Huang Biao, Zeng Zipeng, Zhang Chennan C, Schreiber Megan E, Li Zhongwei
USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Front Cell Dev Biol. 2022 Jul 22;10:953408. doi: 10.3389/fcell.2022.953408. eCollection 2022.
One out of seven people develop chronic kidney disease (CKD). When kidney function continues to decline, CKD patients may develop end-stage renal disease (ESRD, or kidney failure). More than 2 out of 1,000 adults develop ESRD and these patients must live on dialysis or get a kidney transplant to survive. Each year, more than $51 billion is spent to treat patients with ESRD in the United States. In addition, ESRD greatly reduces longevity and quality of life for patients. Compared to dialysis, kidney transplant offers the best chance of survival, but few donor organs are available. Thus, there is an urgent need for innovative solutions that address the shortage of kidneys available for transplantation. Here we summarize the status of current approaches that are being developed to solve the shortage of donor kidneys. These include the bioartificial kidney approach which aims to make a portable dialysis device, the recellularization approach which utilizes native kidney scaffold to make an engineered kidney, the stem cell-based approach which aims to generate a kidney by recapitulating normal kidney organogenesis, the xenotransplantation approach which has the goal to make immunocompatible pig kidneys for transplantation, and the interspecies chimera approach which has potential to generate a human kidney in a host animal. We also discuss the interconnections among the different approaches, and the remaining challenges of translating these approaches into novel therapies.
七分之一的人会患上慢性肾脏病(CKD)。当肾功能持续下降时,CKD患者可能会发展为终末期肾病(ESRD,即肾衰竭)。每1000名成年人中就有超过2人会发展为ESRD,这些患者必须依靠透析或接受肾脏移植才能存活。在美国,每年花费超过510亿美元来治疗ESRD患者。此外,ESRD极大地缩短了患者的寿命并降低了其生活质量。与透析相比,肾脏移植提供了最佳的生存机会,但可用的供体器官很少。因此,迫切需要创新的解决方案来解决可用于移植的肾脏短缺问题。在此,我们总结了目前正在开发的解决供体肾脏短缺问题的方法的现状。这些方法包括旨在制造便携式透析设备的生物人工肾方法、利用天然肾脏支架制造工程肾脏的再细胞化方法、旨在通过重现正常肾脏器官发生过程来生成肾脏的基于干细胞的方法、旨在制造用于移植的免疫相容性猪肾脏的异种移植方法以及有可能在宿主动物体内生成人类肾脏的种间嵌合体方法。我们还讨论了不同方法之间的相互联系,以及将这些方法转化为新疗法所面临的剩余挑战。