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Construct spinal cord-like white matter to promote straight axon growth and myelination, repair spinal cord injury

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Studies have found that simple cell transplantation is difficult to achieve targeted differentiation of stem cells into functional cells in the complex microenvironment of spinal cord injury. The advantage of the tissue engineering strategy is that it can design the optimal combination of scaffold materials, seed cells and biologically active factors according to the specific needs of spinal cord repair to deal with the key scientific problems of reshaping the nerve regeneration microenvironment and repairing the spinal cord nerve circuit.

The team of Professor Yuanshan Zeng of Sun Yat-sen University has long been committed to applying stem cells and tissue engineering strategies to repair the nerve circuits of the injured spinal cord. Based on the need to promote the straight growth of spinal white matter axons and the formation of myelin sheaths, the team’s researchers have adopted the concept of synthetic biology And tissue engineering new technology, designed and constructed spinal cord-like white matter tissue (like white matter).

The construction of white matter integrates the interaction of four important factors: natural bioactive scaffolds, seed cells, neurotrophic factors and culture time. Among them, the choice of natural bioactive scaffold is a key factor. Although injectable gel materials or nano/micron-scale particles can fill the syringomyelia and promote axon growth, for large-scale defect injuries, directing the axon to regenerate requires the scaffold material to be straight-oriented.

Researchers have found that decellularized optic nerve can be used as the preferred material for the construction of spinal cord white matter. This natural bioactive scaffold is characterized by its microtopological physical structure, that is, evenly distributed straight channels and micron-level horizontal pores, which are particularly suitable for the straight growth of regenerated axons and their lateral buds, as well as the creation of oligodendrocytes. Space for migration and information exchange between channels. Another feature is that the unique extracellular matrix of the decellularized optic nerve can provide a more suitable microenvironment for the colonization, differentiation and functional maturation of the oligodendrocyte lineage. The proteomics test results and the analysis of single cell sequencing of the oligodendrocyte lineage confirmed an important mechanism for the decellularized optic nerve to induce the development and functional maturation of the oligodendrocyte lineage.

The construction of WMLT and its transplantation to repair the hemi-transverse dorsal spinal cord injury in rats

Studies have found that the white matter constructed by decellularized optic nerves has achieved good integration with the white matter of the host spinal cord, allowing the regenerated axons to grow straight and myelinate, and promote significant improvements in the fine motor and sensory functions of the limbs. Leukocyte-like tissue transplantation provides physical guidance, extracellular matrix, myelin forming cells and neurotrophic factors for regenerating axons. Interestingly, laminin (LN), which is rich in decellularized optic nerves, can bind to neurotrophin-3 (NT-3) secreted by oligodendrocytes, creating a localized The microenvironment enriched in NT-3 can better maintain the unique niche that promotes nerve regeneration and myelination.

The research results were recently published in the journal Bioactive Materials. This study provides a new tissue engineering strategy for efficiently repairing spinal cord white matter injury. In future research, the patient’s autologous iPSC-derived neural stem cells can be planted on a decellularized optic nerve scaffold derived from humanized gene-edited pigs to construct a spinal cord-like tissue that can be used in clinics. Tissue engineering design strategies can also be adopted to load the decellularized optic nerve. Other types of functional seed cells, or modified the decellularized optic nerve function, are used to construct tissue-engineered tissues or organoids to meet the needs of in vitro pathology and drug research models or to meet the needs of in vivo transplantation and repair of damaged tissues need.

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