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Emphysema is characterized by alveolar destruction and usually caused by chronic cigarette smoke exposure. Once the lesions are constituted no spontaneous regeneration process occurs. Rosiglitazone, an agonist of the peroxisome proliferator-activated receptor g (PPARg) pathway, and T0901317, an agonist of the sterol regulatory element binding protein (SREBP) pathway, could restore cell stem niche properties through differentiation of fibroblasts into lipofibroblasts (LIF). The aim of our work was first to evaluate the number of LIF in lungs of patients with or without emphysema. Secondly, we aimed to evaluate if the activation of the PPARg pathway or SREBP pathway with Rosiglitazone and T0901317 respectively could induce alveolar regeneration in vitro and in vivo in a murine model of emphysema.