3D bioprinting patient-derived induced pluripotent stem cell models of Alzheimer’s disease using a smart bioink

Bioelectronic Medicine

Research Article

Claire Benwood¹  Stephanie M. Willerth²  Jonathan Walters-Shumka³  Kali Scheck³ 

[1] Department of Mechanical Engineering, University of Victoria, V8P 5C2, Victoria, BC, Canada;Department of Mechanical Engineering, University of Victoria, V8P 5C2, Victoria, BC, Canada;Division of Medical Sciences, University of Victoria, V8P 5C2, Victoria, BC, Canada;School of Biomedical Engineering, The University of British Columbia, V6T 1Z3, Vancouver, BC, Canada;Division of Medical Sciences, University of Victoria, V8P 5C2, Victoria, BC, Canada;

关键词: 3D bioprinting;    Microspheres;    Neural tissue;    Bioink;    Stem cells;    Alzheimer’s disease;   

DOI  :  10.1186/s42234-023-00112-7

 received in 2023-03-31, accepted in 2023-05-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAlzheimer’s disease (AD), a progressive neurodegenerative disorder, is becoming increasingly prevalent as our population ages. It is characterized by the buildup of amyloid beta plaques and neurofibrillary tangles containing hyperphosphorylated-tau. The current treatments for AD do not prevent the long-term progression of the disease and pre-clinical models often do not accurately represent its complexity. Bioprinting combines cells and biomaterials to create 3D structures that replicate the native tissue environment and can be used as a tool in disease modeling or drug screening.MethodsThis work differentiated both healthy and diseased patient–derived human induced pluripotent stems cells (hiPSCs) into neural progenitor cells (NPCs) that were bioprinted using the Aspect RX1 microfluidic printer into dome-shaped constructs. The combination of cells, bioink, and puromorphamine (puro)-releasing microspheres were used to mimic the in vivo environment and direct the differentiation of the NPCs into basal forebrain-resembling cholinergic neurons (BFCN). These tissue models were then characterized for cell viability, immunocytochemistry, and electrophysiology to evaluate their functionality and physiology for use as disease-specific neural models.ResultsTissue models were successfully bioprinted and the cells were viable for analysis after 30- and 45-day cultures. The neuronal and cholinergic markers β-tubulin III (Tuj1), forkhead box G1 (FOXG1), and choline acetyltransferase (ChAT) were identified as well as the AD markers amyloid beta and tau. Further, immature electrical activity was observed when the cells were excited with potassium chloride and acetylcholine.ConclusionsThis work shows the successful development of bioprinted tissue models incorporating patient derived hiPSCs. Such models can potentially be used as a tool to screen promising drug candidates for treating AD. Further, this model could be used to increase the understanding of AD progression. The use of patient derived cells also shows the potential of this model for use in personalized medicine applications.

【 授权许可】

CC BY   
© The Author(s) 2023

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