Engineered microtissue as an anatomically inspired model of Parkinson's disease

Although traditional small animal and cell culture models of neurodegenerative disease have been valuable in foundational discoveries, their inherent imprecision may have biased our understanding of etiology in humans and hindered translation of therapeutics. Recent breakthroughs to generate human stem cell–derived brain organoids — including from patient-specific cell sources — provide powerful platforms to improve disease modeling accuracy. However, brain organoids do not recapitulate crucial anatomical structures such as long bundled axon tracts — a central systems-level feature of human brains — critical to neurodegenerative disease pathogenesis, including Parkinson's disease. To address this challenge, advances in tissue engineering recapitulate brain pathways with three-dimensional anatomical fidelity to discrete systems-level brain structures, such as the first tissue engineered nigrostriatal pathway. Promulgating anatomically inspired human-derived engineered microtissue may improve translational relevance, empower personalized medicine, and ultimately reduce costs compared to conventional model systems, thus proving useful for targeted development and screening of new therapeutic strategies.