Abstract
BackgroundThe study of lipid metabolism in stem cell physiology has recently raised great interest. The role of lipids goes beyond the mere structural involvement in assembling extra- and intra-cellular compartments. Nevertheless, we are still far from understanding the impact of membrane lipidomics in stemness maintenance and differentiation patterns. In the last years, it has been reported how in vitro cell culturing can modify membrane lipidomics. The aim of the present work was to study the membrane fatty acid profile of mesenchymal stromal cells (MSCs) derived from human fetal membranes (hFM-MSCs) and to correlate this to specific biological properties by using chemically defined tailored lipid supplements (Refeed®).MethodsFreshly isolated hFM-MSCs were characterized for their membrane fatty acid composition. hFM-MSCs were cultivated in vitro following a classical protocol and their membrane fatty acid profile at different passages was compared to the profile in vivo. A tailored Refeed® lipid supplement was developed with the aim of reducing the differences created by the in vitro cultivation and was tested on cultured hFM-MSCs. Cell morphology, viability, proliferation, angiogenic differentiation, and immunomodulatory properties after in vitro exposure to the tailored Refeed® lipid supplement were investigated.ResultsA significant modification of hFM-MSC membrane fatty acid composition occurred during in vitro culture. Using a tailored lipid supplement, the fatty acid composition of cultured cells remained more similar to their in vivo counterparts, being characterized by a higher polyunsaturated and omega-6 fatty acid content. These changes in membrane composition had no effect on cell morphology and viability, but were linked with increased cell proliferation rate, angiogenic differentiation, and immunomodulatory properties. In particular, Refeed®-supplemented hFM-MSCs showed greater ability to express fully functional cell membrane molecules.ConclusionsCulturing hFM-MSCs alters their fatty acid composition. A tailored lipid supplement is able to improve in vitro hFM-MSC functional properties by recreating a membrane environment more similar to the physiological counterpart. This approach should be considered in cell therapy applications in order to maintain a higher cell quality during in vitro passaging and to influence the outcome of cell-based therapeutic approaches when cells are administered to patients.
Highlights
The study of lipid metabolism in stem cell physiology has recently raised great interest
Cultured Human fetal membrane mesenchymal stromal cell (hFM-Mesenchymal stromal cell (MSC)) have significantly different membrane fatty acid composition compared to their fresh uncultured counterparts Fresh uncultured hFM-MSCs showed variability in their membrane fatty acid composition, likely due to the genetic and lifestyle diversity of the donors
They had a membrane fatty acid composition mainly characterized by a high omega-6 fatty acid content, which represented more than 25% of total membrane fatty acids
Summary
The study of lipid metabolism in stem cell physiology has recently raised great interest. The development of a fully defined and xeno-free system (i.e., chemically and physically defined) is required in stem/somatic cell culture to provide a “non-contaminated” cell population for cell therapy and tissue regeneration to eliminate safety concerns related to clinical use. In this context, lipid metabolism is pivotal in stem cell physiology and it plays a central role in stem cell maintenance and differentiation [8,9,10]. Kang and co-workers recently reviewed the preliminary efforts produced by the stem cell community in investigating the in vitro regulation of stem cell proliferation and differentiation by essential fatty acids and their metabolites [11]
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