1 Department of Chemical Engineering, Brigham Young University , Provo, Utah.
2 Department of Genetics and Biotechnology, Brigham Young University , Provo, Utah.
Tissue Eng Part B Rev. 2016 Oct;22(5):358-370. doi: 10.1089/ten.TEB.2015.0520. Epub 2016 Mar 31.
Chronic kidney diseases affect thousands of people worldwide. Although hemodialysis alleviates the situation by filtering the patient's blood, it does not replace other kidney functions such as hormone release or homeostasis regulation. Consequently, orthotopic transplantation of donor organs is the ultimate treatment for patients suffering from end-stage renal failure. Unfortunately, the number of patients on the waiting list far exceeds the number of donors. In addition, recipients must remain on immunosuppressive medications for the remainder of their lives, which increases the risk of morbidity due to their weakened immune system. Despite recent advancements in whole organ transplantation, 40% of recipients will face rejection of implanted organs with a life expectancy of only 10 years. Bioengineered patient-specific kidneys could be an inexhaustible source of healthy kidneys without the risk of immune rejection. The purpose of this article is to review the pros and cons of several bioengineering strategies used in recent years and their unresolved issues. These strategies include repopulation of natural scaffolds with a patient's cells, de-novo generation of kidneys using patient-induced pluripotent stem cells combined with stepwise differentiation, and the creation of a patient's kidney in the embryos of other mammalian species.
慢性肾脏疾病影响着全球成千上万的人。虽然血液透析通过过滤患者的血液来缓解病情,但它并不能替代其他肾脏功能,如激素释放或体内平衡调节。因此,同种异体移植供体器官是终末期肾衰竭患者的最终治疗方法。不幸的是,等待名单上的患者人数远远超过了捐赠者的人数。此外,受者必须在余生中继续服用免疫抑制药物,这增加了因免疫系统减弱而患病的风险。尽管近年来在整个器官移植方面取得了进展,但 40%的受者将面临植入器官的排斥反应,预期寿命仅为 10 年。生物工程化的患者特异性肾脏可以成为健康肾脏的无尽来源,而不会有免疫排斥的风险。本文的目的是回顾近年来使用的几种生物工程策略的优缺点及其未解决的问题。这些策略包括用患者的细胞重新填充天然支架、使用患者诱导多能干细胞结合逐步分化生成新的肾脏,以及在其他哺乳动物胚胎中创建患者的肾脏。