Lasers in Medical Science

, Volume 32, Issue 7, pp 1637–1646 | Cite as

Effect of low-level laser-treated mesenchymal stem cells on myocardial infarction

  • Zaynab H. El Gammal
  • Amr M. Zaher
  • Nagwa El-BadriEmail author
Review Article


Cardiovascular disease is the leading cause of death worldwide. Although cardiac transplantation is considered the most effective therapy for end-stage cardiac diseases, it is limited by the availability of matching donors and the complications of the immune suppressive regimen used to prevent graft rejection. Application of stem cell therapy in experimental animal models was shown to reverse cardiac remodeling, attenuate cardiac fibrosis, improve heart functions, and stimulate angiogenesis. The efficacy of stem cell therapy can be amplified by low-level laser radiation. It is well established that the bio-stimulatory effect of low-level laser is influenced by the following parameters: wavelength, power density, duration, energy density, delivery time, and the type of irradiated target. In this review, we evaluate the available experimental data on treatment of myocardial infarction using low-level laser. Eligible papers were characterized as in vivo experimental studies that evaluated the use of low-level laser therapy on stem cells in order to attenuate myocardial infarction. The following descriptors were used separately and in combination: laser therapy, low-level laser, low-power laser, stem cell, and myocardial infarction. The assessed low-level laser parameters were wavelength (635–804 nm), power density (6–50 mW/cm2), duration (20–150 s), energy density (0.96–1 J/cm2), delivery time (20 min–3 weeks after myocardial infarction), and the type of irradiated target (bone marrow or in vitro-cultured bone marrow mesenchymal stem cells). The analysis focused on the cardioprotective effect of this form of therapy, the attenuation of scar tissue, and the enhancement of angiogenesis as primary targets. Other effects such as cell survival, cell differentiation, and homing are also included. Among the evaluated protocols using different parameters, the best outcome for treating myocardial infarction was achieved by treating the bone marrow by one dose of low-level laser with 804 nm wavelength and 1 J/cm2 energy density within 4 h of the infarction. This approach increased stem cell survival, proliferation, and homing. It has also decreased the infarct size and cell apoptosis, leading to enhanced heart functions. These effects were stable for 6 weeks. However, more studies are still required to assess the effects of low-level laser on the genetic makeup of the cell, the nuclei, and the mitochondria of mesenchymal stromal cells (MSCs).


Cardiovascular diseases Low-level laser Low-power laser Laser parameters Laser effects Stem cell 



