Training Neural Stem Cells on Functional Collagen Scaffolds for Severe Spinal Cord Injury Repair

Abstract

Neural stem cells (NSCs) transplantation is regarded as a promising therapeutic strategy to treat severe spinal cord injury (SCI) by compensating the neuronal loss. However, significant challenges including long‐term survival, directed neuronal differentiation, and functional integration of the transplanted NSCs and their progenies within the host spinal cord are yet to be solved. In this study, NSCs are trained on differently modified collagen scaffolds to increase their neuronal differentiation rate when cultured under the simulated SCI microenvironment. Then, a functional scaffold is screened out, on which the cultured NSCs show high neuronal differentiation rate and generate both sensory and motor mature neurons. Subsequently, that NSC seeded functional scaffold is transplanted into a rat severe SCI model. The results show that higher endogenous neurogenesis efficiency as well as in vivo survival and neuronal differentiation rate of the grafted NSCs are observed. Moreover, both sensory and motor neurons are found to be differentiated from the grafted NSCs in the lesion site and those newly generated neurons can functionally interact with each other and the host neurons. Taken together, the in vitro training systems for modulating the differentiation profiles of NSCs are instructive and exhibit strong potentials for SCI treatments.

3D Printed Stem‐Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds

“…Advances in creating new therapies for the CNS have shown promise through the combination of neural stem cell transplantation and biomaterial manufacturing . For instance, injection of neural stem/progenitor cells into a subacute spinal cord contusion in rodent models has resulted in improved locomotor functional recovery .…”

“…However, one problem has been that direct injection of cells into a lesion cavity has the disadvantage of both lack of structure and a support system . To bridge this gap, implantation of biocompatible scaffolds (including 3D printed scaffolds) and/or their combination with neural stem/progenitor cells and growth factors has been pursued to provide cell transplant, biological cues, and physical guides, opening opportunities to test new therapeutic options . Yet, few of these studies have been extended to chronic injury, which is an unmet public health need.…”

Radially Aligned Electrospun Fibers with Continuous Gradient of SDF1α for the Guidance of Neural Stem Cells

“…It was found that the NT-3 group had a substantial amount of endogenous nestin positive NSCs in the lesion area, and more cells were found in the rostral and caudal regions at the early time points of 20 d, indicating the directional migration of endogenous NSCs from the rostral and caudal ends. [ 7 ] In our recent research, [ 8 ] NSC-seeded functional collagen scaffolds were transplanted into a rat T8 complete removal model. It was found that more amount of endogenous nestin positive NSCs were observed, and the grafted and endogenous NSCs exhibited enhanced neuronal differentiation.…”

EMSCs Build an All‐in‐One Niche via Cell–Cell Lipid Raft Assembly for Promoted Neuronal but Suppressed Astroglial Differentiation of Neural Stem Cells

“…Although the intrinsic activation of neural stem cells (NSCs) attempts to participate in neural repair shortly after SCI, the nonpermissive niche at the injury site severely hampers the nerve regeneration process. Moreover, the inhospitable niche at the lesion site often results in astroglial but not neuronal differentiation or even failed survival of the allogeneic NSCs . Therefore, overcoming the inhibitory microenvironment and reconstruction of a permissive niche at the injury site would represent a fundamental advance in SCI treatment.…”