Effect of autologous mesenchymal stem cells induced by low level laser therapy on cardiogenesis in the infarcted area following myocardial infarction in rats

DOI: 10.4236/jbise.2013.68A1003   PDF   HTML   XML   3,715 Downloads   5,524 Views   Citations


In this study, we investigated the hypothesis that photobiostimulation by low-energy laser therapy (LLLT) applied to the bone marrow (BM) of myocardial infarcted rats may attenuate the scarring processes that follow myocardial infarction (MI). Wistar rats underwent experimental MI. LLLT (Ga-Al-As diode laser) was applied to the BM of the exposed tibia at different time intervals post-MI (4 hrs, 48 hrs and 5 days). Sham-operated infarcted rats served as control. Infarct size was significantly reduced (55%) in the laser-treated rats as compared to the control non-treated rats, at 2 weeks post-MI. A significant 3-fold increase was observed in the density of desmin immunopositive stained cells 14 days post-MI in the infarcted area of the laser-treated rats as compared to the non-laser-treated controls. The electron microscopy from the control infarcted rat hearts revealed a typical interphase area between the intact myocardium and the infarcted area, with conspicuous fibroblasts with collagen deposition dispersed among them. In rats that were laser treated (to BM), the interphase zone demonstrated cells with different intracellular structures. There was also a significant increase in the percentage of c-kit positive cells and macrophages in the circulating blood of the laser treated rats as compared to control non treated ones. In the majority of the cells clusters of myofibrils anchored to well-developed Z-lines and structures resembling the morphological characteristics of mature intact cardiomyocytes were evident. In conclusion, LLLT to the BM of rats post-MI induces cardiogenesis mainly at the borders of the infarcted area in the heart.

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Tuby, H. , Yaakobi, T. , Maltz, L. , Delarea, Y. , Sagi-Assif, O. and Oron, U. (2013) Effect of autologous mesenchymal stem cells induced by low level laser therapy on cardiogenesis in the infarcted area following myocardial infarction in rats. Journal of Biomedical Science and Engineering, 6, 24-31. doi: 10.4236/jbise.2013.68A1003.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Rumyantsev, P.P. (1977) Interrelations of the proliferation and differentiation processes during cardiac myogenesis and regeneration. International Review of Cytology, 51, 186-273. doi:10.1016/S0074-7696(08)60228-4
[2] Poss, K.D., Wilson, L.G. and Keating, M.T. (2002) Heart regeneration in zebrafish. Science, 298, 2188-2190. doi:10.1126/science.1077857
[3] Rumyantsev, P.P. (1973) Post-injury DNA synthesis, mitosis and ultrastructural reorganization of adult frog cardiac myocytes. An electron microscopic-autoradiographic study. Z Zellforsch Mikrosk Anat, 139, 431-50. doi:10.1007/BF00306596
[4] Barnett, P. and van den Hoff, M.J.B. (2011) Cardiac regeneration: Different cells same goal. Medical & Biological Engineering & Computing, 49, 723-732. doi:10.1007/s11517-011-0776-5
[5] Bollini, S., Smart. N. and Riley, P.R. (2011) Resident cardiac progenitor cells: At the heart of regeneration. Journal of Molecular and Cellular Cardiology, 50, 296-303. doi:10.1016/j.yjmcc.2010.07.006
[6] Choi, W.Y. and Poss, K.D. (2012) Cardiac regeneration. Current Topics in Developmental Biology, 100, 319-343. doi:10.1016/B978-0-12-387786-4.00010-5