This work was supported by Science and Technology Development Fund in Egypt, grant number 5300 (Center of Excellence for Stem Cells and Regenerative Medicine).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    WHO (2013) Cardiovascular diseases (CVDs). WHO media centre, http://www.whoint/mediacentre/factsheets/fs317/en/indexhtml
  2. 2.
    Mazhari R, Hare JM (2007) Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche. Nat Clin Pract Cardiovasc Med 4:S21–S26CrossRefPubMedGoogle Scholar
  3. 3.
    El Gammal Z, Rashed L, Aziz M, Elwahy AH, Youakim M et al (2016) Comparative study between the attenuation of cardiac fibrosis by mesenchymal stem cells versus colchicine. Acta Medica Int 3:137–145CrossRefGoogle Scholar
  4. 4.
    Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C et al (2006) Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367:113–121CrossRefPubMedGoogle Scholar
  5. 5.
    Penicka M, Horak J, Kobylka P, Pytlik R, Kozak T et al (2007) Intracoronary injection of autologous bone marrow-derived mononuclear cells in patients with large anterior acute myocardial infarction. J Am Coll Cardiol 49:2373–2374CrossRefPubMedGoogle Scholar
  6. 6.
    Bartunek J, Vanderheyden M, Vandekerckhove B, Mansour S, De Bruyne B et al (2005) Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction. Circulation 112:I-178–I-183Google Scholar
  7. 7.
    Wollert KC, Meyer GP, Lotz J, Lichtenberg SR, Lippolt P et al (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364:141–148CrossRefPubMedGoogle Scholar
  8. 8.
    Rosenzweig A (2006) Cardiac cell therapy—mixed results from mixed cells. N Engl J Med 355:1274–1277CrossRefPubMedGoogle Scholar
  9. 9.
    Bersenev A, Levine BL (2012) Convergence of gene and cell therapy. Regen Med 7:50–56CrossRefPubMedGoogle Scholar
  10. 10.
    Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S et al (2003) Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium. Circulation 108:863–868CrossRefPubMedGoogle Scholar
  11. 11.
    Barboza CAG, Ginani F, Soares DM, Henriques ÁCG, Freitas RDA (2014) Low-level laser irradiation induces in vitro proliferation of mesenchymal stem cells. Einstein 12:75–81CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Tafur J, Mills PJ (2008) Low-intensity light therapy: exploring the role of redox mechanisms. Photomed Laser Surg 26:323–328CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Huang Y-Y, Chen AC-H, Carroll JD, Hamblin MR (2009) Biphasic dose response in low level light therapy. Dose Response 7:09–027CrossRefGoogle Scholar
  14. 14.
    Mvula B, Tj M, Abrahamse H (2010) Effect of low-level laser irradiation and epidermal growth factor on adult human adipose-derived stem cells. Laser Med Sci 25:33CrossRefGoogle Scholar
  15. 15.
    Park I-S, Chung P-S, Ahn JC (2014) Enhanced angiogenic effect of adipose-derived stromal cell spheroid with low-level light therapy in hind limb ischemia mice. Biomaterials 35:9280–9289CrossRefPubMedGoogle Scholar
  16. 16.
    Wu J-Y, Chen C-H, Wang C-Z, Ho M-L, Yeh M-L et al (2013) Low-power laser irradiation suppresses inflammatory response of human adipose-derived stem cells by modulating intracellular cyclic AMP level and NF-κB activity. PLoS One 8:e54067CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Villiers JAD, Houreld NN, Abrahamse H (2011) Influence of low intensity laser irradiation on isolated human adipose derived stem cells over 72 hours and their differentiation potential into smooth muscle cells using retinoic acid. Stem Cell Rev Rep 7:869–882CrossRefGoogle Scholar
  18. 18.
    Wu J-Y, Wang Y-H, Wang G-J, Ho M-L, Wang C-Z et al (2012) Low-power GaAlAs laser irradiation promotes the proliferation and osteogenic differentiation of stem cells via IGF1 and BMP2. PLoS One 7:e44027CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Tuby H, Maltz L, Oron U (2007) Low-level laser irradiation (LLLI) promotes proliferation of mesenchymal and cardiac stem cells in culture. Lasers Surg Med 39:373–378CrossRefPubMedGoogle Scholar
  20. 20.
    Hou J-F, Zhang H, Yuan X, Li J, Wei Y-J et al (2008) In vitro effects of low-level laser irradiation for bone marrow mesenchymal stem cells: proliferation, growth factors secretion and myogenic differentiation. Lasers Surg Med 40:726–733CrossRefPubMedGoogle Scholar
  21. 21.
    Soleimani M, Abbasnia E, Fathi M, Sahraei H, Fathi Y et al (2012) The effects of low-level laser irradiation on differentiation and proliferation of human bone marrow mesenchymal stem cells into neurons and osteoblasts—an in vitro study. Laser Med Sci 27:423–430CrossRefGoogle Scholar
  22. 22.
    Tuby H, Yaakobi T, Maltz L, Delarea Y, Sagi-Assif O et al (2013) Effect of autologous mesenchymal stem cells induced by low level laser therapy on cardiogenesis in the infarcted area following myocardial infarction in rats. J Biomed Sci Eng 6:24–31CrossRefGoogle Scholar
  23. 23.
    H Tuby, L Maltz, U Oron (2008) Low energy laser irradiation of stem cells for cardiac repair after myocardial infarction. International Conference of the World Association of Laser Therapy October 19–22:91–96Google Scholar
