CNS Organoid Surpasses Cell-Laden Microgel Assembly to Promote Spinal Cord Injury Repair

Abstract

The choice of therapeutic agents remains an unsolved issue in the repair of spinal cord injury. In this work, various agents and configurations were investigated and compared for their performance in promoting nerve regeneration, including bead assembly and bulk gel of collagen and Matrigel, under acellular and cell-laden conditions, and cerebral organoid (CO) as the in vitro preorganized agent. First, in Matrigel-based agents and the CO transplantations, the recipient animal gained more axon regeneration and the higher Basso, Beattie, and Bresnahan (BBB) scoring than the grafted collagen gels. Second, new nerves more uniformly infiltrated into the transplants in bead form assembly than the molded chunks. Third, the materials loaded the neural progenitor cells (NPCs) or the CO implantation groups received more regenerated nerve fibers than their acellular counterparts, suggesting the necessity to transplant exogenous cells for large trauma (e.g., a 5 mm long spinal cord transect). In addition, the activated microglial cells might benefit from neural regeneration after receiving CO transplantation in the recipient animals. The organoid augmentation may suggest that in vitro maturation of a microtissue complex is necessary before transplantation and proposes organoids as the premium therapeutic agents for nerve regeneration.

The Progress in Molecular Transport and Therapeutic Development in Human Blood–Brain Barrier Models in Neurological Disorders

“…Matrigel, gelatin, fibronectin, and laminin are possible culture substrates for neural cells (Komura et al 2015 ). Matrigel is a gelatinous, high in various CNS proteins extracellular matrix mixture secreted by Engelbreth-Holm-Swarm mouse sarcoma cells (Berg et al 2018 ; Wang et al 2022 ). This substrate promotes the differentiation of various cell types (Kleinman and Martin 2005 ).…”

3D hydrogel microfibers promote the differentiation of encapsulated neural stem cells and facilitate neuron protection and axon regrowth after complete transactional spinal cord injury

“…After 14 d of in vitro culturing, the SCLT exhibited architectural and phenotypic changes in the adult rat's spinal cord, and significant motor function recovery was achieved after the transplantation of SCLT into the rat SCI model [17]. Furthermore, Wang et al reported that the transplantation of pre-matured cerebral organoids facilitated spinal cord regeneration in SCI [18]. These collective research works indicate that the pre-maturing of NSCs before transplantation can increase neuronal phenotypes and generate better functionality, thus ultimately promoting regeneration effect in vivo.…”