Small molecules modulate human adipose derived stem cell differentiation

Adipose‐derived stem cells (ASCs) are an abundant, readily available source of multipotent cells for regenerative medicine. Recently, stem cell metabolic oxidation state is indicated important for cell‐fate determination. Here we studied two amino acid like metabolites essential for mitochondria activity: L‐Carnitine (LC) and Acetyl‐L‐Carnitine (ALC), and their effects on human ASC differentiation. Specifically, we examined the proliferation and differentiation of human ASCs in adipogenic and osteogenic medium with LC (0 mM, 10 mM and 100 mM), or ALC (1 mM, 10 mM, and 100 mM). During adipogenic differentiation, both LC and ALC showed stronger depressing of lipid production as concentration increased, and ALC had stronger influence than LC, confirmed by Oil Red O staining and gene expression. During osteogenic differentiation, both LC and ALC improved osteogenesis, however with different optimal concentrations. In the LC group, a dose‐dependent increase in osteogenesis was observed, while in the ALC group, only 1 mM ALC showed positive influence, with stronger staining for Alizarin Red, significantly higher cell proliferation and mineral deposition. In conclusion, LC and ALC modulated human ASCs metabolic oxidation state, and influenced ASC differentiation. This work shows the potential of utilizing small molecules to stimulate target tissue production in regenerative medicine applications. Grant Funding Source : NIH