Engineering Organoids for in vitro Modeling of Phenylketonuria

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Kerensa Broersen¹  Tiago G. Fernandes²  Alice C. Borges²  Paula Leandro³ 

[1] Department of Applied Stem Cell Technologies, Faculty of Science and Technology, Technical Medical Centre, University of Twente, Enschede, Netherlands;Department of Bioengineering and iBB – Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal;Associate Laboratory i4HB – Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal;Faculty of Pharmacy, iMed.ULisboa - Research Institute for Medicines, Universidade de Lisboa, Lisbon, Portugal;

关键词: phenylketonuria;    human induced pluripotent stem cells;    organoids;    neurodegeneration;    neurodevelopment;    disease modeling;   

DOI  :  10.3389/fnmol.2021.787242

 received in 2021-09-30, accepted in 2021-11-29,  发布年份 2022

来源: Frontiers

【 摘 要 】

Phenylketonuria is a recessive genetic disorder of amino-acid metabolism, where impaired phenylalanine hydroxylase function leads to the accumulation of neurotoxic phenylalanine levels in the brain. Severe cognitive and neuronal impairment are observed in untreated/late-diagnosed patients, and even early treated ones are not safe from life-long sequelae. Despite the wealth of knowledge acquired from available disease models, the chronic effect of Phenylketonuria in the brain is still poorly understood and the consequences to the aging brain remain an open question. Thus, there is the need for better predictive models, able to recapitulate specific mechanisms of this disease. Human induced pluripotent stem cells (hiPSCs), with their ability to differentiate and self-organize in multiple tissues, might provide a new exciting in vitro platform to model specific PKU-derived neuronal impairment. In this review, we gather what is known about the impact of phenylalanine in the brain of patients and highlight where hiPSC-derived organoids could contribute to the understanding of this disease.

【 授权许可】

Unknown   
Copyright © 2022 Borges, Broersen, Leandro and Fernandes.