INTRODUCTION: Adipose derived Stem Cells (ASCs) have been proven to play a key role in tissue regeneration. However, exposure to large amounts of cigarette smoke can drastically diminish their function. Erythropoetin (EPO), can modulate cellular response to injury. Therefore, we investigated the ability of EPO to restore the regenerative function and differentiation capacity of ASCs. MATERIAL AND METHODS: Human ASCs were isolated from abdominoplasty samples using standard isolation procedures. Cell identity was established by means of Fluorescence Activated Cell Scanning. Subsequently, isolated ASCs were cultivated with cigarette smoke extract both with and without EPO. Parameters investigated included cellular metabolic activity, adipogenic and osteogenic differentiation capacity, and in vitro wound closure capacity. For further enhancing wound closure, EPO was combined with Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) or Stromal Derived Factor-1 alpha (SDF-1 a). RESULTS: Cigarette smoke reduces adipogenic differentiation, the osteogenic differentiation capacity as well as the in vitro wound healing ability of human derived ASCs. EPO did not change metabolic activity of ASCs significantly. The addition of EPO could partially restore their function. The combination of EPO with GM-CSF or SDF-1 did not result in a synergistic effect regarding wound healing ability. CONCLUSION: Exposure to cigarette smoke significantly reduced the regenerative potential of ASCs. Treatment of ASCs exposed to cigarette smoke with EPO has the potential to partially restore their function.