Understanding Immune-Driven Brain Aging by Human Brain Organoid Microphysiological Analysis Platform

被引：43
作者：
Ao, Zheng [1 ]
Song, Sunghwa [1 ]
Tian, Chunhui [1 ]
Cai, Hongwei [1 ]
Li, Xiang [1 ]
Miao, Yifei [2 ,3 ]
Wu, Zhuhao [1 ]
Krzesniak, Jonathan [1 ]
Ning, Bo [4 ]
Gu, Mingxia [2 ,3 ]
Lee, Luke P. [5 ,6 ,7 ]
Guo, Feng [1 ]
机构：
[1] Indiana Univ, Dept Intelligent Syst Engn, Bloomington, IN 47405 USA
[2] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Div Pulm Biol, Ctr Stem Cell & Organoid Med CuSTOM, Cincinnati, OH 45229 USA
[3] Univ Cincinnati, Sch Med, Cincinnati, OH 45229 USA
[4] Tulane Univ, Sch Med, Dept Biochem & Mol Biol, Ctr Cellular & Mol Diagnost, New Orleans, LA 70112 USA
[5] Harvard Univ, Brigham & Womens Hosp, Harvard Med Sch, Harvard Inst Med, Boston, MA 02115 USA
[6] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Dept Bioengn, Berkeley, CA 94720 USA
[7] Sungkyunkwan Univ, Inst Quantum Biophys, Dept Biophys, Suwon 16419, Gyeonggi Do, South Korea
来源：
ADVANCED SCIENCE | 2022年 / 9卷 / 27期
关键词：
aging; brain organoid; inflammaging; microfluidics; neuroimmune interaction; ON-A-CHIP; MONOCYTES; TISSUE; INFLAMMATION; DEFICIENCY; GENERATION; CYTOKINES; PATHWAYS; SCAFFOLD;
D O I：
10.1002/advs.202200475
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
The aging of the immune system drives systemic aging and the pathogenesis of age-related diseases. However, a significant knowledge gap remains in understanding immune-driven aging, especially in brain aging, due to the limited current in vitro models of neuroimmune interaction. Here, the authors report the development of a human brain organoid microphysiological analysis platform (MAP) to discover the dynamic process of immune-driven brain aging. The organoid MAP is created by 3D printing that confines organoid growth and facilitates cell and nutrition perfusion, promoting organoid maturation and their committment to forebrain identity. Dynamic rocking flow is incorporated into the platform that allows to perfuse primary monocytes from young (20 to 30-year-old) and aged (>60-year-old) donors and culture human cortical organoids to model neuroimmune interaction. The authors find that the aged monocytes increase infiltration and promote the expression of aging-related markers (e.g., higher expression of p16) within the human cortical organoids, indicating that aged monocytes may drive brain aging. The authors believe that the organoid MAP may provide promising solutions for basic research and translational applications in aging, neural immunological diseases, autoimmune disorders, and cancer.
引用
收藏
页数：10
相关论文
共 67 条
[1]   Evaluation of cancer immunotherapy using mini-tumor chips [J].
Ao, Zheng ;
Cai, Hongwei ;
Wu, Zhuhao ;
Hu, Liya ;
Li, Xiang ;
Kaurich, Connor ;
Gu, Mingxia ;
Cheng, Liang ;
Lu, Xin ;
Guo, Feng .
THERANOSTICS, 2022, 12 (07) :3628-3636
[2]   Rapid Profiling of Tumor-Immune Interaction Using Acoustically Assembled Patient-Derived Cell Clusters [J].
Ao, Zheng ;
Wu, Zhuhao ;
Cai, Hongwei ;
Hu, Liya ;
Li, Xiang ;
Kaurich, Connor ;
Chang, Jackson ;
Gu, Mingxia ;
Liang, Cheng ;
Lu, Xin ;
Guo, Feng .
ADVANCED SCIENCE, 2022, 9 (22)
[3]   Human Spinal Organoid-on-a-Chip to Model Nociceptive Circuitry for Pain Therapeutics Discovery [J].
Ao, Zheng ;
Cai, Hongwei ;
Wu, Zhuhao ;
Krzesniak, Jonathan ;
Tian, Chunhui ;
Lai, Yvonne Y. ;
Mackie, Ken ;
Guo, Feng .
ANALYTICAL CHEMISTRY, 2022, 94 (02) :1365-1372
[4]   Tubular human brain organoids to model microglia-mediated neuroinflammation [J].
Ao, Zheng ;
Cai, Hongwei ;
Wu, Zhuhao ;
Song, Sunghwa ;
Karahan, Hande ;
Kim, Byungwook ;
Lu, Hui-Chen ;
Kim, Jungsu ;
Mackie, Ken ;
Guo, Feng .
LAB ON A CHIP, 2021, 21 (14) :2751-2762
[5]   Controllable fusion of human brain organoids using acoustofluidics [J].
Ao, Zheng ;
Cai, Hongwei ;
Wu, Zhuhao ;
Ott, Jonathan ;
Wang, Huiliang ;
Mackie, Ken ;
Guo, Feng .
LAB ON A CHIP, 2021, 21 (04) :688-699
[6]   Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo [J].
Arlotta, P ;
Molyneaux, BJ ;
Chen, J ;
Inoue, J ;
Kominami, R ;
Macklis, JD .
NEURON, 2005, 45 (02) :207-221
[7]   High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays [J].
Brandenberg, Nathalie ;
Hoehnel, Sylke ;
Kuttler, Fabien ;
Homicsko, Krisztian ;
Ceroni, Camilla ;
Ringel, Till ;
Gjorevski, Nikolce ;
Schwank, Gerald ;
Coukos, George ;
Turcatti, Gerardo ;
Lutolf, Matthias P. .
NATURE BIOMEDICAL ENGINEERING, 2020, 4 (09) :863-+
[8]   Recapitulating macro-scale tissue self-organization through organoid bioprinting [J].
Brassard, Jonathan A. ;
Nikolaev, Mike ;
Huebscher, Tania ;
Hofer, Moritz ;
Lutolf, Matthias P. .
NATURE MATERIALS, 2021, 20 (01) :22-29
[9]   Intelligent acoustofluidics enabled mini-bioreactors for human brain organoids [J].
Cai, Hongwei ;
Ao, Zheng ;
Wu, Zhuhao ;
Song, Sunghwa ;
Mackie, Ken ;
Guo, Feng .
LAB ON A CHIP, 2021, 21 (11) :2194-2205
[10]   Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease [J].
Cai, Hongwei ;
Ao, Zheng ;
Moon, Younghye ;
Wu, Zhuhao ;
Lu, Hui-Chen ;
Kim, Jungsu ;
Guo, Feng ;
Hu, Liya .
ANALYST, 2020, 145 (19) :6243-6253
1234567