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JMBS 2016, 1(2): 160–164
https://doi.org/10.26693/jmbs01.02.160
Medicine

Stimulation of Neovasculogenesis as a Treatment of Chronic Obliterating Diseases of Arteries of Lower Extremities

Popandopulo A., Savchuk M., Bushe V., Kavelina A., Popivnenko F.
Abstract

Recent scientific studies have confirmed a high potential of application of cellular technologies for formation of collateral blood vessels in ischemic limbs by stimulating angiogenesis. Currently, cellular mechanisms and sources of angiogenesis mainly identified, and there are a variety of growth factors that stimulate the development of new blood vessels. Cell therapy is a safe and effective complementary method that improves blood circulation in the limb ischemia. The data obtained from experimental and clinical studies, allow us to recommend the application of cellular technologies to stimulate neovaskulogenesis in treatment of the chronic obliterating diseases of lower limb arteries. A differential approach of using cellular technology is possible, depending on the etiology of the disease and the presence of comorbidities (diabetes, etc.). It should be noted that if comorbidities are present, platelet rich plasma therapy is impossible. There are a lot of studies which postulate of vascular endothelium, platelet, fibrinolysis and hematopexis malfunctions in case of diabetes. The most important factors causing diabetic angiopathy are increased platelet activity and decreased antitrombogenic properies of vessel wall. That factors result in intravascular platelet clumping, adhesion of platelets to vessel wall and, as a result, trombogenesis. In this case it makes sense to use another cell types for angiogenesis stimulation. The angiogenesis by local intramuscular injections of bone marrow-derived autologous peripheral blood mononuclear cells or granulocyte macrophage colony stimulating factor-mobilized peripheral blood mononuclear cells is indicated for treatment of limb ischemia patients. According to the data of the pre-clinical studies, bone marrow-derived autologous peripheral blood mononuclear cells injections in ischemia affected area lead to the measurable increase of the capillary density in comparison with control. Development and application of modern therapy methods for treatment of chronic limb ischemia allows significantly improve of treatment outcome and life quality. Success in this regard admits to rely on perspectivity of cell technologies in chronic limb ischemia treatment. However, the application of neoangiogenesis in the ischemic tissues as new an original direction demand on long-term and prospective studies with unbiased estimate of positive and negative results.

Keywords: angiogenesis, neovaskulogenesis, lower limb ischemia

Full text: PDF (Rus) 218K

References
  1. Sukovatyih BS, Orlova AYu, Artyushkova EB, i dr. Vliyanie plazmyi, obogaschennoy trombotsitami, i preparata «Mielopid» na techenie ostroy i hronicheskoy ishemii nizhnih konechnostey (eksperimentalno-klinicheskoe issledovanie). Novosti hirurgii. 2012; 20 (2): 41-8.
  2. Dragunov AG, Aleksandrov YuV, Hripunov SA. Primenenie vnutritkanevogo vvedeniya autoplazmyi, obogaschennoy trombotsitami pri lechenii ishemii nizhnih konechnostey. Angiologiya i sosudistaya hirurgiya. 2008; 14 (4): 17-9.
  3. Dragunov AG. Kliniko-eksperimentalnoe obosnovanie stimulyatsii angiogeneza metodom vvedeniya v tkani goleni i stopyi autoplazmyi, obogaschennoy trombotsitami, dlya lecheniya hronicheskih obliteriruyuschih zabolevaniy arteriy nizhnih konechnostey: Abstr. PhDr. (Med.). Nizhniy Novgorod; 2010. 103 s.
  4. Konenkov VI, Klimontov VV. Angiogenez i vaskulogenez pri saharnom diabete: novyie kontseptsii patogeneza i lecheniya sosudistyih oslozhneniy. Saharnyiy diabet. 2012; 4: 17-27.
  5. Nikonenko OS. Efektivnist PRP-terapiyi u hvorih z oklyuzieyu stegnovo-pidkolinno-gomilkovogo segmentu. Naukoviy visnik Uzhgorodskogo universitetu. SerIya «Meditsina». 2012; 2 (44): 83-5.
  6. Nikonenko AS, Voloshin AN, Makarchenko YuI. Harakteristika morfologicheskih izmeneniy myishechnoy tkani goleni posle PRP-terapii. Visnik sertsevo-sudinnoyi hirurgiyi. 2014; 22: 211-4.
  7. Patent RU 2529410 C1, A61V 17/00, A61M 25/00. Sposob hirurgicheskogo lecheniya hronicheskogo lecheniya hronicheskoy ishemii nizhnih konechnostey, obuslovlennoy distalnyim tipom porazheniya sosudov. Korovin AYa, Bazlov SB, Porodenko EE; zayavitel i patentoobladatel Gosudarstvennoe Byudzhetnoe Obrazovatelnoe Uchrezhdenie Vyisshego Professionalnogo Obrazovaniya «Kubanskiy gosudarstvennyiy meditsinskiy universitet» Minzdrava Rossii. Zayavl 02.04.2013; opubl 27.09.2014, Byul 27.
  8. Plotnikov MV, Maksimov AV. Lechenie zabolevaniy perifericheskih arteriy s ispolzovaniem progenitornyih kletok. Prakticheskaya meditsina. 2014; 2 (80): 118-22.
  9. Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care. 2005; 28 (9): 2155-60. https://www.ncbi.nlm.nih.gov/pubmed/16123483 https://doi.org/10.2337/diacare.28.9.2155
  10. Ismail AM, Abdou SM, Aly HA, et al. Autologous transplantation of CD34+ bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia. Cytotechnology. 2014: 1–11.
  11. Lu D, Chen B, Liang Z, Deng W, Jiang Y, Li S, Xu J, Wu Q, Zhang Z, Xie B, Chen S. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract. 2011; 92 (Issue 1): 26–36. https://www.ncbi.nlm.nih.gov/pubmed/21216483. https://doi.org/10.1016/j.diabres.2010.12.010
  12. Hirsch AT. The global pandemic of peripheral artery disease. The Lancet. 2013; 382 (Issue 9901): 1312-4. https://doi.org/10.1016/S0140-6736(13)61576-7
  13. Iba O, Matsubara H, Nozawa Y, Fujiyama S, Amano K, Mori Y, Kojima H, Iwasaka T. Angiogenesis is by implication of peripheral blood mononuclear cells and platelets into ischemic limbs. Circ. 2002; 106: 2019-25. https://www.ncbi.nlm.nih.gov/pubmed/12370229 https://doi.org/10.1161/01.CIR.0000031332.45480.79
  14. Lawall H, Bramlage P, Amann B. Stem cell and progenitor cell therapy in peripheral artery disease. A critical appraisal. Thromb Haemost. 2010; 103 (4): 696-709. https://www.ncbi.nlm.nih.gov/pubmed/20174766. https://doi.org/10.1160/TH09-10-0688
  15. Madeddu P. Therapeutic angiogenesis and vasculogenesis for tissue regeneration. Experimental Physiology. 2005; 90 (3): 315-26. https://www.ncbi.nlm.nih.gov/pubmed/15778410. https://doi.org/10.1113/expphysiol.2004.028571
  16. Alaa Ismail, Hussein E, Sabbour A, et al. Treatment with autologous bone marrow mononuclear cells in patients. J Transplant Technol Res. 2012; 2 (Issue 2): S1-S3.