Restored in vivo-like membrane lipidomics positively influence in vitro features of cultured mesenchymal stromal/stem cells derived from human placenta.
Restored in vivo-like membrane lipidomics positively influence in vitro features of cultured mesenchymal stromal/stem cells derived from human placenta.
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DOI：
10.1186/s13287-017-0487-4
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发表时间：
2017-02-07
影响因子：
7.5
通讯作者：
Bonsi L
中科院分区：
文献类型：
--
作者：
Chatgilialoglu A;Rossi M;Alviano F;Poggi P;Zannini C;Marchionni C;Ricci F;Tazzari PL;Taglioli V;Calder PC;Bonsi L
近年来，干细胞生理学中脂质代谢的研究引起了人们极大的兴趣。脂质的作用不仅仅是组装细胞外和细胞内隔室的结构参与。尽管如此，我们仍然远远没有理解膜脂质组学在干细胞维持和分化模式中的影响。在过去的几年中，已经报道了体外细胞培养如何改变膜脂质组学。本工作的目的是研究来源于人胎膜的间充质基质细胞（MSC）（hFM-MSC）的膜脂肪酸谱，并通过使用化学定义的定制脂质补充剂（Refeed®）将其与特定的生物学特性相关联。新鲜分离的hFM-MSC的特征在于其膜脂肪酸组成。hFM-MSC在体外培养后，一个经典的协议和他们的膜脂肪酸谱在不同的代次进行了比较，在体内的配置文件。开发了定制的Refeed®脂质补充剂，目的是减少体外培养产生的差异，并在培养的hFM-MSC上进行测试。研究了体外暴露于定制的Refeed®脂质补充剂后的细胞形态、活力、增殖、血管生成分化和免疫调节特性。在体外培养过程中，hFM-MSC膜脂肪酸组成发生了显着的变化。使用定制的脂质补充剂，培养细胞的脂肪酸组成与其体内对应物保持更相似，其特征在于更高的多不饱和脂肪酸和ω-6脂肪酸含量。这些膜组成的变化对细胞形态和活力没有影响，但与细胞增殖率增加、血管生成分化和免疫调节特性有关。特别地，补充有Refeed®的hFM-MSC显示出更大的表达全功能细胞膜分子的能力。培养hFM-MSC改变其脂肪酸组成。定制的脂质补充剂能够通过重建更类似于生理对应物的膜环境来改善体外hFM-MSC功能特性。在细胞治疗应用中应考虑这种方法，以便在体外传代期间保持更高的细胞质量，并在向患者施用细胞时影响基于细胞的治疗方法的结果。
The 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®). Freshly 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. A 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. Culturing 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.