Serum albumin maintains Wnt water-solubility and activity

Abstract Wnt proteins regulate adult tissue homeostasis and repair by driving stem cell self-renewal and differentiation. High-performance Wnt preparations have enormous therapeutic potential, especially alongside various stem cell technologies. Currently, most of these Wnt preparations contain Fetal Bovine Serum or the detergent CHAPS to maintain Wnt solubility and activity. Recently, afamin was identified as a serum factor that solubilizes Wnt3a in conditioned media, obviating the requirement for animal sera. Here, we report serum albumin is required for afamin-mediated solubilization of Wnt3a in conditioned media. Moreover, Serum Albumin-mediated solubilization of purified Wnt3a in tubes does not require afamin. This means conventional CHAPS-Wnt3a preparations can be modified into Serum Albumin-purified Wnt3a preparations by exchanging CHAPS for Serum Albumin through dialysis. Serum Albumin-purified Wnt3a preparations effectively promote the growth of human stem cell organoids. These data suggest Serum Albumin as a physiological factor for maintaining Wnt3a activity in therapeutic applications.