Mesenchymal stem cells isolated from bone marrow and periodontal ligament respond to ionizing radiation by induction of stress-induced premature senescence without apparent differences in their radiation response.
Adult human dental pulp contains stem cells (DPSCs) that are capable of differentiation into osteoblasts, odontoblasts, adipocytes, and neuronal-like cells. Because these cells have potential use in tissue regeneration, herein we characterized the response of DPSC lines to ionizing radiation (IR). These DPSC lines have been developed from the extracted molars of healthy donors. DPSCs were cultivated in a unique media supplemented with epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). Since tissue homeostasis depends on a precise balance among cell proliferation, senescence, and cell death, we explored the effects of IR (2-20 Gy) on the proliferative activity of DPSCs and the molecular pathways involved. Even the highest dose used (20 Gy) did not induce DPSC apoptosis. After irradiation with doses of 6 and 20 Gy, DPSCs accumulated in the G2 phase of the cell cycle. DPSCs responded to IR (20 Gy) with senescence detected as SA-β-galactosidase positivity, beginning on the third day after irradiation. Twenty-four hours after irradiation, p53 and its serine 15 and 392 phosphorylated forms were detected. At this time, p21 (WAF1) was induced. Increases in protein p16 were observed from the third day following irradiation and continued till the end of the examination (Day 13). We conclude that DPSCs respond to IR-induced damage by permanent cell cycle arrest in the G2 phase and by stress-induced premature senescence.
Impaired diabetic wound healing is an important current medical issue, mainly concerning patients recovering from complicated operations or patients with ulcers on their feet. The obese Zucker diabetic fatty rat, with a mutation in leptin receptors, may be a good choice for studying impaired wound healing. Male and female rats were fed a diabetogenic high-fat diet. Wound size changes of air-exposed excisional 2 cm circular wounds were measured until Day 10. Wound tissue was analyzed morphologically, histologically, and immunohistochemically. The hydroxyproline content in the granulation tissue (GT) was determined. mRNA expression was assayed by DNA-array analysis and real-time reverse transcription-polymerase chain reaction. Wound-size changes were retarded in diabetic rats and differed between the sexes. Diabetic wounds were characterized by impaired contraction, abundant crust production, increased inflammation, and pus formation. On Day 10, the GT contained a significantly increased amount of intercalated fat tissue and showed an irregular arrangement of GT and collagen fibers. Interestingly, the length of new epithelium was increased in diabetic wounds. The concentration of hydroxyproline in the GT of diabetic animals was significantly decreased to about one half when compared with the nondiabetic controls. The expression of interleukin-6, myeloperoxidase, stromelysin-1, and collagenase-3 was increased in the GT of diabetic rats on Day 10, while the expression of type I collagen and elastin was decreased. Taken together, Zucker diabetic fatty rats exhibited impairments in wound-size reduction, inflammatory response, tissue organization, and connective tissue turnover and are thus proposed as a new model for studying impaired repair.
Dental pulp stem cells had a greater genotoxic stress response to cisplatin compared to HDFs. Cisplatin in higher concentrations triggered activation of MAPK and apoptosis in DPSCs but not in HDFs.
Hyiodine supports wound healing by stimulating wound contraction and epidermal proliferation and by keeping the wound moist through increased exudation.
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