Effect of Bone Marrow Cell Intramyocardial Autotransplantation upon Perfusion of Ischemic Myocardium in Experiment

Cover Page


Cite item

Full Text

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

Abstract

The article presents results of investigation into comparative evaluation of the effects of autologous intramyocardial transplantation of multipotent mesenchymal stromal cells taken from bone marrow and of mononuclear bone marrow fraction upon perfusion of a rabbit ischemic myocardium. Myocardial infarction was simulated by means of ligation of the left coronary artery descending branch. Myocardium perfusion was evaluated with single-photon emission computed tomography with the application of a radiopharmaceutic drug [RPD] 99mTc-tetraphosmine [Myoview] prior to the simulation of myocardial infarction and in 10 days, 1.5 months, 3,6 and 12 months. The animals were divided into three groups: the 1st group [n=12] included animals whom multipotent mesenchymal bone marrow stromal cells were introduced into the ischemic zone [2Ч106]; in the 2nd group [n=14] mononuclear bone marrow fraction was introduced [2Ч106]; and the 3rd group [n=15, control] where growth medium was used.

In all the animals of the1st and 2nd groups, considerable improvement of perfusion was observed in 1.5 months following the operation. Mean values of the RPD accumulation were 0.92±0.03 and 0.89±0.031 respectively. In the control group this value was 0.62±0.02. By the third month following the operation complete normalizing of perfusion occurred in the experimental groups with the RPD accumulation level of 1.00±0.02 and 0.98±0.01, whereas this parameter did not increase in the control group and was 0.61±0.01. On the 10th day after the operation the perfusion evenness parameters in pathologic and reference zones were as follows: in the 1st group - 2.7±0.2 and 2.1±0.2; in the 2nd group - 2.6±0.2 and 1.8±0.3; in the controls - 2.8±0.3 and 2.1±0.1. In 3 months after the infarction simulation these values did not significantly differ in the 1st and 2nd groups [1.9±0.2; 2.0±0.1 and 2.1±0.1; 2.0±0.2]; in the controls the unevenness of perfusion increased considerably and amounted up to 3.5±0.2 in the damaged segment as compared with 2.0±0.1 in the intact one.

Full Text

Restricted Access

About the authors

A. A. Matyukov

Saint-Petersburg State Pavlov Medical University

Author for correspondence.
Email: redaktor@celltranspl.ru
Russian Federation, Saint-Petersburg

