Metabolic Reprogramming of Neural Stem Cells by Chiral Nanofiber for Spinal Cord Injury
Haining Wu, Chao Xing, Beibei Yu, Lingli Guo, Xiaoqiu Dou, Laiben Gao, Shijie Yang, Yongfeng Zhang, Xue Gao, Shengyou Li, Bing Xia, Teng Ma, Yiming Hao, Yujie Yang, Xueli Gao, Yitao Wei, Borui Xue, Qing Zhang, Chuanliang Feng, Jinghui Huang
Abstract
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.