Induction of Autologous Bone-Marrow Stem Cells by Low-Level Laser Therapy Has Beneficial Effects on the Kidneys Post-Ischemia-Reperfusion Injury in the Rat

Hana Tuby, Lidya Maltz, Uri Oron

Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.

DOI: 10.4236/jbise.2014.78048                

Abstract

Acute renal failure has a 50% - 80% mortality rate. Currently, treatment options for this life-threatening disease are limited. Low-level laser therapy (LLLT) has been found to modulate biological activity. The aim of the present study was to investigate the possible beneficial effects of laser application to stem cells in the bone marrow, on the kidneys of rats that had undergone ischemia-reperfusion injury (IRI). IRI was induced by occlusion of the renal artery to 3- and 7-month-old rats for 15 or 30 minutes. In an additional experiment IRI was applied to both kidneys for 20 min each in 2-3-month-old rats. Rats were then divided randomly into two groups of control and laser-treated. Laser therapy (Ga-Al-As 810 nm, 200 mW output for 2 min) was applied to the bone marrow 1 and 7 days post-IRI to the kidneys, and rats were sacrificed 2 weeks later. Histomorphometry and immunohistochemistry were performed on kidney sections and blood markers for kidney function. Quantitative histomorphometric analysis revealed a reduction in dilatation of the renal tubules, restored structural integrity of the renal tubules, and reduced necrosis in the laser-treated rats as compared to the control, non-laser-irradiated group. C-kit positive cell density in kidneys post-IRI and laser-treatment was significantly (p = 0.015) 3.2-fold higher compared to the control group. Creatinine and blood urea nitrogen content were significantly lower in the laser-treated rats as compared to control. It is concluded that LLLT application to the bone marrow (BM) causes a significant increase in the density of mesenchymal stem cells in the kidneys post-IRI, probably by induction of stem cells in the BM, which subsequently migrate to the IRI kidney, significantly reducing the pathological features of the kidney and increasing kidney function post IRI.

Keywords

Kidney, Mesenchymal Stem Cells (MSCs), Low-Level Laser Therapy (LLLT), Ischemia-Reperfusion Injury (IRI)