References

  1. Государственный доклад о состоянии здоровья населения Российской Федерации в 2001 году. Здравоохранение Российской Федерации 2000; 2: 7-22.
  2. Беленков Ю.Н., Мареев В.Ю., Агеев Ф.Т. Медикаментозные пути улучшения прогноза больных хронической сердечной недостаточностью. 1997; М.: Инсайт: 77.
  3. Репин В.С. Трансплантация клеток: новые реальности в медицине. Бюлл. эксперим. биол. и мед. 1998; 126 (приложение 1): 14-28.
  4. Chachques J.S., Salanson-Lajos C., Lajos C. et al. Cellular cardiomyoplasty for myocardial regeneration. Asian Cardiovasc. Thorac. Ann. 2005; 13(3): 287-96.
  5. Limbourg F.P., Ringes-Lichtenberg S., Schaefer A. et al. Haematopoietic stem cells improve cardiac function after infarction without permanent cardiac engraftment. Eur. J. Heart Fail. 2005; 7(5): 722-9.
  6. Murohara T., Ikeda H., Duan J. et al. Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J. Clin. Invest. 2000; 105: 1527-36.
  7. Asahara T., Takahashi T., Masuda H. et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999; 18: 3964-72.
  8. КаЩіеіе D.G., Sotiropoulou P.A., Karvouni E. et al. Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc. Interv. 2005; 65(3): 321-9.
  9. Shintani S., Murohara T., Ikeda H. et al. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circ. 2001; 103: 897-5.
  10. Zhang S. Long-term effects of bone marrow mononuclear cell transplantation on left ventricular function and remodeling in rats. Life Sci. 2004; 74(23): 2853-64.
  11. Al-Khaldi A., Eliopoulos N., Martineau D. et al. Therapeutic angiogenesis using autologous bone marrow stromal cells. Ann. Thorac. Surg. 2003; 75(1): 204-9.
  12. Tang Y.L. Autologous mesenchymal stem cells for post-ischemic myocardial repair. Methods Mol. Med. 2005; 112: 183-92.
  13. Непомнящих Л.М. Морфология адаптивных реакций миокарда при экстремальных экологических воздействиях. Вестн. РАМН 1997; 3: 43-53.
  14. Полежаев Л.В. Состояние проблемы регенерации мышцы сердца. Усп. совр. биол. 1995; 115: 198-212.
  15. Matsunari I., Kanayama S., Yoneyama T. et. al. Myocardial distribution of 18F-FDG and 99mTc-sestamibi on dual-isotope simultaneous acquisition SPET compared with PET. E. J. of Nuclear Medicine 2002; 29(10): 1357-64.
  16. Фриденштейн А.Я. Стволовые остеогенные клетки костного мозга. Онтогенез 1991; 2: 189-97.
  17. Orlic D., Kajstura J., Chimenti S. et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410: 701-5.
  18. Tang Y.L., Zhao Q., Qin X. et al. Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann. Thorac. Surg. 2005; 80(1): 229-36; discussion 236-7.
  19. Vandervelde S., Luyn M.J., Tio R.A. et al. Signaling factors in stem cell-mediated repair of infarcted myocardium. Mol. Cell Cardiol. 2005; 39(2): 363-76.
  20. Azarnoush K., Maurel A., Sebbah L. et al. Enhancement of the functional benefits of skeletal myoblast transplantation by means of coadministration of hypoxiainducible factor 1alpha. J. Thorac. Cardiovasc. Surg. 2005; 130(1):173-9.
  21. Archundia A., Aceves J.L., Lopez-Hernandez M. et al. Direct cardiac injection of G-CSF mobilized bone-marrow stem-cells improves ventricular function in old myocardial infarction. Life Sci. 2005; 78(3): 279-83.
  22. Matsumoto R., Omura T., Yoshiyama M. et al. Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction. Arterioscler. Thromb. Vasc. Biol. 2005; 25(6): 1168-73.
  23. Yoon J., Min B.G., Kim Y.H. Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model. Acta Cardiol. 2005; 60(3): 277-84.
  24. Takakura N., Watanabe T., Suenobu S. et. al. A Role for Hematopoietic Stem Cells in Promoting Angiogenesis. Circ. 1999; 53(11): 452-68.
  25. Kobayashi T., Hamano K., Li T.S. et al. Angiogenesis induced by the injection of peripheral leukocytes and platelets. Surg. Res. 2002; 103: 279-86.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig.1. Doping of the anterior descending branch of the left coronary artery

Download (83KB)
Indexing metadata
3. Fig. 2. Introduction of cells into the ischemic zone of the left ventricular myocardium

Download (80KB)
Indexing metadata
4. Fig. 3. Perfusion tomoscintigraphy of rabbit myocardium

Download (8KB)
Indexing metadata
5. Fig. 4. Culture of multipotent mesenchymal stromal cells obtained from rabbit bone marrow, 21st day of cultivation, azur II staining. Magnification x20

Download (107KB)
Indexing metadata
6. Fig. 5. Fluorescence microscopy of rabbit myocardium preparation after enzymatic dissociation. The arrows indicate the nuclei of transplanted cells labeled with Hoechst fluorochrome. Magnification x400

Download (10KB)
Indexing metadata
7. Fig. 6. Perfusion tomoscintigrams of rabbit myocardium: the first group is transplantation of multipotent mesenchymal stromal bone marrow cells; the second group is transplantation of nucleated bone marrow cells; the third group is control

Download (60KB)
Indexing metadata
8. Fig. 7. Uniformity of RFP distribution after transplantation of multipotent mesenchymal stromal cells (the first group) and the nucleated fraction (the second group) of bone marrow in the pathological (indicated in red) and reference (indicated in blue) zones

Download (46KB)
Indexing metadata
9. Fig. 7_2

Download (92KB)
Indexing metadata

Copyright (c) 2006 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: 

This website uses cookies

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

About Cookies