Therapeutic Effects of Human Adipose-Derived Products on Impaired Wound Healing in Irradiated Tissue

BACKGROUND:Clinical sequelae of irradiation (ischemia, fibrosis, and atrophy) result in tissue devitalization, where wound healing capacity is impaired. Fat or fat-derived products may work to treat such pathology. METHODS:Non-lethal irradiation at various doses (5 Gy, 10 Gy, 15 Gy) and frequencies (1-3 times on sequential days) was delivered to dorsal skin of 7-week-old nude mice, evaluating subsequent gross and microscopic changes for up to 4 weeks. Cutaneous punch wounds were then created, to compare wound healing in irradiated and non-irradiated states. Wounds were also locally injected with vehicle, cultured adipose-derived stem cells (ASCs), centrifuged fat tissue, or micronized cellular adipose matrix, monitoring therapeutic impact for up to 15 days. RESULTS:Nude mice given total doses >15 Gy spontaneously developed skin ulcers ~2 weeks after exposure and radiation damage was dose-dependent, but a fractionated irradiation protocol could reduce the damage. Histologic assessment revealed dose-dependent dermal fibrosis/thickening and subcutaneous atrophy. Dose-dependent (5-15 Gy) impairment of wound healing was also evident. At highest dosage (15 Gy × 3), open wounds persisted on Day 15. However, wounds injected with cultured ASCs were nearly healed on Day 12, and those treated with injection of centrifuged fat or micronized connective tissue healed faster than untreated controls (p