Novosti
Khirurgii
This journal is
indexed in Scopus



Year 2015 Vol. 23 No 4

SCIENTIFIC PUBLICATIONS
EXPERIMENTAL SURGERY

DOI: http://dx.doi.org/10.18484/2305-0047.2015.4.365   |  

B. S. SUKOVATYKH, A.Y. ORLOVA, E.B. ARTYUSHKOVA, M.Y. GORDOV, K.Y. VEDENEV

THE EFFECTIVENESS OF MONONUCLEAR FRACTION OF AUTOLOGOUS BONE MARROW IN TREATMENT OF EXPERIMENTAL CRITICAL LIMB ISCHEMIA

SBEE HPE "Kursk State Medical University"
The Russian Federation

Objectives. To develop an experimental model of critical limb ischemia for the further study of the effectiveness of the mononuclear fraction of autologous bone marrow in the treatment of critical limb ischemia.
Methods. The results of the application of the mononuclear fraction of autologous bone marrow in rats (Wistar) divided into four groups: intact, control, comparison and experimental have been analyzed. The intact group included 10 rats, the other groups – 30 animals in each. In all rats, except for the intact one, critical limb ischemia was created by excision of the main vessel, including the femoral artery, the popliteal artery and the initial segments of the leg arteries. Mononuclear fraction of autologous bone marrow from the femur contralateral limb of the rat in a volume of 200 μL was injected into the ischemic limb in the experimental group (every animal was given a 100 μL injection at two different injection sites: 1) directly below the inguinal ligament of the tissue in the area of the anatomical location of collaterals of the internal iliac artery; 2) intramuscularly in the gastrocnemius muscle of the anterior-lateral surface of the middle third of the tibia. In the control group the fraction was injected into the ischemic limb by infiltration at six different sites. In the control group the animals received no treatment. The treatment effectiveness was assessed by the dynamics of the microcirculation level by the 10th, 21st and 28th days by laser Doppler flowmetry.
Results. Assessment of the microcirculation in animals with experimental limb ischemia after treatment according to the original method in the experimental group with the compared group showed the increase in blood flow by the 10th days at the hip level by 1,5 folds, at leg – by 1,1 folds, by the 21st days at the level of the femur and tibia – by 1,4 folds and by the 28th days at the femur and tibia – by 1,2 folds.
Conclusion. The proposed method of treatment proven to be pathogenetically justified and effective.

