Study of the effects of stromal vascular fraction, cultured adipose-derived stem cells, and paracrine factors of a conditioned medium in the treatment of severe radiation injuries of rat skin

Abstract

Aim. To study effects of stromal-vascular fraction (SVF) transplantation, cultured multipotent mesenchymal stem cells (MMSC) of adipose tissue, and administration of paracrine factors of the conditioned MMSC culture medium on the course of severe, local radiation lesions of the skin. Methods. Wistar-Kyoto rats were irradiated with X-rays at a dose of 110 Gy and a dose rate of 20.0 Gy/min. The tube voltage was 30 kV, current – 6.1 mA, filter –0.1 mm thick A1, and irradiation field area – 8.5 cm². Transplantation of adipose tissue SVF cells was performed twice at doses of 2.2 x 10⁶ and 3.0 x 10⁶ on the 28th and 35th days after irradiation, respectively. Cultured MMSC was administered at doses of 2.8 x 10⁶ and 3,4 x 10⁶ on the 28th and 35th days after irradiation. Paracrine factors of the conditioned medium were administered five times from the 1st to the 10th day after irradiation at a dose of 1.0 ml, s.c. (total protein, 8 mg/ml). Severity of radiation damage of the skin and effects of the therapy were followed up by clinical manifestations using planar geometry and pathomorphological methods. Results. Radiation exposure under the specified conditions caused severe radiation injuries of the skin with nonhealing ulcers that persisted for up to 5 months after irradiation. In control rats the area of radiation ulcers slowly decreased between the 28th and 84th days from 2.73 ± 0.17 cm² to 1.52 ± 0.17 cm², respectively, and was 0.52 ± 0.15 cm² and 0.05 ± 0.04 cm² at 4 and 5 months after irradiation. In all experimental groups, the healing was more intensive after the 84th day with a tendency to decrease the area of radiation ulcers; at 4 months after irradiation, statistically significant decreases in the area of ulcers and severity of lesions were observed in the experimental groups compared to the control (p <0.05). At four months after irradiation, 70-80% of rats in the treatment groups showed complete epithelialization of radiation wounds with formation of an atrophic scar whereas in the control group during the same period, atrophic scars were observed only in 40% of rats. Conclusion. Transplantation of adipose-derived SVF or cultured adipose tissue MMSC as well as administration of paracrine factors of the conditioned medium contributed to the enhancement of regenerative processes in the affected tissue and can be equally effective in the treatment of severe experimental radiation lesions of the skin.