Comparing the cytotoxic effect of light-emitting and organic light-emitting diodes based light therapy on human adipose-derived stem cells

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Abstract

Light has attracted significant attention as a promising tool in the biomedical and cosmetic industries. However, little is known about the cytotoxic effects of conventional light sources based on their physical effects such as temperature and luminance. Here, the cytotoxic effects of representative light sources, a light-emitting diode (LED) and an organic light-emitting diode (OLED), were studied with human adipose-derived stem cells (hADSCs). Regardless of the identical light energy conditions, LED group induced a higher apoptotic activity in hADSCs than the OLED group due to its significant heat generation compared to OLED as further demonstrated with heat shock protein family gene expression. Additionally, we further confirmed the effect of luminance by irradiating light from LED and OLED under the same temperature and energy conditions. Increased cell proliferation was confirmed in the OLED group, and a significant expression of intracellular reactive oxygen species was observed in the LED group without showing heat shock protein upregulation. Taken together, the differences in cytotoxicity and cellular response after LED irradiation compared with OLED irradiation can be varied with temperature and luminance control. This study suggests that OLED based device could be an alternative and promising light source for future biomedical and cosmetic applications.

Introduction

Owing to their therapeutic properties, stem cells (SCs) have attracted enormous attention as a powerful tool in tissue regeneration [1], [2]. It is well-known that the SCs can differentiate into a variety of cells, and have self-renewal properties [3], [4]. In addition to their multipotent and self-renewal properties, SCs also secrete paracrine factors that can promote the recovery of impaired tissue. Paracrine factors secreted from injected SCs can stimulate tissue repair by recruiting supportive cells and inducing the differentiation of innate SCs at the impaired area [5], [6], [7]. However, the low survival rate of the injected cells has been considered as a main obstacle in SC therapy [8], [9]. Therefore, researchers have attempted to increase the therapeutic potential of SCs by introducing growth factors [10], genes [11], and scaffolds [12], [13]. However, these methods are accompanied by crucial drawbacks such as high cost, potential toxicity, and immune responses toward clinical applications [14], [15], [16]. Thus, researchers considered focusing on applying extrinsic stimulations, such as mechanical cues, electrical stimulation, and even light to SCs for enhancing the therapeutic efficiency [17], [18], [19].

Among the aforementioned stimulations, light is presently attracting enormous attention as an intriguing stimulation in SC therapy [20], [21], [22], [23], [24]. Although the mechanism of light stimulation has not been fully elucidated, reactive oxygen species (ROS) are considered as one of the major factors accounting for SC biomodulation. Although ROS can be considered as toxic factor resulting downregulation of extracellular signaling related kinases and upregulate apoptotic pathways, a mild level of ROS can induce redox signaling that can promote cell proliferation, differentiation, and even stem cell renewal [25], [26], [27], [28]. Several factors of light including wavelength, luminance, and energy density are known to affect ROS generation [29], [30], [31]. To control the ROS generation, most of research has chosen red light, because short wavelength light at the range of blue has been discovered to show harmful effect on cells due to its excessive ROS generation property [29], [30]. Controlling luminance and energy density are also key factors for the prevention of an excessive ROS generation [31].

In the perspective of light source, however, little is known about the effect of specific light source in light therapy. Previous studies mostly have chosen to use laser or light emitting diode (LED) for the biomedical application, but not organic light emitting diode (OLED) [20], [21], [23], [26], [31], [32], [33]. Point source of light system of LED makes it hard to deliver light energy evenly on the surface area. New developments of LED have been reported recently, which can decrease heat generation and increase light dissipative property of LED by inventing printed circuit board and manufacturing micro-LED. However, high cost and relatively low impact resistance are considered as a problem needed to be elucidated for bio-application. In stark contrast to LED, OLED has broad spectrum similar to natural light, showing relatively low luminance and energy density together [34], [35]. Moreover, OLEDs create light within the area that can deliver light evenly on the surface. Because of flexible property, OLED has been adopted as an alternative light source for flexible future device together with its light weight [36], [37], [38]. Ultrathin OLED, for example, showed impressive flexibility more suitable for curved structure of our body [39], [40]. Stability concerns regarding ultrathin OLED also have been developed in the recent study [41]. OLED also shows lower heat generation compared to LED due to its heat dissipative property, which may be more suitable for cell culture and attachment to the human body [36], [42]. Although heat can be crucial factor for light therapy in the perspective of ROS generation, still the effect of heat in light therapy remains uncovered.

The hADSCs have been widely used in tissue engineering based on their high therapeutic efficacy. hADSCs are known to have great potential in specific cell differentiation, therapeutic paracrine factor secretion, and easy sample collection toward clinical application. The advantages lead hADSCs more suitable for cell therapy compared to other cell types [43], [44]. In this study, we compared the phototoxic effects of LED and OLED devices on human adipose-derived SCs (hADSCs) by irradiating light possessing the same energy but different energy densities under heat or heat-excluded conditions. We further confirmed whether the same light energy from the LED or OLED device could induce phototoxicity and stimulate specific gene expressions in the irradiated group compared with in the non-irradiated one (Fig. 1a).

Section snippets

Device setting

We wrapped the OLED panel with transparent plastic bags to further protect the device from the 95% humidity environment while using it in the incubator. The power supply was installed on the incubator, and the OLED panel was connected to a power supply as an energy supplement (Fig. 5A). The OLED panel was operated at a voltage of 3.50. The LED panel was installed either inside or outside incubator depending on culture condition (Fig. 5A). Both LED and OLED panel were 8 cm in length and 8 cm in

Results

As shown in Fig. 1b, the changes in the temperatures of the light sources with the driving time were significantly different between the LED and OLED groups: the temperature of the LED group increased rapidly with time and was maintained at > 60 °C after 10 min of irradiation, while that of the OLED group was maintained at 27 °C for 30 min. After 5 min of irradiation, the temperatures of the light sources were randomly measured according to their locations (Fig. 1c). LED (the point light

Discussion

Among the numerous methods of increasing the therapeutic efficacy of SCs, light has been adopted as a promising, alternative tool which could avoid the potential side effects that are associated with the application of extrinsic biomaterials. Although there are several studies on LLLT regarding the wavelength and energy density of light, the effects of light sources on LLLT are vague. Although previous studies on LLLT mostly used LED as the light source, light from LEDs possess relatively high

Conclusion

We compared the effect of LED- and OLED-based LLLT on hADSCs to the cell culture system to identify the differences in the cellular behaviors. Since tissue is composed of complex structures, it was challenging to expose entire cells to light in vivo. Therefore, we investigated the effect of light on hADSCs at the single-cell level. Owing to the heat-generation property of LED, LED-based LLLT caused cellular damages, such as apoptosis, in a conventional cell culture device (incubator).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) and the Ministry of Science and ICT (MSIT) (2019R1C1C1007384, 2018M3A9E2023255, 2021R1A4A1032782). This research was also supported by the KIST program (202011B31) through NRF and funded by MSIT. This work was partially funded by a grant from the Basic Science Research Program through NRF of Korea and funded by the Ministry of Science, ICT, and Future Planning (Grant no. 2019R1A2C2002390).

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