ANGIOGENESIS IN THE TISSUES AFTER THE INJECTION OF STROMAL STEM CELLS OF BONE MARROW ORIGIN CLOSE TO THROMBOSED VEIN IN AN EXPERIMENT

Abstract

The effects of the injection of autologous multipotent stromal stem cells of bone marrow origin (MSSCBM) (mesenchymal stem cells) with green fluorescent protein gene, additionally marked with DAPI nuclear stain, close to a thrombosed hindlimb vein, were studied by fluorescent microscopy in adult male Wag rats (n=214). The control groups consisted of intact rats (n=12), animals with venous thrombosis without the injection of MSSCBM (n=71) and rats that received paravasal injection of MSSCBM, but without preliminary modeling of venous thrombosis (n=72). It was found that MSSCBM participated in the development of granulation tissue at the site of surgical intervention performed during the modeling of thrombosis. The rapid development of granulation tissue at the site of surgical trauma may contribute to faster wound clearance from detritus, nonviable tissue and antigenic substances, early onset of tissue repair processes and rapid healing. Restoration of blood flow in the tissue region of a thrombosed vein began later than after the intravenous injection of MSSCBM.

Keywords

multipotent mesenchymal stem cells / venous thrombosis / thrombus recanalization / angiogenesis / blood flow restoration

References

[1] Майбородин И. В., Морозов В. В., Новикова Я. В. и др. Морфологические результаты введения стромальных стволовых клеток костномозгового происхождения в тромбированную вену в эксперименте // Морфология. 2012. Т. 142, вып. 4. С. 54-61.

[2] Майбородин И. В., Якимова Н. В., Матвеева В. А. и др. Морфологический анализ результатов введения аутологичных стволовых стромальных клеток костномозгового происхождения в рубец матки крыс // Морфология. 2010. Т. 138, вып. 6. С. 47-55.

[3] Шевченко Ю. Л., Стойко Ю. М., Лыткина М. И. Основы клинической флебологии. М.: Медицина, 2005.

[4] Carmeliet P., Luttun A. The emerging role of the bone marrow-derived stem cells in (therapeutic) angiogenesis // Thromb. Haemost. 2001. Vol. 86, № 1. P. 289-297.

[5] Chen Y. K., Jiang X. M., Gong J. P. Recombinant human granulocyte colony-stimulating factor enhanced the resolution of venous thrombi // J. Vasc. Surg. 2008. Vol. 47, № 5. P. 1058- 1065.

[6] Gu Y., Qi L., Zhang J. et al. Middle-term outcome of autologous bone marrow mononuclear cells transplantation for treatment of lower limb ischemia // Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009. Vol. 23, № 3. P. 341-344.

[7] Li X. Q., Meng Q. Y., Wu H. R. Effects of bone marrow-derived endothelial progenitor cell transplantation on vein microenvironment in a rat model of chronic thrombosis // Chin. Med. J. (Engl.). 2007. Vol. 120, № 24. P. 2245-2249.

[8] Maiborodin I., Yakimova N., Matveeva V. et al. Angiogenesis in rat uterine scar after introduction after autological mesenchymal stem cells of bone marrow origin // J. Biomed. Sci. Engineering. 2011. Vol. 4, № 3. P. 164-172.

[9] Meng Q. Y., Li X. Q., Yu X. B. et al. Transplantation of VEGF165gene-transfected endothelial progenitor cells in the treatment of chronic venous thrombosis in rats // Chin. Med. J. (Engl.). 2010. Vol. 123, № 4. P. 471-477.

[10] Modarai B., Burnand K. G., Humphries J. et al. The role of neovascularisation in the resolution of venous thrombus // Thromb. Haemost. 2005. Vol. 5. P. 801-809.

[11] Modarai B., Burnand K. G., Sawyer B., Smith A. Endothelial progenitor cells are recruited into resolving venous thrombi // Circulation. 2005. Vol. 111, № 20. P. 2645-2653.

[12] Modarai B., Humphries J., Burnand K. G. et al. Adenovirus-mediated VEGF gene therapy enhances venous thrombus recanalization and resolution // Arterioscler. Thromb. Vasc. Biol. 2008. Vol. 28, № 10. P. 1753-1759.

[13] Moldovan N. I., Asahara T. Role of blood mononuclear cells in recanalization and vascularization of thrombi: past, present, and future // Trends Cardiovasc. Med. 2003. Vol. 13, № 7. P. 265-269.

[14] Santo S. D., Tepper O. M., Ballmoos von M. W. et al. Cell-based therapy facilitates venous thrombus resolution // Thromb. Haemost. 2009. Vol. 101, № 3. P. 460-464.

[15] Shi Q., Rafii S., Wu M. H. et al. Evidence for circulating bone marrow-derived endothelial cells // Blood. 1998. Vol. 92, № 2. P. 362-367.

[16] Shi Q., Wu M. H., Hayashida N. et al. Proof of fallout endo thelialization of impervious Dacron grafts in the aorta and inferior vena cava of the dog // J. Vasc. Surg. 1994. Vol. 20, № 4. P. 546-557.

[17] Tong Z., Gu Y., Zhang J. et al. Changes of endothelial progenitor cells in rats after bone-marrow stimulation // Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2008. Vol. 22, № 10. P. 1218-1221.

[18] Wessler S., Reimer S. M., Sheps M. C. Biological assay of a thrombosis inducing activity in human serum // J. Appl. Physiol. 1959. Vol. 14. P. 943-946.

RIGHTS & PERMISSIONS

Eco-Vector