Metal-organic framework materials promote neural differentiation of dental pulp stem cells in spinal cord injury

Abstract

Spinal cord injury (SCI) is accompanied by loss of Zn2+, which is an important cause of glutamate excitotoxicity and death of local neurons as well as transplanted stem cells. Dental pulp stem cells (DPSCs) have the potential for neural differentiation and play an immunomodulatory role in the microenvironment, making them an ideal cell source for the repair of central nerve injury, including SCI. The zeolitic imidazolate framework 8 (ZIF-8) is usually used as a drug and gene delivery carrier, which can release Zn2+ sustainedly in acidic environment. However, the roles of ZIF-8 on neural differentiation of DPSCs and the effect of combined treatment on SCI have not been explored. ZIF-8-introduced DPSCs were loaded into gelatin methacryloyl (GelMA) hydrogel and in situ injected into the injured site of SCI rats. Under the effect of ZIF-8, axon number and axon length of DPSCs-differentiated neuro-like cells were significantly increased. In addition, ZIF-8 protected transplanted DPSCs from apoptosis in the damaged microenvironment. ZIF-8 promotes neural differentiation and angiogenesis of DPSCs by activating the Mitogen-activated protein kinase (MAPK) signaling pathway, which is a promising transport nanomaterial for nerve repair.

Metal–organic framework-based platforms for implantation applications: recent advances and challenges

“…68 Zhou et al used ZIF-8 to support dental pulp stem cells and then loaded them into gelatin methylacrylyl hydrogels and injected them into the injured spinal cord of rats to achieve effective nerve repair. 69…”

The potential therapeutic roles of dental pulp stem cells in spinal cord injury

“…Differentiated DPSCs not only display motor neuron-like morphology, with Nissl bodies in the cytoplasm, but also express several motor neuron specific genes in post-induction stage, such as Olig2, Islet-1 and HB9. In animal models of SCI, transplantation of dental-derived mesenchymal stem cell alone or as part of designed engineered tissue also have been shown to differentiate neuron-like phenotype, replacing the defective neuronal tissue and improving functional recovery after SCI ( Zhang et al, 2016 ; Yang et al, 2017 ; Kabatas et al, 2018 ; Qian et al, 2023 ; Zhou et al, 2023 ). Recently, Qian et al found the DPSC-loaded microspheres have improved stemness and higher neurogenic differentiation potential of DPSCs, promoting neural tissue regeneration in rat models of SCI ( Qian et al, 2023 ).…”

“…Moreover, usage of the DPSC-chitosan grafts improve locomotor function in animal models of SCI, by the secretion of BDNF, GDNF and NT-3, reducing the accumulation of active-caspase 3, and impairing axonal loss and degradation. Zhou et al reported the roles of bioactive material zeolitic imidazolate framework 8 (ZIF-8) on neural differentiation of DPSCs ( Zhou et al, 2023 ). These authors found after injection of methacryloyl hydrogel containing ZIF-8-introduced DPSCs into the lesion, axon number and axon length of DPSCs-differentiated neuron-like cells were significantly increased.…”

BM-MSC-Loaded Graphene-Collagen Cryogels Ameliorate Neuroinflammation in a Rat Spinal Cord Injury Model

“…3 There is clear evidence of improved axonal regeneration, remyelination, decrease in astrogliosis, modulation of macrophages/microglial polarization, and promotion of axonal conduction following BM-MSC transplantation into the rat spinal cord following contusive injuries. 4,5 A single injection of BM-MSCs is sufficient to exert its regenerative effect. However, a number of clinical studies administered cells multiple times to exert its positive effect.…”

“…Among these, BM-MSCs have been seen as the source with the most potential for SCI treatment . There is clear evidence of improved axonal regeneration, remyelination, decrease in astrogliosis, modulation of macrophages/microglial polarization, and promotion of axonal conduction following BM-MSC transplantation into the rat spinal cord following contusive injuries. , A single injection of BM-MSCs is sufficient to exert its regenerative effect. However, a number of clinical studies administered cells multiple times to exert its positive effect. , It is hypothesized that the transplanted cells can only survive for a limited period in a hostile environment in the SCI microenvironment.…”