Figliuzzi Marina, Remuzzi Giuseppe, Remuzzi Andrea
IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
Nephron Exp Nephrol. 2014;126(2):113. doi: 10.1159/000360683. Epub 2014 May 19.
Chronic kidney disease (CKD) is a global public health issue with an estimated prevalence of 8-16% worldwide. End-stage renal disease eventually develops every year in 0.15-0.2% of patients with overt CKD, and renal replacement therapy (RRT) with dialysis or transplantation is required. Although approximately 2 million people worldwide are currently on RRT to sustain life, this likely represents less than 10% of those who need it. The kidney transplant approach is also seriously impaired by limited graft survival and by the scarce availability of donors. Innovative tissue-engineering strategies have been recently proposed to overcome these challenges. It is anticipated that these novel approaches will also be cost-effective in the long term. Although the initial setup of these innovative technologies could be quite expensive, there would be a single application for each patient, with no additional costs thereafter, compared to the lifelong costs of dialysis or immunosuppressive medications required for transplantation. One of the most innovative tools currently being investigated in experimental models is based on the idea of using decellularized kidneys to engineer a new functional organ as a potential future treatment option for end-stage renal disease.
In the last 5 years, several interesting observations have been reported regarding the possibility of using an acellular matrix from the whole kidney and the attempt to recellularize this scaffold using stem or differentiated cells. This review provides an overview of the decellularization methods tested so far and their effects on the resulting extracellular matrix structure and composition. In addition, we also discuss methods recently described by us and others for the perfusion of kidney scaffolds for recellularization.
Despite difficulties in achieving the import goal of kidney engineering in the laboratory, we discuss the problems with and limits of the experimental results obtained so far and point out the strategies that need to be adopted in order for this line of research to advance.
慢性肾脏病(CKD)是一个全球性公共卫生问题,全球估计患病率为8%-16%。每年有0.15%-0.2%的显性CKD患者最终发展为终末期肾病,需要进行透析或移植等肾脏替代治疗(RRT)。尽管目前全球约有200万人正在接受RRT以维持生命,但这可能不到需要者的10%。肾移植方法也因移植物存活率有限和供体稀缺而受到严重影响。最近有人提出创新的组织工程策略来克服这些挑战。预计这些新方法从长远来看也将具有成本效益。虽然这些创新技术的初始设置可能相当昂贵,但与透析的终身成本或移植所需的免疫抑制药物相比,每个患者只需单次应用,此后无需额外费用。目前在实验模型中研究的最具创新性的工具之一是基于使用脱细胞肾脏来构建一个新的功能器官,作为终末期肾病未来潜在治疗选择的想法。
在过去5年中,已有几项关于使用全肾脱细胞基质以及尝试用干细胞或分化细胞使该支架重新细胞化可能性的有趣观察报告。本综述概述了迄今为止测试的脱细胞方法及其对所得细胞外基质结构和组成的影响。此外,我们还讨论了我们和其他人最近描述的用于灌注肾脏支架以进行重新细胞化的方法。
尽管在实验室中实现肾脏工程的重要目标存在困难,但我们讨论了迄今为止获得的实验结果存在的问题和局限性,并指出为推动这一研究方向需要采取的策略。