Light enhanced bone regeneration in an athymic nude mouse implanted with mesenchymal stem cells embedded in PLGA microspheres.

Ji Sun Park,Keun-Hong Park

doi:10.1186/s40824-016-0051-9

Abstract

BackgroundBiodegradable microspheres fabricated from poly (Lactic-co-glycolic acid) (PLGA) have attracted considerable attention in the bone tissue regeneration field. In this study, rabbit mesenchymal stem cells (rMSCs) adherent to PLGA microspheres were implanted into athymic nude mice and irradiated with 647 nm red light to promote bone formation. It was found that irradiating rMSCs with high levels of red light (647 nm) from an LED (light-emitting diode) increased levels of bone specific markers in rMSCs embedded on PLGA microspheres.ResultThese increased expressions were observed by RT-PCR, real time-QPCR, immunohistochemistry (IHC), and von Kossa and Alizarin red S staining. Microsphere matrices coated with rMSCs were injected into athymic nude mice and irradiated with red light for 60 seconds showed significantly greater bone-specific phenotypes after 4 weeks in vivo.ConclusionThe devised PLGA microsphere matrix containing rMSCs and irradiation with red light at 647 nm process shows promise as a means of coating implantable biomedical devices to improve their biocompatibilities and in vivo performances.

Highlights

Biodegradable microspheres fabricated from poly (Lactic-co-glycolic acid) (PLGA) have attracted considerable attention in the bone tissue regeneration field
We examined the effect of light from a red lightemitting diode on osteogenic differentiation of mouse mesenchymal stem cells (D1 cells) which were cultured in the presence of osteogenic differentiation medium (ODM) for 3 days, exposed to a red light-emitting diode (LED) light of 647 nm wavelength once for 10 s, 30 s and 90 s with radiation energies of 0.093 J, 0.279 J and 0.836 J, respectively [24]
To determine the effect of LED light on osteogenic differentiation, we transplanted rabbit mesenchymal stem cells (rMSCs) mixed with PLGA microspheres because the PLGA microspheres support cell proliferation

Summary

Introduction

Biodegradable microspheres fabricated from poly (Lactic-co-glycolic acid) (PLGA) have attracted considerable attention in the bone tissue regeneration field. Rabbit mesenchymal stem cells (rMSCs) adherent to PLGA microspheres were implanted into athymic nude mice and irradiated with 647 nm red light to promote bone formation. Many researchers in the tissue engineering field have focused on the roles of stem cells [4,5,6,7]. In terms of the application of LT, the wavelength of the light used is thought to stimulate or inhibit actions in cell and tissues. In clinical trials and in vivo, some ranges of wavelength, in particular, red to near IR, were thought be a useful for wound healing [15], peripheral and central nerve regeneration [16], and for the treatment of stomach and duodenal ulcers [17], because such light better penetrates tissues. The several types of cells were found to increase after exposure to low doses of laser irradiation, whereas cell growth and differentiation inhibitory effects were reported at higher doses due to accelerated ATP synthesis in cells [18,19,20,21,22,23] (Scheme 1)

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