Luka Varda, Tadej Petreski, Lidija Gradišnik, Uroš Maver, Sebastjan Bevc
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引用次数: 0
摘要
肾脏疾病是导致全球死亡的主要原因之一。随着需要住院治疗的急性肾损伤(AKI)发病率不断上升,我们需要更好地了解病理生理机制,以便更有效地治疗患者。肾毒性是导致急性肾损伤的最常见原因之一,这主要是由于非处方药和天然保健品的大量供应,而非处方药和天然保健品可能会在药代动力学等层面与处方药发生相互作用。后者可导致临床相关并发症(包括 AKI),而随着西方国家人口老龄化的加剧以及相关的多种药物的增加,这种并发症就更加明显了。药物测试始于临床前水平,需要一个可靠的模型来足够准确地预测人体对测试药物的反应。最近,人们创建了不同复杂程度的体外肾脏模型来研究肾脏疾病的各个方面。由于近端肾小管在多种机制中发挥着重要作用,因此许多模型都包括近端肾小管上皮细胞(PTECs)。单培养的近端肾小管上皮细胞不足以准确代表体内组织。因此,人们正在建立包含更多细胞类型的更复杂模型。据我们所知,这是第一篇关于共培养模型和细胞类型的综述,这些模型和细胞类型与 PTECs 一起用于研究药物的肾毒性以及 AKI 和慢性肾病(CKD)的其他机制。
Narrative review of proximal tubular epithelial cellin-vitroco-culture models.
Kidney diseases are among the leading causes of death globally. With the increasing rates of acute kidney injury (AKI) requiring hospitalisation, a better understanding of pathophysiological mechanisms is needed to treat the patients more efficiently. Nephrotoxicity is one of the most common causes of AKI, mainly due to the high availability of over-the-counter drugs and natural supplements, which may interact with prescribed drugs at the level of pharmacokinetics, among other factors. The latter can lead to clinically relevant complications (including AKI), which is even more pronounced given the increasingly ageing population in the Western world and the associated increase in polypharmacy. Drug testing starts at the preclinical level, where a reliable model is needed to predict human response to a tested drug with sufficient accuracy. Recently,in-vitrokidney models of different complexities have been created to study various aspects of kidney diseases. Because the proximal tubule plays a vital role in several mechanisms, many models include proximal tubular epithelial cells (PTECs). Monocultures of PTECs do not representin-vivotissue accurately enough. Therefore, more complex models with more cell types are being built. To our knowledge, this is the first review focusing on co-culture models and cell types used alongside PTECs for studying the nephrotoxicity of drugs and other mechanisms of AKI and chronic kidney disease.
期刊介绍:
Biofabrication is dedicated to advancing cutting-edge research on the utilization of cells, proteins, biological materials, and biomaterials as fundamental components for the construction of biological systems and/or therapeutic products. Additionally, it proudly serves as the official journal of the International Society for Biofabrication (ISBF).