. Jin L.H, Pennant W. A., Lee H. M. et al. Neural stem cells modified by a hypoxia-inducible VEGF gene expression system improve cell viability under hypoxic conditions and spinal cord injury. Spine, 2011, v. 36, № 11, p. 857-864.
  10. Khalatbary A. R. and Tiraihi T. Localization of bone marrow stromal cells in injured spinal cord treated by intravenous route depends on the hemorrhagic lesions in traumatized spinal tissues. Neurol. Res., 2007, v. 29, № 1, p. 21-26.
  11. Lindahl P., Johansson B., Leveen P. and Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B deficient mice. Science, 1997, v. 277, p. 242-245.
  12. Rizvanov A. A., Kiyasov A. P., Gaziziov I. M. et al. Human umbilical cord blood cells transfected with VEGF and L(1)CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neuro-trophic factors to support neuro-genesisa novel approach in stem cell therapy. Neurochem Int., 2008, v. 53, № 6-8, p. 389-394.
  13. Ronaghi M., Erceg S., Moreno-Manzano V. and Stojkovic M. Challenges of stem cell therapy for spinal cord injury: human embryonic stem cells, endogenous neural stem cells, or induced pluripotent stem cells? Stem Cells, 2010, v. 28, № 1, p. 93-99.
  14. Ronsyn M. W., Berneman Z. N., Van Tendeloo V. F. et al. Can cell therapy heal a spinal cord injury? Spinal Cord, 2008, v. 46, № 8, p. 532-539.
  15. Zhao Z. M., Li H. J., Lu S. H. et al. Intraspinal transplantation of CD34+ human umbilical cord blood cells after spinal cord hemisection injury improves functional recovery in adult rats. Cell Transplant., 2004, v. 13, № 2, p. 113-122.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2012 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: № 0110212 от 08.02.1993.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies