Metabolic Reprogramming of Neural Stem Cells by Chiral Nanofiber for Spinal Cord Injury
Exogenous neural stem cells (NSCs) have great potential to reconstitute damage spinal neural circuitry. However, regulating the metabolic reprogramming of NSCs for reliable nerve regeneration has been challenging. This report discusses the biomimetic dextral hydrogel (DH) with right-handed nanofibers that specifically reprograms the lipid metabolism of NSCs, promoting their neural differentiation and rapid regeneration of damaged axons. The underlying mechanism is the intrinsic stereoselectivity between DH and fatty acid-binding protein 5 (FABP5), which facilitates the transportation of fatty acids bound to FABP5 into the mitochondria and endoplasmic reticulum, subsequently augmenting fatty acid oxidation (FAO) levels and enriching sphingosine biosynthesis. In the rat SCI model, DH significantly improved the Basso-Beattie-Bresnahan (BBB) locomotor scores (over 3-fold) and the hindlimbs' compound muscle action potential (over 4-fold) compared with the untreated group, conveying a significant return of functional recovery. This finding of nanoscale chirality-dependent NSCs metabolic reprogramming provides insights into understanding stem cell physiology and presents opportunities for regenerative medicine.
Authors
- Jinghui Huang (ORCID: https://orcid.org/0000-0002-0991-0591)
- Yujie Yang (ORCID: https://orcid.org/0000-0003-3530-4322)
- Beibei Yu (ORCID: https://orcid.org/0000-0002-9076-5597)
- Xue Gao (ORCID: https://orcid.org/0000-0003-3213-9704)
- Yiming Hao (ORCID: https://orcid.org/0000-0001-9374-2369)
- Borui Xue
- Shengyou Li (ORCID: https://orcid.org/0000-0003-3739-2477)
- Xiaoqiu Dou (ORCID: https://orcid.org/0000-0001-5551-965X)
- Laiben Gao (ORCID: https://orcid.org/0000-0003-0335-4675)
- Chuanliang Feng (ORCID: https://orcid.org/0000-0001-6137-5568)
- Lingli Guo (ORCID: https://orcid.org/0000-0003-2529-110X)
- Shijie Yang
- Yitao Wei
- Haining Wu (ORCID: https://orcid.org/0000-0002-5584-5196)
- Bing Xia (ORCID: https://orcid.org/0000-0002-9178-5493)
- Yongfeng Zhang (ORCID: https://orcid.org/0000-0001-7219-8835)
- Chao Xing (ORCID: https://orcid.org/0000-0002-1838-0502)
- Teng Ma (ORCID: https://orcid.org/0000-0001-6070-9976)
- Xueli Gao
- Qing Zhang (ORCID: https://orcid.org/0000-0003-2028-1447)
Institutions
- Shanghai Jiao Tong University (CN)
- Metal Matrix Cast Composites (United States) (US)
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Xijing Hospital (CN)
- Xi'an Jiaotong University (CN)
- Air Force Medical University (CN)
Publication Details
- Journal
- ACS Nano
- Published
- 2025-01-22
- DOI
- https://doi.org/10.1021/acsnano.4c15770
- Citations
- 10
- Primary Topic
- Nerve injury and regeneration
- Type
- article
- Field-Weighted Citation Impact
- 9.09
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials
- National Key Research and Development Program of China