Application of genetically modified umbilical cord blood cells and direct gene therapy for treatment of skin wounds in rats



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Abstract

There were proposed several methods for stimulation of skin wound repair over the last few decades. The most perspective among them are gene and stem cell therapy. In our experiments we combined both approaches by application of human cord blood mononuclear cells (hUCB-MC) transfected with pBud-VEGF165-FGF2 plasmid to enhance healing of full thickness skin wounds in rats. Dual expression cassette plasmid pBud-VEGF165-FGF2 encodes both VEGF and FGF2 therapeutic genes, expressing pro-angiogenic growth factors. Our results showed that in 2 weeks after transplantation some transplanted cells still retain expression of stem cell and hematopoietic markers C-kit and CD34. Other transplanted cells could be found among keratinocytes, hair follicle cells, endothelial cells and in derma. Study of PCNA expression revealed that application of transfected cells terminate proliferative processes in regenerating wound earlier then application of untransfected cells.

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About the authors

I. M Gazizov

Kazan (Volga region) Federal University; Kazan State Medical University

I. I Salafutdinov

Kazan (Volga region) Federal University

M. O Mavlikeev

Kazan (Volga region) Federal University

F. V Bashirov

Kazan State Medical University

R. R Islamov

Kazan State Medical University

A. A Rizvanov

Kazan (Volga region) Federal University

A. P Kiassov

Kazan (Volga region) Federal University

References

  1. Берлин Л.Б. Морфология кожи после ожогов и свободной пересадки. Л.: Медицина, 1966: 222.
  2. Niemann C., Watt F.M. Designer skin: lineage commitment in postnatal epidermis. Trends Cell Biol. 2002; 12 (4); 185-92.
  3. Singer A.J., Clark R.A. Cutaneous wound healing. N. Engl. J. Med. 1999; 341 (10): 738-46.
  4. Wu Y., Chen L., Scott P.G., Tredget E.E. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells. 2007; 25 (10): 2648-59.
  5. Tolar J., Blazar B.R., Wagner J.E. Concise Review: Transplantation of Human Hematopoietic Cells for Extracellular Matrix Protein Deficiency in Epidermolysis Bullosa. Stem Cells. 2011; 29: 900-6.
  6. Fathke C., Wilson L., Hutter J. et al. Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair. Stem Cells 2004; 22 (5): 812-22.
  7. Kamolz L.P., Kolbus A., Wick N. et al. Cultured human epithelium: human umbilical cord blood stem cells differentiate into keratino-cytes under in vitro conditions. Burns 2006; 32 (1): 16-9.
  8. Kim W.S., Park B.S., Sung J.H. et al. Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts. J. Dermatol. Sci. 2007; 48 (1): 15-24.
  9. Roh C., Lyle S. Cutaneous stem cells and wound healing. Pedi-atr. Res. 2006; 59 (4, Pt. 2): 100R-3R.
  10. Oshima H., Rochat A., Kedzia C. et al. Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 2001; 104 (2): 233-45.
  11. Sprugel K.H., McPherson J.M., Clowes A.W., Ross R. Effects of growth factors in vivo. I. Cell ingrowth into porous subcutaneous chambers. Am. J. Pathol. 1987; 129 (3): 601-13.
  12. Lynch S.E., Nixon J.C., Colvin R.B., Antoniades H.N. Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. PNAS USA 1987; 84 (21): 7696-700.
  13. Jeschke M.G., Klein D. Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene. Gene Ther. 2004; 11 (10): 847-55.
  14. Mathor M.B., Ferrari G., Dellambra E. et al. Clonal analysis of stably transduced human epidermal stem cells in culture. PNAS USA 1996; 93 (19): 10371-6.
  15. Hachiya A., Sriwiriyanont P., Patel A. et al. Gene transfer in human skin with different pseudotyped HIV-based vectors. Gene Ther. 2007; 14 (8): 648-56.
  16. Pereira C.T. et al. Scar trek: follicular frontiers in skin replacement therapy. Genet. Mol. Res. 2007; 6 (1): 243-9.
  17. Rizvanov A.A., Kiyasov A.P., Gazizov I.M. et al. Human umbilical cord blood cells transfected with VEGF, L1CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neuro-trophic factors to support neuro-genesis - a novel approach in stem cell therapy. Neurochemistry International 2008; 53: 389394. 18. Rizvanov A.A., Guseva D.S., Salafutdinov I.I. et al. Genetically modified human umbilical cord blood cells expressing vascular endothelial growth factor and fibroblast growth factor 2 differentiate into glial cells after transplantation into amyotrophic lateral sclerosis transgenic mice. Exp. Biol. Med. (Maywood) 2011; 236 (1): 91-8.
  18. Харин Г.М. Использование современных технологий в изучении посттравматической регенерации кожи. ПЭМ 2004; 16 (4): 11-3.
  19. Плотников М.В., Ризванов А.А., Масгутов Р.Ф. и др. Первые результаты клинического применения прямой генной терапии VEGF и bFGF при лечении пациентов с хронической ишемией нижних конечностей. Практическая медицина 2013; 2 (1-2): 123-5.
  20. Муллин Р.И., Масгутов Р.Ф., Салафутдинов И.И. Комбинированное лечение трофической язвы пяточной области с использованием вакуум-терапии в сочетании с прямой генной терапией: клинический случай. Клеточная трансплантология и тканевая инженерия 2013; 8 (3): 125-8.

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