[7] Laflamme, M.A. and Murry, C.E. (2011) Heart regeneration. Nature, 473, 326-335. doi:10.1038/nature10147
[8] Steinhauser, M.L. and Lee, R.T. (2011) Regeneration of the heart. EMBO Molecular Medicine, 3, 701-712. doi:10.1002/emmm.201100175
[9] Urbanek, K., Torella, D., Sheikh, F., De Angelis, A., Nurzynska, D., Silvestri, F., Beltrami, C.A., Bussani, R., Beltrami, A.P., Quaini, F., Bolli, R., Leri, A., Kajstura. J. and Anversa, P. (2005) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proceedings of the National Academy of Sciences of the USA, 102, 8692-8697. doi:10.1073/pnas.0500169102
[10] Bittner, R.E., Schofer, C., Weipoltshammer, K., Ivanova, S., Streubel, B., Hauser, E., Freilinger, M., Hoger, H., Elbe-Bürger, A. and Wachtler, F. (1999) Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anatomy and Embryology, 199, 391-396. doi:10.1007/s004290050237
[11] Jackson, K.A., Majka, S.M., Wand, H., Pocius, J., Hartley, C.J., Majesky, M.W., Entman, M.L., Michael, L.H., Hirschi, K.K. and Goodell, M.A. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. The Journal of Clinical Investigation, 107, 1395-1402. doi:10.1172/JCI12150
[12] Pfister, O., Mouquet, F., Jain, M., Summer, R., Helmes, M., Fine, A., Colucci, W.S. and Liao, R. (2005) CD3 but not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circulation Research, 97, 52-61. doi:10.1161/01.RES.0000173297.53793.fa
[13] Balsam, L.B., Wagers, A.J., Christensen, J.L., Kofidis, T., Weissman, I.L. and Robbins, R.C. (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 428, 668-673. doi:10.1038/nature02460
[14] Hatzistergos, K.E., Quevedo, H., Oskouei. B.N., Hu, Q., Feigenbaum, G.S., Margitich, I.S., Mazhari, R., Boyle, A.J., Zambrano, J.P., Rodriguez, J.E., Dulce, R., Pattany, P.M., Valdes, D., Revilla, C., Heldman, A.W., McNiece, I. and Hare, J.M. (2010) Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circulation Research, 107, 913-922. doi:10.1161/CIRCRESAHA.110.222703
[15] Porrello, E.R., Mahmoud, A.I., Simpson, E., Hill, J.A., Richardson, J.A., Olson, E.N. and Sadek, H.A. (2011) Transient regenerative potential of the neonatal mouse heart. Science, 331, 1078-1080. doi:10.1126/science.1200708
[16] Conlan, M.J., Rapley, J.W. and Cobb, C.M. (1996) Biostimulation of wound healing by low energy laser irradiation. Journal of Clinical Periodontology, 23, 492-496. doi:10.1111/j.1600-051X.1996.tb00580.x
[17] Karu, T. (2007) Ten lectures on basic science of laser photherapy. Prima Books, Gragesberg.
[18] Karu, T. (2010) Mitochondrial mechanisms of photobiomodulation in context of new data about multiple roles of ATP. Photomedicine and Laser Surgery, 28, 159-160. doi:10.1089/pho.2010.2789
[19] Bibikova, A. and Oron, U. (1993) Promotion of muscle regeneration in the toad (Bufo viridis) gastrocnemius muscle by low energy laser irradiation. Anatomical Record, 235, 374-380. doi:10.1002/ar.1092350306
[20] Bibikova, A., Belkin, A. and Oron, U. (1994) Enhancement of angiogenesis in regenerating gastrocnemius muscle of the toad (Bufo viridis) by low energy laser irradiation. Anatomy and Embryology, 190, 597-602. doi:10.1007/BF00190110
[21] Oron, U. (2006) Photoengineering of tissue repair in skeletal and cardiac muscles. Photomedicine and Laser Surgery, 24, 111-120. doi:10.1089/pho.2006.24.111
[22] Yaakobi, T., Shoshani, Y., Levkovitz, S., Rubin, O., Ben-Haim, S.A. and Oron, U. (2001) Long term effect of low energy laser irradiation on infarction and reperfusion injury in the rat heart. Journal of Applied Physiology, 90, 2411-2441.