  24. 24.
    Tuby H, Maltz L, Oron U (2009) Implantation of low-level laser irradiated mesenchymal stem cells into the infarcted rat heart is associated with reduction in infarct size and enhanced angiogenesis. Photomed Laser Surg 27:227–233CrossRefPubMedGoogle Scholar
  25. 25.
    Moore P, Ridgway TD, Higbee RG, Howard EW, Lucroy MD (2005) Effect of wavelength on low-intensity laser irradiation-stimulated cell proliferation in vitro. Lasers Surg Med 36:8–12CrossRefPubMedGoogle Scholar
  26. 26.
    Jeffrey S Dover, Kenneth A Arndt (1990) Illustrated cutaneous laser surgery: a practitioner’s guide. Appleton & Lange,Google Scholar
  27. 27.
    Michael R Hamblin, Tatiana N Demidova (2006) Mechanisms of low level light therapy. Proc SPIE:614001–614012Google Scholar
  28. 28.
    Karu T (1998) Primary and secondary mechanisms of the action of monochromatic visible and near infrared radiation on cells. The science of low-power laser therapy. Gordon and Breach Science, AmsterdamGoogle Scholar
  29. 29.
    Laura Marinela Ailioaie, Da Chiran, Cc Ailioaie (2005) Biophysical and physiological mechanisms of low-energy lasers interactions with living cells and their implications in pain treatment. ANALELE ŞTIINŢIFICE ALE UNIVERSITĂŢII “AL I CUZA” IAŞI, Tomul I, s Biofizică, Fizică medicală şi Fizica mediuluiGoogle Scholar
  30. 30.
    Karu T, Eva NA’ (1995) Cytochrome c oxidase as a primary photoacceptor when laser irradiating cell culture by visible and near IR-range light. Dokl Akad Nauk 342:693–695PubMedGoogle Scholar
  31. 31.
    Ra C, Malatesta F, Darley-Usmar V (1983) Structure of cytochrome c oxidase. Biochim Biophys Acta 726:135–148CrossRefGoogle Scholar
  32. 32.
    Karu TI, Pyatibrat LV, Afanasyeva NI (2005) Cellular effects of low power laser therapy can be mediated by nitric oxide. Lasers Surg Med 36:307–314CrossRefPubMedGoogle Scholar
  33. 33.
    Walsh LJ, Trinchieri G, Waldorf HA, Whitaker D, Murphy GF (1991) Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci 88:4220–4224CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Zhang H, Hou J-F, Shen Y, Wang W, Wei Y-J et al (2010) Low level laser irradiation precondition to create friendly milieu of infarcted myocardium and enhance early survival of transplanted bone marrow cells. J Cell Mol Med 14:1975–1987CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Tuby H, Maltz L, 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 Surg Med 43:401–409CrossRefPubMedGoogle Scholar
  36. 36.
    Marques MM, Pereira AN, Fujihara NA, Nogueira FN, Eduardo CP (2004) Effect of low-power laser irradiation on protein synthesis and ultrastructure of human gingival fibroblasts. Lasers Surg Med 34:260–265CrossRefPubMedGoogle Scholar
  37. 37.
    Boulnois J-L (1986) Photophysical processes in recent medical laser developments: a review. Laser Med Sci 1:47–66CrossRefGoogle Scholar
  38. 38.
    Oron U, Yaakobi T, Oron A, Hayam G, Gepstein L et al (2001) Attenuation of infarct size in rats and dogs after myocardial infarction by low-energy laser irradiation. Lasers Surg Med 28:204–211CrossRefPubMedGoogle Scholar
  39. 39.
    Sommer AP, Pinheiro AL, Mester AR, Franke R-P, Whelan HT (2001) Biostimulatory windows in low-intensity laser activation: lasers, scanners, and NASA’s light-emitting diode array system. J Clin Laser Med Surg 19:29–33CrossRefPubMedGoogle Scholar
  40. 40.
    Calabrese EJ (2001) The future of hormesis: where do we go from here? Crit Rev Toxicol 31:637–648CrossRefPubMedGoogle Scholar
  41. 41.
    Bouvet-Gerbettaz S, Merigo E, Rocca J-P, Carle GF, Rochet N (2009) Effects of low-level laser therapy on proliferation and differentiation of murine bone marrow cells into osteoblasts and osteoclasts. Lasers Surg Med 41:291–297CrossRefPubMedGoogle Scholar
  42. 42.
    Smith KC (1990) Light and life: the photobiological basis of the therapeutic use of radiation from lasers. International Laser Therapy Association Conference, OsakaGoogle Scholar
  43. 43.
    Zhang Y, Zhang Z, Gao F, Hf T, Tergaonkar V et al (2015) Paracrine regulation in mesenchymal stem cells: the role of Rap1. Cell Death Dis 6:e1932CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Oron U, Yaakobi T, Oron A, Mordechovitz D, Shofti R et al (2001) Low-energy laser irradiation reduces formation of scar tissue after myocardial infarction in rats and dogs. Circulation 103:296–301CrossRefPubMedGoogle Scholar
  45. 45.
    Karu T (2001) Low-power laser effects. In: Lasers in medicine. CRC Press, Boca Raton, pp 171–209CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd. 2017

Authors and Affiliations

  • Zaynab H. El Gammal
    • 1
  • Amr M. Zaher
    • 2
  • Nagwa El-Badri
    • 1
    Email author
  1. 1.Center of Excellence for Stem Cells and Regenerative Medicine (CESC)Zewail City of Science and TechnologyCairoEgypt
  2. 2.National Institute of HeartCairoEgypt

Personalised recommendations