Embodiments of the disclosure include methods and compositions for use of prepared fibroblasts and/or conditioned media therefrom. In particular embodiments, the prepared fibroblasts have enhanced regenerative and may have an increase in secretion of one or more cytokines and/or growth factors; may have an increase in anti-apoptotic activity; and/or may have a modulated immunogenicity. In specific embodiments, the fibroblasts are prepared by exposure to hypoxia and/or carbon monoxide.