Engineered thoracic spinal cord organoids for transplantation after spinal cord injury

Yanjing Zhu, Ruiqi Huang, Liqun Yu, Zhibo Liu, Yuchen Liu, Wenyong Fan, Gufa Lin, Zhaojie Wang, Xiaolie He, Xu Xu, Bei Ma, Youwei Chen, Yuxin Bai, Jing Li, Bairu Chen, Liming Cheng & Rongrong Zhu

Nature Biomedical Engineering, 24 October 2025 / Volume 10, 2262–2282 (2026)
DOI: https://doi.org/10.1038/s41551-025-01549-8

This Journal Club explores how regional identity and functional integration can be engineered to improve organoid-based spinal cord repair. The study uses a bioactive matrix to generate human spinal cord organoids with thoracic characteristics, which integrate with host tissue and support partial motor recovery after transplantation in mice.
The discussion focuses on matching grafts to the injury site and establishing functional host–graft connections, with implications for combining organoid transplantation with synapse-organizing strategies to enhance circuit reconstruction.

A critical role for microglia in regulating metabolic homeostasis and neural repair after spinal cord injury

Huan Jian, Kailin Wu, Yigang Lv, Jiawei Du, Mengfan Hou, Chi Zhang, Jianqing Gao, Hengxing Zhou, Shiqing Feng

Free Radical Biology and Medicine, 20 November 2024, Volume 225, 469-481
DOI: 10.1016/j.freeradbiomed.2024.10.288

This Journal Club examines how microglia shape the tissue environment for repair after spinal cord injury. The study shows that microglial depletion disrupts lipid metabolism, increases neuronal oxidative stress, and impairs motor recovery.
The discussion focuses on the protective functions of microglia in maintaining metabolic homeostasis, highlighting how preserving these functions could complement strategies aimed at promoting neural regeneration and rebuilding functional connections.

From Organoids to Functional Neural Networks: What Limits Reliability, and How Can We Engineer Toward Intelligence?

Brain organoids reproduce key features of human neural development, yet generating stable and reproducible functional networks remains challenging. This review examines the gap between spontaneous electrical activity and organized network function, focusing on neuronal maturation, batch variability, and synaptic organization. Topics include vascularization and perfusion, the assembly of region-specific organoids into interconnected circuits, and advanced electrophysiological recording technologies. These developments are considered alongside closed-loop stimulation and feedback approaches for investigating learning-like adaptation.
The presentation concludes with an integrated framework linking maturation, circuit assembly, synaptic organization, and functional assessment, highlighting synapse-organizing molecules such as CPTX as potential tools for engineering more reliable and controllable organoid networks.

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Integrating hydrogels manipulate ECM deposition after spinal cord injury for specific neural reconnections via neuronal relays

Zan Tan, Longyou Xiao, Junwu Ma, Kaixi Shi, Jialin Liu, Feng Feng, Pengfei Xie, Yu Dai, Qiuju Yuan, Wutian Wu, Limin Rong, and Liumin He

Science Advances, 3 Jul 2024, Vol 10, Issue 27
DOI: 10.1126/sciadv.ado9120

Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons

Tatsuya Osaki, Tomoya Duenki, Siu Yu A. Chow, Yasuhiro Ikegami, Romain Beaubois, Timothée Levi, Nao Nakagawa-Tamagawa, Yoji Hirano & Yoshiho Ikeuchi
Nat Commun 15, 2945 (2024).
https://doi.org/10.1038/s41467-024-46787-7

Hypothalamic deep brain stimulation augments walking after spinal cord injury.

Cho, N., Squair, J.W., Aureli, V. et al.
Nat Med 30, 3676–3686 (2024).
https://doi.org/10.1038/s41591-024-03306-x