image: Schematic Diagram of Spinal Cord Injury Repair Promoted by Segment-Specific Human Spinal Cord Neural Stem Cells
Credit: ©Science China Press
Research Background
Spinal cord injury (SCI) causes structural damage to neural circuits, which in turn leads to sensory and motor dysfunction. Transplantation of neural precursor cells/stem cells provides a potential therapeutic strategy for reconstructing damaged neural circuits and promoting SCI repair. Previous studies by the team led by Professor Jianwu Dai from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (CAS), have shown that spinal cord-derived neural stem cells exhibit significant tissue-specific advantages in promoting SCI repair compared to brain-derived neural stem cells and embryonic stem cell-derived neural stem cells. This finding provides an important theoretical basis for the application of tissue-specific stem cells in regenerative medicine. Notably, during early spinal cord development, neural precursor cells in different anatomical segments along the rostrocaudal axis differentiate into neuron subsets with regional specificity. These specifically differentiated cells participate in motor regulation by establishing precise neural connections. However, a key scientific question—whether neural stem cells derived from different spinal cord segments (such as cervical, thoracic, and lumbar segments) differ in their repair efficacy after injury—remains to be clarified. Deciphering the differences in regenerative properties of neural stem cells from different segments is of great clinical significance for optimizing cell transplantation strategies and achieving precise neural repair.
Research Content and Main Achievements
Professor Jianwu Dai and Professor Yannan Zhao from the Institute of Genetics and Developmental Biology, CAS, collaborated with Professor Xia Wang from the School of Pharmaceutical Sciences, Tsinghua University, to systematically analyze the segment-specific biological characteristics of human cervical, thoracic, and lumbar spinal cord neural stem cells (hscNSCs), and for the first time clarify the differences in repair efficacy of hscNSCs from different segments in the SCI microenvironment.
The research team independently developed a culture system for human embryonic spinal cord neural stem cells (hscNSCs), successfully achieving efficient expansion of hscNSCs from cervical, thoracic, and lumbar segments. Through multi-omics analysis, they found that hscNSCs from different segments exhibit significantly different transcriptional profiles and differentiation fate tendencies. Mechanistic studies showed that thoracic hscNSCs specifically express high levels of hepatocyte growth factor (HGF), a property derived from their retention of the molecular memory of preganglionic motor column neuronal precursor cells in the thoracic spinal cord during development. In rat models of thoracic SCI, the thoracic hscNSC transplantation group showed significant advantages: their survival rate was significantly higher than that of cells derived from cervical and lumbar segments, the efficiency of neural axon regeneration was significantly increased, and the inflammatory response was effectively inhibited by regulating the injury microenvironment, while the area of fibrotic scarring was significantly reduced. Functional evaluation showed that the motor function scores of animals that received thoracic hscNSC transplantation were significantly higher than those of the control group.
Significance or Potential Value of the Article and Research Achievements
Entitled "Spinal Segment-specific Properties of Neural Stem Cells Contribute to the Outcomes of Spinal Cord Injury Repair", this study was recently published in the journal Science China Life Sciences. From the perspective of developmental biology, the study clarifies the segmental heterogeneity of human spinal cord neural stem cells. It not only provides a new perspective for understanding the mechanism of spinal cord regionalized development, but more importantly, establishes a new "anatomical segment-matched" stem cell transplantation strategy. This precise treatment paradigm based on the specificity of developmental origin opens a new path for breaking through the bottleneck of clinical translation in SCI repair, and promotes spinal cord regenerative repair towards personalized and precise treatment.
Journal
Science China Life Sciences