[23] Oron, U., Yaakobi, T., Oron, A., Hayam, G., Gepstein, L., Wolf, T., Rubin, O. and Ben Haim, S.A. (2001a) Attenuation of the formation of scar tissue in rats and dogs post myocardial infarction by low energy laser irradiation. Lasers in Surgery and Medicine, 28, 204-211. doi:10.1002/lsm.1039
[24] Oron, U., Yaakobi, T., Oron, A., Mordechovitz, D., Shofti, R., Hayam, G., Dror, U., Gepstein, L., Wolf, T., Haudenschild, C. and Ben Haim, S.A. (2001b) Low energy laser irradiation reduces formation of scar tissue following myocardial infarction in dogs. Circulation, 103, 296-301. doi:10.1161/01.CIR.103.2.296
[25] Tuby, H., Maltz, L. and Oron, U. (2006) Modulations of VEGF and iNOS in the rat heart by low energy laser irradiation are associated with cardioprotection and enhanced angiogenesis. Lasers in Surgery and Medicine, 38, 682-688. doi:10.1002/lsm.20377
[26] Oron, U., Ilic, S., De Taboada, L. and Streeter, J. (2007) Ga-As (808 nm) laser irradiation enhance ATP production in human neuronal cells in culture. Photomedicine and Laser Surgery, 25, 180-182. doi:10.1089/pho.2007.2064
[27] Tuby, H., Maltz, L. and Oron, U. (2007) Low-level laser irradiation (LLLI) promotes proliferation of mesenchymal and cardiac stem cells in culture. Lasers in Surgery and Medicine, 39, 373-378. doi:10.1002/lsm.20492
[28] Li, W.T., Leu, Y.C. and Wu, J.L. (2010) Red-light lightemitting diode irradiation increases the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells. Photomedicine and Laser Surgery, 28, S-157-S-165. doi:10.1089/pho.2009.2540
[29] Mvula, B., Moore, T.J. and Abrahamse, H. (2010) Effect of low-level laser irradiation and epidermal growth factor on adult human adipose-derived stem cells. Lasers in Medical Science, 25, 33-39. doi:10.1007/s10103-008-0636-1
[30] Tuby, H., Maltz, L. and Oron, U. (2011) Induction of autologous mesenchymal stem cells in the bone marrow by low-level laser therapy has profound beneficial effects on the infarcted rat heart. Lasers in Surgery and Medicine, 43, 401-409. doi:10.1002/lsm.21063
[31] Oron, U. (2011) Light therapy and stem cells: A therapeutic intervention of the future. Journal of Interventional Cardiology, 3, 627-629.
[32] Toma, C., Pittenger, M.F., Cahill, K.S., Byrne, B.J. and Kessler, P.D. (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation, 105, 93-98. doi:10.1161/hc0102.101442
[33] Oron, U. and Mandelberg, M. (1985) Focal regeneration in the rat myocardium following cold injury. Cell Tissue Research, 241, 459-463. doi:10.1007/BF00217194
[34] Mummery, C.L., Davis, R.P. and Krieger, J.E. (2010) Challenges in using stem cells for cardiac repair. Science Translational Medicine, 14, 1-5.
[35] van Amerongen, M.J., Harmsen, M.C., van Rooijen, N., Petersen, A.H. and van Luyn, M.J. (2007) Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. American Journal of Pathology, 170, 1093-1103. doi:10.2353/ajpath.2007.060547
[36] Okazaki, T., Ebihara, S., Asada, M., Yamanda, S., Saijo, Y., Shiraishi, Y., Ebihara, T., Niu, K., Mei, H., Arai, H. and Yambe, T. (2007) Macrophage colony-stimulating factor improves cardiac function after ischemic injury by inducing vascular endothelial growth factor production and survival of cardiomyocytes. American Journal of Pathology, 171, 1093-1103. doi:10.2353/ajpath.2007.061191

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