A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord

Abstract

Tissue engineering–based neural construction holds promise in providing organoids with defined differentiation and therapeutic potentials. Here, a bioengineered transplantable spinal cord–like tissue (SCLT) is assembled in vitro by simulating the white matter and gray matter composition of the spinal cord using neural stem cell–based tissue engineering technique. Whether the organoid would execute targeted repair in injured spinal cord is evaluated. The integrated SCLT, assembled by white matter–like tissue (WMLT) module and gray matter–like tissue (GMLT) module, shares architectural, phenotypic, and functional similarities to the adult rat spinal cord. Organotypic coculturing with the dorsal root ganglion or muscle cells shows that the SCLT embraces spinal cord organogenesis potentials to establish connections with the targets, respectively. Transplantation of the SCLT into the transected spinal cord results in a significant motor function recovery of the paralyzed hind limbs in rats. Additionally, targeted spinal cord tissue repair is achieved by the modular design of SCLT, as evidenced by an increased remyelination in the WMLT area and an enlarged innervation in the GMLT area. More importantly, the pro‐regeneration milieu facilitates the formation of a neuronal relay by the donor neurons, allowing the conduction of descending and ascending neural inputs.

Electroacupuncture Facilitates the Integration of Neural Stem Cell-Derived Neural Network with Transected Rat Spinal Cord

“…Basically, following general anesthesia and exposure of the sensorimotor cortex (SMC) and sciatic nerves, the electrodes (NeuroExam M-800 Data Acquisition Analysis System, MEDCOM, Zhuhai, China) were connected to the SMC and sciatic nerve, respectively. When detecting the CMEP, the stimulating electrodes (active silver midline epidural electrodes) were placed in the SMC (located 2 mm lateral to midline and 2 mm caudal to bregma) and the recording electrodes were connected with the sciatic nerve according to our previous study (Lai et al., 2018). Fifty response waveforms of CMEP and SSEP were collected and averaged for each rat with stimulation of the right and left sensorimotor cortex and sciatic nerve, respectively.…”

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

“…The gold standard model that recapitulates all of the disease aspects observed in ALS would have to be a whole spinal cord organoid obtained from ALS patient-derived iPSCs [ 215 ]. Although this has not yet been developed, recent advances allowed the development of 3-D-engineered spinal cord models [ 216 , 217 ]. In particular, Bowser and Moore developed a combined microphysiological system, where spinal cord spheroids are fabricated using magnetic nanoparticles and then positioned in a 3-D hydrogel construct using magnetic bioprinting [ 217 ].…”

Multi-Functionalized Self-Assembling Peptides as Reproducible 3D Cell Culture Systems Enabling Differentiation and Survival of Various Human Neural Stem Cell Lines

“…Additionally, Collagen has been used as "patches" for in vivo transplantation approaches for the regeneration of injured and/or non-functional tissues. Indeed, in vitro 3D hydrogel cultures provide new tools to direct stem cell differentiation into defined phenotypes prior transplantation (Lai et al, 2018).…”