Carnitine and acetylcarnitine modulate mesenchymal differentiation of adult stem cells

Abstract

Cellular metabolic activity, especially mitochondrial metabolism, plays a vital role in regulating cell proliferation and differentiation. Metabolism could therefore be an important factor to consider when using engineering technologies to stimulate tissue development and repair. The small metabolite carnitine and its derivative acetylcarnitine affect the activities of several pathways in mitochondrial metabolism, but their influence on cell differentiation has not yet been thoroughly studied. To elucidate the effects of these two small molecules on mesenchymal tissue engineering, we used adult stem cells as a platform in both monolayer and 3D hydrogel culture systems. We investigated the impact of these two small molecules on the differentiation of adult stem cells and analysed gene expression, cell proliferation and extracellular matrix deposition. We found that the molecules reduced adipogenesis but stimulated osteogenesis and chondrogenesis in both culture systems. Our results suggest that carnitine and acetylcarnitine could affect the differentiation rate of adult stem cells by regulating mitochondrial metabolism. The effects of these two small molecules give rise to the possibility of employing such metabolites in tissue-engineering systems to enhance cell differentiation and tissue development.

Keywords: acetylcarnitine; adult stem cells; carnitine; mesenchymal differentiation; mitochondrial metabolism; tissue engineering.