Abstract
BackgroundAdipose-derived stem cells (ASCs) are important to homeostasis and the regeneration of subcutaneous fat. Hence, we examined the proliferation and differentiation capacity of irradiated ASCs over time.MethodsTwo female pigs received a single 18 Gy dose of ionizing radiation to an 18 × 8 cm area on the dorsal body skin via a 6 MeV electron beam. After irradiation, the ASCs were cultured from adipose tissue harvested from a non-irradiated area and an irradiated area at 2, 4, and 6 weeks. The proliferation capacity of ASCs was evaluated by a colony-forming units–fibroblasts (CFUs-Fs) assay, a cholecystokinin (CCK) test with 10 % fetal bovine serum (FBS), and a 1 % FBS culture test. The senescence of ASCs was evaluated through morphological examination, immunophenotyping, and β-galactosidase activity, and the multipotent differentiation potential of ASCs was evaluated in adipogenic, osteogenic, and chondrogenic differentiation media.ResultsIrradiated ASCs demonstrated significantly decreased proliferative capacity 6 weeks after irradiation. As well, the cells underwent senescence, which was confirmed by blunted morphology, weak mesenchymal cell surface marker expression, and elevated β-galactosidase activity. Irradiated ASCs also exhibited significant losses in the capacity for adipocyte and chondrocyte differentiation. In contrast, osteogenic differentiation was preserved in irradiated ASCs.ConclusionsWe observed decreased proliferation and senescence of irradiated ASCs compared to non-irradiated ASCs 6 weeks after irradiation. Furthermore, irradiated ASCs demonstrated impaired adipocyte and chondrocyte differentiation but retained their osteogenic differentiation capacity. Our results could shed light on additional pathogenic effects of late irradiation, including subcutaneous fibrosis and calcinosis.
Highlights
Adipose-derived stem cells (ASCs) are important to homeostasis and the regeneration of subcutaneous fat
Subcutaneous fat is composed of various types of cells including adipocytes, mesenchymal stem cells termed as adipose tissue-derived stem cells (ASCs), vascular endothelial cells, and immune cells
The proliferation rate of ASCs was higher in the 6R group than the rates in the other groups when medium containing 1 % fetal bovine serum (FBS) was used as a cell stress test
Summary
Adipose-derived stem cells (ASCs) are important to homeostasis and the regeneration of subcutaneous fat. We examined the proliferation and differentiation capacity of irradiated ASCs over time. Radiotherapy is an effective treatment for cancer, ionizing radiation has side effects on the surrounding normal tissue, including skin and adipose tissue, and can cause injury to these tissues. Subcutaneous fat is composed of various types of cells including adipocytes, mesenchymal stem cells termed as adipose tissue-derived stem cells (ASCs), vascular endothelial cells, and immune cells. Mesenchymal stem cells including bone marrow-derived mesenchymal stem cells (BMSCs) and ASCs have various functions as progenitor cells and differentiate into adipocytes, osteoblasts, and chondrocytes [2, 3]. Patients that receive radiotherapy frequently experience atrophy of subcutaneous tissue
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