Binder Bernard Y K, Williams Priscilla A, Silva Eduardo A, Leach J Kent
1 Department of Biomedical Engineering, University of California , Davis, Davis, California.
2 Department of Orthopaedic Surgery, School of Medicine, University of California , Davis, Sacramento, California.
Tissue Eng Part B Rev. 2015 Dec;21(6):531-42. doi: 10.1089/ten.TEB.2015.0107. Epub 2015 Jul 14.
The presentation and controlled release of bioactive signals to direct cellular growth and differentiation represents a widely used strategy in tissue engineering. Historically, work in this field has primarily focused on the delivery of large cytokines and growth factors, which can be costly to manufacture and difficult to deliver in a sustained manner. There has been a marked increase over the past decade in the pursuit of lipid mediators due to their wide range of effects over multiple cell types, low cost, and ease of scale-up. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are two bioactive lysophospholipids (LPLs) that have gained attention for use as pharmacological agents in tissue engineering applications. While these lipids can have similar effects on cellular response, they possess distinct chemical backbones, mechanisms of synthesis and degradation, and signaling pathways using a discrete set of G-protein-coupled receptors (GPCRs). LPA and S1P predominantly act extracellularly on their GPCRs and can directly regulate cell survival, differentiation, cytokine secretion, proliferation, and migration--each of the important functions that must be considered in regenerative medicine. In addition to these potent physiological functions, these LPLs play pivotal roles in a number of pathophysiological processes. To capitalize on the promise of these molecules in tissue engineering, these lipids have been incorporated into biomaterials for in vivo delivery. Here, we survey the effects of LPA and S1P on both cellular- and tissue-level phenotypes, with an eye toward regulating stem/progenitor cell growth and differentiation. In particular, we examine work that has translational applications for cell-based tissue engineering strategies in promoting cell survival, bone and cartilage engineering, and therapeutic angiogenesis.
呈现生物活性信号并实现其可控释放以引导细胞生长和分化是组织工程中广泛应用的策略。从历史上看，该领域的工作主要集中在递送大型细胞因子和生长因子，这些因子生产成本高昂且难以持续递送。由于脂质介质对多种细胞类型具有广泛作用、成本低且易于扩大规模，在过去十年中对其的研究显著增加。溶血磷脂酸（LPA）和1-磷酸鞘氨醇（S1P）是两种具有生物活性的溶血磷脂（LPL），在组织工程应用中作为药物制剂受到关注。虽然这些脂质对细胞反应可能有相似的影响，但它们具有不同的化学骨架、合成和降解机制，以及使用一组离散的G蛋白偶联受体（GPCR）的信号通路。LPA和S1P主要在细胞外作用于其GPCR，可直接调节细胞存活、分化、细胞因子分泌、增殖和迁移——这些都是再生医学中必须考虑的重要功能。除了这些强大的生理功能外，这些LPL在许多病理生理过程中也起着关键作用。为了利用这些分子在组织工程中的潜力，已将这些脂质纳入生物材料用于体内递送。在此，我们综述LPA和S1P对细胞和组织水平表型的影响，着眼于调节干/祖细胞的生长和分化。特别是，我们研究了在促进细胞存活、骨和软骨工程以及治疗性血管生成方面对基于细胞的组织工程策略具有转化应用价值的研究。