Keywords: peripheral arterial disease, ischemia model, microcirculation level, model of the hind limb ischemia, therapeutic angiogenesis, bone marrow, mononuclear cells
p. 365-371 of the original issue
References
  1. Kuznetsov MR, Koshkin VM, Karalkin AV. Rannie reokkliuzii u bol'nykh obliteriruiushchim aterosklerozom [Early reocclusion in patients with atherosclerosis obliterans]. Iaroslavl'. Niuans. Meditsina, 2007. 176 p.
  2. Barsenev AV. Autogennaia transplantatsiia kletok pri ishemii konechnostei v klinike [Autologous transplantation of cells in ischemic limbs at the clinic]. Klet Transpl. 2005 Sen;I(1):40-43.
  3. Lawall H, Bramlage P, Amann B.Stem cell and progenitor cell therapy in peripheral artery disease. A critical appraisal. Thromb Haemost. 2010 Apr;103(4):696-709. doi: 10.1160/TH09-10-0688.
  4. Armstrong L, Lako M, Buckley N, Lappin TR, Murphy MJ, Nolta JA, Pittenger M, Stojkovic M. Editorial: Our top 10 developments in stem cell biology over the last 30 years. Stem Cells. 2012 Jan;30(1):2-9. doi: 10.1002/stem.1007.
  5. Walter DH, Krankenberg H, Balzer JO, Kalka C, Baumgartner I, Schlüter M, Tonn T, Seeger F, Dimmeler S, Lindhoff-Last E, Zeiher AM. Intraarterial administration of bone marrow mononuclear cells in patients with critical limb ischemia: a randomized-start, placebo-controlled pilot trial (PROVASA). Circ Cardiovasc Interv. 2011 Feb 1;4(1):26-37. doi: 10.1161/circinterventions.110.958348.
  6. Powell RJ, Comerota AJ, Berceli SA, Guzman R, Henry TD, Tzeng E, Velazquez O, Marston WA, Bartel RL, Longcore A, Stern T, Watling S. Interim analysis results from the RESTORE-CLI, a randomized, double-blind multicenter phase II trial comparing expanded autologous bone marrow-derived tissue repair cells and placebo in patients with critical limb ischemia. J Vasc Surg. 2011 Oct;54(4):1032-41. doi: 10.1016/j.jvs.2011.04.006.
  7. Nozdrachev AD, Poliakov EL. Anatomiia krysy (Laboratornye zhivotnye) [Anatomy of rats (Laboratory animals)]. Saint-Petersburg, RF: Lan', 2001. 464 p.
  8. Waterman RS, Betancourt AM. Treating Chronic Pain with Mesenchymal Stem Cells: A Therapeutic Approach Worthy of Continued Investigation. J Stem Cell Res Ther. 2011. S2:001. doi: 10.4172/2157-7633.S2-001
  9. Sukovatykh AIu, Orlova MV, Pokrovskii EB, Artiushkova BS. Sposob lecheniia khronicheskikh obliteriruiushchikh zabolevanii arterii nizhnikh konechnostei [The method of treatment of chronic obliterating diseases of arteries of the lower extremities]: patent RF A61K 35/14, A61R 9/10, A61M 5/00 / zaiavitel' Kurskii Gos Med Universitet № 2392948. 2010 06. 27. Otkrytiia Izobret. 2010;(18):35.
  10. Boyum A. Separation of leukocytes from blood and bone marrow Scand J Clin Lab Investig.1998;(21)Suppl.97:1-9
  11. Tidball JG, Villalta SA. Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol Regul Integr Comp Physiol. 2010 May;298(5):R1173-87. doi: 10.1152/ajpregu.00735.2009.
  12. Belch J, Hiatt WR, Baumgartner I, Driver IV, Nikol S, Norgren L, Van Belle E. Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limb ischaemia. Lancet. 2011 Jun 4;377(9781):1929-37. doi: 10.1016/S0140-6736(11)60394-2.
  13. Tidball JG, Villalta SA. Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol Regul Integr Comp Physiol. 2010 May;298(5):R1173-87. doi: 10.1152/ajpregu.00735.2009.
  14. Shevchenko IuL. Mediko-biologicheskie i fiziologicheskie osnovy kletochnykh tekhnologii v serdechno-sosudistoi khirurgii [Medico-biological and physiological basis of cellular technologies in cardiovascular surgery]. Saint-Petersburg, RF: Nauka. 2006. 288 p.
  15. Fadini GP, Agostini C, Avogaro A. Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis. 2010 Mar;209(1):10-17. doi: 10.1016/j.atherosclerosis.2009.08.033.
Address for correspondence:
305041 Russian Federation,
Kursk, ul. K.Marksa, d. 3,
GBOU VPO "Kurskiy gosudarstvennyiy meditsinskiy universitet",
kafedra obschey khirurgii,
tel. office 8 4712 52-98-62,
e-mail: SukovatykhBS@kursksmu.net,
Sukovatykh Boris Semenovich
Information about the authors:
Sukovatykh B.S. MD, professor, a head of the general surgery chair of SBEE HPE "Kursk State Medical University".
Orlova A.Y. PhD, an assistant of the general surgery chair of SBEE HPE "Kursk State Medical University".
Artyushkova E.B. MD, a director of SRI of Ecological Medicine of SBEE HPE "Kursk State Medical University".
Gordov M.Y. A competitor of the general surgery chair of SBEE HPE "Kursk State Medical University".
Vedenev K.Y. A 3-year student of the medical faculty of SBEE HPE "Kursk State Medical University".
Contacts | ©Vitebsk State Medical University, 2007