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Morigi, M., Benigni, A., Remuzzi, G. and Imberti, B. (2006) The Regenerative Potential of Stem Cells in Acute Renal Failure. Cell Transplant, 15, S111-S117. http://dx.doi.org/10.3727/000000006783982449
[2]	Lin, F., Cordes, K., Li, L., Hood, L., Couser, W.G., Shankland, S.J. and Igarashi, P. (2003) Hematopoietic Stem Cells Contribute to the Regeneration of Renal Tubules after Renal Ischemia-Reperfusion Injury in Mice. Journal of the American Society of Nephrology, 14, 1188-1199. http://dx.doi.org/10.1097/01.ASN.0000061595.28546.A0
[3]	Stokman, G., Leemans, J.C., Cleassen, N., Weening, J.J. and Florquin, S. (2005) Hematopoeitic Stem Cell Mobilization Therapy Accelerates Recovery of Renal Function Independent of Stem Cell Contribution. Journal of the American Society of Nephrology, 16, 1684-1692. http://dx.doi.org/10.1681/ASN.2004080678
[4]	Cantley, L.G. (2005) Adult Stem Cells in the Repair of the Injured Renal Tubule. Nature Clininical Practice Nephrology, 1, 22-32. http://dx.doi.org/10.1038/ncpneph0021
[5]	Wang, Y., Hu, F., Wang, Z.J., Wang, G.X., Zhang, Z.H., Xie, P. and Cui. S.P. (2008) Administration of Bone Marrow-Derived Stem Cells Suppresses Cellular Necrosis and Apoptosis Induced by Reperfusion of Ischaemic Kidneys in Rats. Chinese Medical Journal, 121, 268-271.
[6]	Stockman, G., Stroo, I., Claessen, N., Teske, G.J.D., Leemans, J.C. and Florquin, S. (2010) Stem Cell Factor Expression after Renal Ischemia Promotes Tubular Epithelial Survival. PLoS One, 21;5(12):e14386.
[7]	Zarjou, A., Sanders, P.W., Mehta, R.L. and Agarwal, A. (2012) Enabling Innovative Translation Research in Acute Kidney Injury. Clinical and Translational Science, 5, 93-101. http://dx.doi.org/10.1111/j.1752-8062.2011.00302.x
[8]	Togwl, F.E., and Westen-felder, C. (2012) Kidney Protection and Regeneration Following Acute Injury: Progress Through Stem Cell Therapy. American Journal of Kidney Diseases, 60, 1012-1022. http://dx.doi.org/10.1053/j.ajkd.2012.08.034
[9]	Fangming, L. (2006) Stem Cells in Kidney Regeneration Following Acute Renal Injury. Pediatric Research, 59, 74R-78R. http://dx.doi.org/10.1203/01.pdr.0000205156.85990.12
[10]	Lange, C., Tögel, F., Ittrich, H., Clayton, F., Nolte-Ernsting, C., Zander, A.R. and Westenfelder, C. (2005) Administered Mesenchymal Stem Cells Enhance Recovery from Ischemia/Reperfusion-Induced Acute Renal Failure in Rats. Kidney International, 68, 1613-1617. http://dx.doi.org/10.1111/j.1523-1755.2005.00573.x
[11]	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. http://dx.doi.org/10.1111/j.1600-051X.1996.tb00580.x
[12]	Karu, T. (2007) Ten Lectures on Basic Science of Laser Phototherapy. Gragesberg Sweden. Prima Books.
[13]	Karu, T. (2010) Mitochondrial Mechanisms of Photo-biomodulation in Context of New Data about Multiple Roles of ATP. Photomedicine and Laser Surgery, 28, 159-160. http://dx.doi.org/10.1089/pho.2010.2789
[14]	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. http://dx.doi.org/10.1002/ar.1092350306
[15]	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. http://dx.doi.org/10.1007/BF00190110
[16]	Oron, U. (2006) Photoengineering of Tissue Repair in Skeletal and Cardiac Muscles. Photomedicine and Laser Surgery, 24, 111-120. http://dx.doi.org/10.1089/pho.2006.24.111
[17]	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, 2411-2419.
[18]	Oron, U., Yaakobi, T., Oron, A., Mordechovitz, D., Shofti, R., Hayam, G., Dror, U., Gepstein, L., Wolf, T., Haudenschild, C. and Ben-Haim, SA. (2001) Low Energy Laser Irradiation Reduces Formation of Scar Tissue Following Myocardial Infarction in Dogs. Circulation, 103, 296-301. http://dx.doi.org/10.1161/01.CIR.103.2.296
[19]	Oron, U., Yaakobi, T., Oron, A., Hayam, G., Gepstein, L., Wolf, T., Rubin, O. and Ben-Haim, S.A. (2001) Attenuation of Infarct Size in Rats and Dogs after Myocardial Infarction by Low-Energy Laser Irradiation. Lasers in Surgery and Medicine, 28, 204-211. http://dx.doi.org/10.1002/lsm.1039
[20]	Tuby, H., Maltz, L. and Oron, U. (2006) Modulations of VEGF and iNOS in the Rat Heart by Low Level Laser Therapy are Associated with Cardioprotection and Enhanced Angiogenesis. Lasers in Surgery and Medicine, 38, 682-688. http://dx.doi.org/10.1002/lsm.20377
[21]	Oliveira, F.A., Moraes, A.C., Paiva, A.P., Schinzel, V., Correa-Costa, M., Semedo, P., Castoldi, A., Cenedeze, M.A., Oliveira, R.S., Bastos, M.G., Camara, N.O. and Sanders-Pinheiro, H. (2012) Low-Level Laser Therapy Decreases Renal Interstitial Fibrosis. Photomedicine and Laser Surgery, 30, 705-713. http://dx.doi.org/10.1089/pho.2012.3272
[22]	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. http://dx.doi.org/10.1089/pho.2007.2064
[23]	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. http://dx.doi.org/10.1002/lsm.20492
[24]	Li, W.T., Leu, Y.C. and Wu, J.L. (2010) Red-Light Light-Emitting Diode Irradiation Increases the Proliferation and Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells. Photomedicine and Laser Surgery, 28, S157-S165. http://dx.doi.org/10.1089/pho.2009.2540
[25]	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. http://dx.doi.org/10.1007/s10103-008-0636-1
[26]	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. http://dx.doi.org/10.1002/lsm.21063
[27]	Oron, U. (2011) Light Therapy and Stem Cells: A Therapeutic Intervention of the Future. Interventional Cardiology, 3, 627-629. http://dx.doi.org/10.2217/ica.11.74
[28]	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. http://dx.doi.org/10.4236/jbise.2013.68A1003
[29]	Mummery, C.L., Davis, R.P. and Krieger, J.E. (2010) Challenges in Using Stem Cells for Cardiac Repair. Science Translational Medicine, 2, 27.
[30]	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. http://dx.doi.org/10.1161/CIRCRESAHA.110.222703
[31]	Cristy, M. (1981) Active Bone Marrow Distribution as a Function of Age in Humans. Physics in Medicine and Biology, 26, 389-400. http://dx.doi.org/10.1088/0031-9155/26/3/003
[32]	Ilic, S., Leichliter, S., Streeter, J., Oron, A., DeTaboada, L. and Oron, U. (2006) Effects of Power Densities, Continuous and Pulse Frequencies and Number of Sessions of Low Level Laser Therapy on Intact Rat Brain. Photomedicine and Laser Surgery, 24, 458-466. http://dx.doi.org/10.1089/pho.2006.24.458
[33]	Zivin, J.A., Albers, G.W., Bornstein, N., Chippendale, T., Dahlof, B., Devlin, T., Fisher, M., Hacke, W., Holt, W., Ilic, S., Kasner, S., Lew, R., Nash, M., Peres, J., Rymer, M., Schellinger, P., Scheunder, D., Schwab, S., Veltkamp, R., Walker, M. and Streeter, J. (2009) Effectiveness and Safety of Transcranial Laser Therapy for Acute Ischemic Stroke. Stroke, 40, 1359-1364.
[34]	Tuby, H., Hertzberg, E., Maltz, L. and Oron, U. (2013) Long-Term Safety of Low-Level Laser Therapy at Different Power Densities and Single or Multiple Applications to the Bone Marrow in Mice. Photomedicine and Laser Surgery, 31, 269-273.