The Effects of Adipose-Derived Stem Cell-Differentiated Adipocytes on Skin Burn Wound Healing in Rats.

Both adipose-derived stem cells (ADSCs) and fat grafting promote burn wound healing, but whether adipogen-derived cells using various inducers such as 3-isobutyl-1-methylxanthine (IBMX) and insulin affect wound healing is unknown. Herein, ADSC-differentiated adipogenic lineages were used in rat burn wounds to evaluate wound healing potential. ADSCs were cultivated using six different adipogenic differentiation conditions (IBMX ± insulin, IBMX for 5 days, high and low Dulbecco's modified Eagle's medium) and in vitro morphological changes and cell proliferations during adipogenic differentiation were recorded. Intermediate burn wounds were inflicted in 15 Wistar male rats. Afterwards, the rats were divided into five groups for subcutaneous injections under the wounds: control; ADSCs; differentiated adipocytes (-IBMX+INSULIN and +IBMX[D1-5]+INSULIN) and fat prepared by Coleman technique. Macroscopic changes and histology were documented for 3 weeks. Repeated measures analysis of variance was performed to analyze cell growth and wound healing with a statistical level set of P < .05. Induction cocktails significantly reduced proliferation and induced lipid droplet accumulation. Conditioning without insulin induced the least lipid accumulation, while discontinuing IBMX generated larger adipocytes (P < .001). Adipogenic differentiated ADSCs had similar wound healing abilities with ADSC and fat injections, but differentiated adipocytes (+IBMX[D1-5]+INSULIN) and fat grafting accelerated the early healing process relative to ADSC (P < .001). Reduced fibrosis and mild inflammatory infiltration limited to superficial dermis were observed in +IBMX(D1-5)+INSULIN and fat injection groups, while those reactions were mild to moderate in ADSC group. Differentiated adipocytes achieve similar wound healing results compared with ADSC and fat injections, but differentiated adipocytes (+IBMX[D1-5]+INSULIN) and fat grafting accelerate early healing relative to ADSC.