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机械力在器官型模型中引导轴突通过黑质纹状体通路生长。

Mechanical Forces Guide Axon Growth through the Nigrostriatal Pathway in an Organotypic Model.

作者信息

De Vincentiis Sara, Capitanini Elena, Kira Karen, Dell'Amico Claudia, Takahashi Jun, Onorati Marco, Raudzus Fabian, Raffa Vittoria

机构信息

Department of Biology, University of Pisa, Pisa, 56126, Italy.

Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.

出版信息

Adv Sci (Weinh). 2025 Aug;12(31):e2500400. doi: 10.1002/advs.202500400. Epub 2025 May 11.


DOI:10.1002/advs.202500400
PMID:40349175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12376662/
Abstract

Reconstructing the nigrostriatal pathway is one of the major challenges in cell replacement therapies for Parkinson's disease due to the lack of enabling technologies capable of guiding the reinnervation of dopaminergic precursors transplanted into the substantia nigra toward the striatum. This paper examines nano-pulling, as a technology to enable the remote manipulation of axonal growth. Specifically, an organotypic model consisting of co-cultures of the substantia nigra and the striatum is developed to demonstrate that when cortical neural progenitors are transplanted into the substantia nigra, nano-pulling can guide and enhance the elongation of neural projections toward the striatum. To provide additional evidence, induced pluripotent stem cell-derived dopaminergic progenitor neurospheres are generated and it is shown that nano-pulling can induce guided growth and promote the maturation of their neural processes. Altogether, this study demonstrates the potential of nano-pulling as an emerging technique to promote directed reinnervation within the central nervous system.

摘要

重建黑质纹状体通路是帕金森病细胞替代疗法的主要挑战之一,因为缺乏能够引导移植到黑质的多巴胺能前体细胞重新支配纹状体的技术。本文研究了纳米牵拉技术,这是一种能够远程操纵轴突生长的技术。具体而言,构建了一个由黑质和纹状体共培养组成的器官型模型,以证明当将皮质神经祖细胞移植到黑质中时,纳米牵拉可以引导并增强神经突起向纹状体的延伸。为了提供更多证据,生成了诱导多能干细胞来源的多巴胺能祖细胞神经球,结果表明纳米牵拉可以诱导定向生长并促进其神经突起的成熟。总之,本研究证明了纳米牵拉作为一种新兴技术在促进中枢神经系统内定向再支配方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/399dd141090d/ADVS-12-2500400-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/1b17b45b8757/ADVS-12-2500400-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/b21c27afb76e/ADVS-12-2500400-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/3ce6d50a7332/ADVS-12-2500400-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/b4cb4b25982c/ADVS-12-2500400-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/9057b6220d4e/ADVS-12-2500400-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/399dd141090d/ADVS-12-2500400-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/1b17b45b8757/ADVS-12-2500400-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/b21c27afb76e/ADVS-12-2500400-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/3ce6d50a7332/ADVS-12-2500400-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/b4cb4b25982c/ADVS-12-2500400-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/9057b6220d4e/ADVS-12-2500400-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e1/12376662/399dd141090d/ADVS-12-2500400-g001.jpg

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[10]
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本文引用的文献

[1]
Phase I trial of hES cell-derived dopaminergic neurons for Parkinson's disease.

Nature. 2025-5

[2]
Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson's disease.

Nature. 2025-5

[3]
Long-range directional growth of neurites induced by magnetic forces.

Acta Biomater. 2025-1-24

[4]
Nanomagnetic Guidance Shapes the Structure-Function Relationship of Developing Cortical Networks.

Nano Lett. 2024-10-30

[5]
MRI contrast agents and retention in the brain: review of contemporary knowledge and recommendations to the future.

Insights Imaging. 2024-7-25

[6]
Long-Term Mouse Spinal Cord Organotypic Slice Culture as a Platform for Validating Cell Transplantation in Spinal Cord Injury.

J Vis Exp. 2024-4-12

[7]
Nano-pulling stimulates axon regeneration in dorsal root ganglia by inducing stabilization of axonal microtubules and activation of local translation.

Front Mol Neurosci. 2024-4-3

[8]
Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD.

Cell Stem Cell. 2023-10-5

[9]
Microtubules as a signal hub for axon growth in response to mechanical force.

Biol Chem. 2024-1-29

[10]
Recent progress in the effect of magnetic iron oxide nanoparticles on cells and extracellular vesicles.

Cell Death Discov. 2023-6-28

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