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Investigation of Stem-like Cells Role in Regional Radiosensitivity of the Lung
Ola M Maria, Ahmed M Maria, Norma Ybarra, Krishinima Jeyaseelan, Sangkyu Lee, Jessica Perez, Shirley Lehnert, Lyne Kharbotly, Sergio Faria, Monica Serban, Jan Seuntjens and Issam El Naqa
Objective: Lung is a complex organ with puzzling patterns of radiosensitivity, depending on both the volume and the region of the lung irradiated. In this study, we aimed to investigate stem-like cells distribution in lung lobes and their potential role in regional radiosensitivity and incidences of radiation-induced lung damage (RILD).
Methods: Fifteen male Sprague-Dawley rats (8 weeks, 200–250 g) were grouped into two groups: control (sham irradiated, n=6) and treatment (irradiated, n=9). The treatment group received 3 regimens of whole thorax x-ray doses and divided into 3 subgroups: 12 Gy (n=3), 16 Gy (n=3) and 20 Gy (n=3), and monitored for 16 weeks post-radiation. Immunohistochemistry techniques were employed to localize and quantify the distribution of type II pneumocytes, Clara cells and cluster of differentiation (CD) positive stem cells (CD24+, CD44v6+, CD73+), in the upper, middle and lower lobes of the right lung in all rats.
Results: The upper lobe was found to harbour more stem-like cells compared to the middle/lower lobes (p < 0.05). The middle and lower lobes contained comparable percentages of different stem-like cells. All stem-like cells tested were distributed unsystematically in the lung tissue with no specific identifiable niches.
Conclusion: The upper lobe harbours more population of stem-like cells compared to the lower lobe, this might explain the variation in regional radiosensitivity, with the lower lung lobe being more prone to radiation injury compared to the upper lobe. No specific stem cell niche could be identified in our study. These results may support the development of new-targeted radioprotection strategies to reduce incidences of RILD during radiotherapy.