Systemic Administration of Adipose-Derived Stem Cells Immediately after Radiotherapy to Prevent Development of Late Radiation-Induced Damage.

Abstract

Radiotherapy is a well-established cancer treatment, but its detrimental effects on normal tissue have been underestimated. Late radiation-induced tissue damage leads to dysfunction, such as loss of elasticity and delayed wound healing, which negatively affect the prognosis and quality of life of cancer survivors. The authors' previous research demonstrated that local prophylactic administration of adipose-derived stem cells (ASCs) immediately after irradiation could prevent late radiation-related disorders. This study explored the effects of systemic administration of ASCs for future clinical applications. Nude mice were irradiated on their dorsal skin (40 Gy total: 2 Gy × 20, simulating clinical radiotherapy). Human ASCs were administered systemically (through intravenous or intraperitoneal injection, once or twice). Control groups included a nonirradiated group and a vehicle-treated radiotherapy group. After 6 months, full-thickness skin wounds were created on the mice's dorsal skin and observed for 28 days. The wound-healing process was assessed, and tissue samples were analyzed using immunohistochemistry. Radiotherapy caused subcutaneous fat atrophy and fibrosis at 6 months, which was effectively prevented in the ASC-treated groups. Wound healing was faster in the ASC-treated groups than in the vehicle-treated groups, although not as fast as in the no-radiotherapy group. ASC-treated groups exhibited less fat layer atrophy and fibrosis than vehicle-treated groups. Engraftment of ASCs was confirmed in the fatty layer of the irradiated skin. Prophylactic systemic administration of ASCs immediately after radiotherapy can prevent tissue damage and dysfunction associated with radiation therapy. A combination of radiotherapy and stem cell therapy can be the optimal treatment strategy to maximize the effects for cancer and minimize radiation damage in the future.