Implantation of low-level laser irradiated mesenchymal stem cells into the infarcted rat heart is associated with reduction in infarct size and enhanced angiogenesis

Hana Tuby, M.Sc., Lidya Maltz, M.Sc., and Uri Oron, Ph.D., Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, 69978, Israel

Abstract

Objective: The aim of the present study was to evaluate the possible beneficial effects of implantation of laser-irradiated mesenchymal stem cells (MSCs) into the infarcted rat heart. Background data: It was demonstrated that Low-level laser therapy (LLLT) upregulates cytoprotective factors in ischemic tissues. Materials and Methods: MSCs were isolated from rat bone marrow and grown in culture. The cells were laser irradiated with Ga-Al-As laser (810nm wavelength), labeled with 5-Bromo-2'deoxyuridine (BrdU), and then implanted into infarcted rat hearts. Non-irradiated cells were similarly labeled and acted as control. Hearts were excised three weeks later and cells were stained for BrdU and c-kit immunoreactivity. Results: Infarcted hearts that were implanted with laser-treated cells showed a significant reduction of 53% in infarct size compared to hearts that were implanted with non-laser-treated cells. The hearts implanted with laser-treated cells prior to implantation demonstrated a 5 and 6.3-fold significant increase in cell density that positively immunoreacted to BrdU and c-kit, respectively, as compared to hearts implanted with non-laser-treated cells. A significantly 1.4 and 2-fold higher level of angiogenesis and vascular endothelial growth factor, respectively, was observed in infarcted hearts that were implanted with laser-treated cells as compared to non-treated implanted cells. Conclusion: The findings of the present study provide the first evidence that LLLT can significantly increase survival and/or proliferation of MSCs post implantation into the ischemic/infarcted heart, followed by a marked reduction of scarring, and enhanced angiogenesis. The mechanisms associated with this phenomenon remain to be elucidated in further studies.