Bone marrow-derived neural crest precursors improve nerve defect repair partially through secreted trophic factors

Abstract

BackgroundEmerging evidence suggests that neural crest-derived cells (NCCs) present important functions in peripheral nerve regeneration to correct the insufficiency of autogenous Schwann cells. Postmigratory NCCs have been successfully isolated from adult rat bone marrow in our previous work. In this study, we aim to provide neural crest-derived Schwann cell precursors (SCPs) for repair of nerve defects in adult rats, and partially reveal the mechanisms involved in neuroregeneration of cell therapy.MethodsA clonal cell line of neural crest precursors of rat bone marrow origin (rBM-NCPs) with SCP identity was expanded in adherent monolayer culture to ensure the stable cell viability of NCPs and potentiate the repair of nerve defects after rBM-NCPs implantation based on tissue engineering nerve grafts (TENG). Here the behavioral, morphological, and electrophysiological detection was performed to evaluate the therapy efficacy. We further investigated the treatment with NCP-conditioned medium (NCP-CM) to sensory neurons after exposure to oxygen-glucose-deprivation (OGD) and partially compared the expression of trophic factor genes in rBM-NCPs with that in mesenchymal stem cells of bone marrow origin (rBM-MSCs).ResultsIt was showed that the constructed TENG with rBM-NCPs loaded into silk fibroin fiber scaffolds/chitosan conduits repaired 10-mm long sciatic nerve defects more efficiently than conduits alone. The axonal regrowth, remyelination promoted the reinnervation of the denervated hind limb muscle and skin and thereby alleviated muscle atrophy and facilitated the rehabilitation of motor and sensory function. Moreover, it was demonstrated that treatment with NCP-CM could restore the cultured primary sensory neurons after OGD through trophic factors including epidermal growth factor (EGF), platelet-derived growth factor alpha (PDGFα), ciliary neurotrophic factor (CNTF), and vascular endothelial growth factor alpha (VEGFα).ConclusionsIn summary, our findings indicated that monolayer-cultured rBM-NCPs cell-based therapy might effectively repair peripheral nerve defects partially through secreted trophic factors, which represented the secretome of rBM-NCPs differing from that of rBM-MSCs.

Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells

“…OGD of sensory neurons was performed as previously described [ 9 ]. Briefly, sensory neurons were cultured in glucose-free neurobasal medium (Gibco) in 37 °C incubator with 5% CO 2 and 1% oxygen concentration for 8 h, and switched back to their original culture condition with treatment of low-, medium-, and high-dose EVs for 24 h; additionally, in sequent experiments, high-dose EVs were applied and PI3K inhibitor LY294002 (CST) was added to medium.…”

“…Notably, neural crest stem/precursor cells from postnatal bone marrow, dental pulp, and skin show desirable potential to generate Schwann-like cell [ 7 ]. The Schwann-like cells can respond to tissue injury, similar to endogenous SCs, modulating neuronal activity and regulating tissue microenvironment homeostasis [ 8 , 9 ]. During the development process, in vivo neural crest cells give rise to SCs; therefore, focus on Schwann-like cells from reliable neural crest cell source for neuroprotection and neuro-regeneration is a significant work.…”

Additive-lathe 3D bioprinting of bilayered nerve conduits incorporated with supportive cells

“…In the pursuit of an effective nerve conduit many biological strategies, including stem cell therapy [ 12 , 13 ], have been employed during fabrication. Bone marrow mesenchymal stem cells (BMSCs), multipotent cells with the ability to differentiate into many lineages including neural-like lineages, were repeatedly found to support nerve regeneration [ 10 , [14] , [15] , [16] ]. However, cell seeding protocols typically involve either cell attachment in culture after fabrication, which potentially results in cell detachment in vivo , or cell lumen injection, which is susceptible to leakage [ 17 ].…”

Exosomes Derived From Stem Cells From Apical Papilla Promote Craniofacial Soft Tissue Regeneration Through Enhancing Cdc42-Mediated Vascularization

“…Meanwhile, the neural crest-derived MSCs carry neurovascular factors such as vascular endothelial growth factor, platelet derived growth factor, and brain-derived neurotrophic factor, which mediate the angiogenic process to improve tissue regeneration and treat ischemic diseases [24][25][26]. Exosomes have similar cellular properties to the parent cell [27].…”