title: 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.
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Qiaozhi
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Cellular and Molecular Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Yuanfan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D020219:Chondrogenesis / Q000187:drug effects*; D006041:Goats; D006801:Humans; D008648:Mesoderm; D010012:Osteogenesis / Q000187:drug effects*
chemical_list: D000108:Acetylcarnitine
keywords: acetylcarnitine; adult stem cells; carnitine; mesenchymal differentiation; mitochondrial metabolism; tissue engineering