Table 1.
Summary of endogenous neurogenesis strategies and their effectiveness for spinal cord injury repair
| Publication | Species | Treatment | Autonomous locomotor recovery | Electrophysiological improvement | Proposed mechanism | Synapselike structure in the injured site | Pathway | |
|---|---|---|---|---|---|---|---|---|
| Transplanting biomaterials mimicking the mechanical property of spinal cord | ||||||||
| Li et al. [45] 2020 | Rat | Injectable nanofiber-hydrogel composite | Yes | NR | Supporting proregenerative macrophage polarization, angiogenesis, axon growth, and neurogenesis in the injured tissue | NR | NR | |
| Zhao et al. [48] 2021 | Rat | Gelatin and hyaluronic acid-based hydrogels made of principle components of extracellular matrix | Yes | NR | Improving endogenous NSC migration and neurogenesis, neuron maturation and axonal regeneration. | NR | NR | |
| Zhu et al. [49] 2021 | Mouse | Mg/Al layered double hydroxide nanoparticles | Yes | Yes | Accelerating NSCs migration, neural differentiation, Ca(2+) channel activation, and inducible action potential generation | NR | Inhibiting inflammation through transforming growth factor-β receptor 2 | |
| Zhou et al. [51] 2018 | Biocompatible conducting polymer hydrogel | Yes | NR | Activating endogenous NSC neurogenesis in the lesion in vivo | NR | NR | ||
| Luo et al. [52] 2022 | Rat | Injectable, self-healing and electroconductive hydrogels | Yes | NR | Activating endogenous NSC neurogenesis, and inducing myelinated axon regeneration into the lesion | NR | Activation of the Pl3k/Akt and MEK/ERK pathways | |
| Ma et al. [53] 2021 | Rat | Poly (lactic-co-glycolic acid) shellensheathed decellularized spinal cord scaffolds | Yes | NR | Creating a favorable microenvironment for migration, residence, and neuronal differentiation of endogenous NSCs and presenting mild immunogenic property, polarizing macrophages to the M2 phenotype | NR | NR | |
| Growth factor-loaded biomaterials | ||||||||
| Yang et al. [40] 2015 | Rat | NT-3-coupled chitosan biomaterial | Yes | NR | Attracted NSCs to migration, differentiation, and formation of functional neural networks | Yes | NR | |
| Li et al. [64] 2016 | Rat and canine | NT-3/fibroin coated gelatin sponge scaffold | Yes | NR | Improved tissue regeneration, reduced cavity areas and abrogated the inflammatory response | NR | Eliciting inflammatory response by reducing TNF-α and CD68 positive cells | |
| Xie et al. [66] 2018 | Rat | Sodium hyaluronate-CNTF scaffold | Yes | Yes | Facilitate NSCs migration, differentiation, forming synaptic contact, and receiving glutamatergic excitatory synaptic input | Yes | NR | |
| Shang et al. [67] 2019 | Rat | bFGF controlled release system | Yes | NR | Reduce microglial activation, promote revascularization, elicit endogenous neurogenesis and promote regrowth of transected axons | Yes | NR | |
| Biomaterials releasing drugs | ||||||||
| Li et al. [71] 2017 | Rat and canine | Cetuximab in modified linear ordered collagen scaffolds | Yes | NR | Neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation | Yes | NR | |
| Fan et al. [36] 2017 | Rat | EGFR antibody with a collagenbinding domain | Yes | NR | Promoted neuronal differentiation and neurite outgrowth under myelin | NR | NR | |
| Yin et al. [72] 2018 | Canine | Taxol-modified collagen scaffold | Yes | Yes | Increased neurogenesis, axon regeneration and reduce glial scar formation | NR | NR | |
| Yang et al. [73] 2021 | Rat | LDN193189, SB431542, CHIR99021 and P7C3-A20 in an injectable collagen hydrogel | Yes | NR | Induced neurogenesis, increase neuronal differentiation of spinal cord NSCs and inhibited astrogliogenesis | NR | NR | |
| Biomaterials with exogenous stem cells | ||||||||
| Yuan et al. [80] 2021 | Rat | DNA hydrogel-carrying exogenous NSCs | Yes | Yes | Enabling sufficient migration, proliferation, and differentiation of both implanted and endogenous NSCs | NR | NR | |
| Li et al. [71] 2017 | Canine | Collagen-based biomaterial loading with human umbilical cordderived mesenchymal stem cells | Yes | NR | Fascinated newborn neurons matured into 5-HT positive neurons and the regenerated axon with remyelination and synapse connection | Yes | NR | |
| Wang et al. [60] 2021 | Rat | Modified scaffolds loading NSCs overexpressing NGF | Yes | NR | Modulating the microenvironment and enhancing endogenous neurogenesis | NR | Activating TrkA, upregulating CREB and microRNA-132 around the lesion focus. | |
| Physiotherapy | ||||||||
| Xu et al. [85] 2021 | Rat | Electroacupuncture on Governor Vessel acupoints | Yes | NR | Activating the intrinsic growth ability of injured spinal neuron | Yes | GV-EA activating CGRP/ RAMP1/alphaCaMKII pathway | |
| Xu et al. [86] 2019 | Rat | Fire needle | Yes | NR | Promoting endogenous NSCs proliferation differentiating into neurons | NR | Activation of Wnt/β-catenin and inhibiting the overexpression of ERK. | |
| Combinatorial treatments | ||||||||
| Li et al. [65] 2021 | Rat | TrkC-modified NSC-derived neural network tissue in the NF-GS | Yes | NR | Establishing favorable microenvironment and supporting the long-time survival of both exogenous neurons and endogenous newborn neurons | Yes | NR | |
| Liu et al. [43] 2021 | Rat | Combining thermosensitive polymer electroactive hydrogel loaded with NGF with electrical stimulation | Yes | NR | Promoted the neuronal differentiation of NSCs and axonal growth | NR | NR | |
NR, not reported; NSCs, neural stem cells; MEK/ERK, mitogen-activated protein kinase kinase/extracellular signal-regulated kinase; TNF-α; tumor necrosis factor-α; CNTF, ciliary neurotrophic factor; NT-3, neurotrophin-3; bFGF, basic fibroblast growth factor; EGFR, epidermal growth factor receptor; 5-HT, 5-hydroxytryptamine; NGF, nerve growth factors; CREB, cAMP-response element binding protein; GV-EA, electroacupuncture on Governor Vessel acupuncture points; NF-GS, NT-3/fibroin coated gelatin sponge scaffold; TrkC, tropomyosin receptor kinase C.