Bioactive Spinal Cord Scaffold Releasing Neurotrophic Exosomes to Promote In Situ Centralis Neuroplasticity

Abstract

Spinal cord injury (SCI), one of the most serious injuries of the central nervous system, causes physical functional dysfunction and even paralysis in millions of patients. As a matter of necessity, redressing the neuroleptic pathologic microenvironment to a neurotrophic microenvironment is essential in order to alleviate this dilemma and facilitate the recovery of the spinal cord. Herein, based on cell-sheet technology, two functional cell types�uninduced and neural-induced stem cells from human exfoliated deciduous teeth�were formed into a composite membrane that subsequently self-assembled to form a bioactive scaffold with a spinal-cord-like structure, called a spinal cord assembly (SCA). In a stable extracellular matrix microenvironment, SCA continuously released SCA-derived exosomes containing various neurotrophic factors, which effectively promoted neuronal regeneration, axonal extension, and angiogenesis and inhibited glial scar generation in a rat model of SCI. Neurotrophic exosomes significantly improved the pathological microenvironment and promoted in situ centralis neuroplasticity, ultimately eliciting a strong repair effect in this model. SCA therapy is a promising strategy for the effective treatment of SCI based on neurotrophic exosome delivery.

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization

“…10 Sisi Mi and others prepared a neuron-dense 2D membrane with human exfoliated deciduous teeth stem cell (SHED)-induced neurons, capable of secreting ECM and exosomes. 41 Utilizing the cell sheet technique, they combined the 2D membrane with uninduced stem cells, mechanically curling them into a cylindrical shape to form a spinal cord assemblage. 41 However, this model only mimicked the cylindrical appearance of the spinal cord and contained a fraction of neurons.…”

“…41 Utilizing the cell sheet technique, they combined the 2D membrane with uninduced stem cells, mechanically curling them into a cylindrical shape to form a spinal cord assemblage. 41 However, this model only mimicked the cylindrical appearance of the spinal cord and contained a fraction of neurons. 41 Many cavities inevitably arise from mechanical folding, and the neuron distribution was entirely different from the cellular partitioning of the natural spinal cord.…”

“…41 However, this model only mimicked the cylindrical appearance of the spinal cord and contained a fraction of neurons. 41 Many cavities inevitably arise from mechanical folding, and the neuron distribution was entirely different from the cellular partitioning of the natural spinal cord. Bai Xu and others induced hscNPCs implanted on collagen scaffolds into dorsal and ventral spinal cord organoids (DVs, SCs) in vitro using different induction protocols and mechanically assembled them, resulting in engineered human embryonic spinal cord-like tissue (DV-SC) with dorsal and ventral neuronal features.…”

“…Degradation products, side chain groups, unreacted groups, or initiators needed for gel formation in synthetic hydrogels can be cytotoxic, limiting their application in organoid culture . Sisi Mi and others prepared a neuron-dense 2D membrane with human exfoliated deciduous teeth stem cell (SHED)-induced neurons, capable of secreting ECM and exosomes . Utilizing the cell sheet technique, they combined the 2D membrane with uninduced stem cells, mechanically curling them into a cylindrical shape to form a spinal cord assemblage .…”

The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives

“…These systems, such as hydrogel-loaded exosomes, have shown encouraging therapeutic effects and find extensive applications in the fields of tissue repair and regenerative medicine. 121 , 122 Plant-derived exosomes have gained increasing attention in recent years due to their plentiful sources and lower immunogenicity when compared to exosomes derived from mammals. Another advantage of plant-derived exosomes is their absence of zoonotic or human pathogens.…”