Dataset Information

Wnt5a-induced exosomes from bone marrow mesenchymal stem cells regulates immune cells via the NF-KB pathway, influencing neural stem cell proliferation and differentiation to promote spinal cord injury repair.

ABSTRACT: Spinal cord injury (SCI) remains a devastating neurological disorder with limited treatment options. Among emerging therapeutic strategies, the transplantation of mesenchymal stem cell-derived exosomes (MSC-Exos) has shown great promise owing to their functional consistency with donor cells, low immunogenicity, and suitability for various delivery routes. Wnt5a, a non-canonical Wnt ligand, has been reported to promote neuronal differentiation and spinal cord regeneration. However, its mechanistic role when delivered via exosomes (Exos) remains unclear. In the present study, the function and underlying mechanism of Wnt5a in promoting neuronal differentiation and spinal cord repair were investigated using bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) in both in vitro and in vivo models. Our results demonstrated that Wnt5a-enriched BMSC-Exos significantly enhanced the proliferation and neuronal differentiation of neural stem cells, while suppressing astrocyte formation. High-throughput RNA sequencing revealed an association between Wnt5a and the nuclear factor-kB (NF-kB) signaling pathway. Intervention with lipopolysaccharide confirmed that Wnt5a exerts a suppressive effect on this pathway. In vivo, the transplantation of Wnt5a-modified BMSC-Exos facilitated the polarization of microglia toward an anti-inflammatory M2 phenotype, promoted neurogenesis, reduced astrocyte accumulation, improved spinal cord tissue architecture, and led to better motor function recovery. Collectively, these findings indicate that Wnt5a enhances the neuroregenerative potential of BMSC-Exos by modulating immune responses and suppressing neuroinflammation, likely through inhibiting the NF-kB signaling pathway. This strategy may offer a promising avenue for treating SCI

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE296458 | GEO | 2025/05/11

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Following spinal cord injury (SCI), the inflammatory storm initiated by microglia/macrophages poses a significant impediment to the recovery process. Exosomes play a crucial role in the transport of miRNAs, facilitating essential cellular communication through the transfer of genetic material. However, the miRNAs from iPSC-NSCs-Exos and their potential mechanisms leading to repair after SCI remain unclear. This study aims to explore the role of iPSC-NSCs-Exos in microglia/macrophage pyroptosis and reveal their potential mechanisms. Methods: iPSC-NSCs-Exos were characterized and identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. A mouse SCI model and a series of in vivo and in vitro experiments were conducted to investigate the therapeutic effects of iPSC-NSCs-Exos. Subsequently, miRNA microarray analysis and rescue experiments were performed to confirm the role of miRNAs in iPSC-NSCs-Exos in SCI. Mechanistic studies were carried out using Western blot, luciferase activity assays, and RNA-ChIP. Results: Our findings revealed that iPSC-NSCs-derived exosomes inhibited microglia/macrophage pyroptosis at 7 days post-SCI, maintaining myelin integrity and promoting axonal growth, ultimately improving mice motor function. The miRNA microarray showed let-7b-5p to be highly enriched in iPSC-NSCs-Exos, and LRIG3 was identified as the target gene of let-7b-5p. Through a series of rescue experiments, we uncovered the connection between iPSC-NSCs and microglia/macrophages, revealing a novel target for treating SCI. Conclusion: In conclusion, we discovered that iPSC-NSCs-derived exosomes can package and deliver let-7b-5p, regulating the expression of LRIG3 to ameliorate microglia/macrophage pyroptosis and enhance motor function in mice after SCI. This highlights the potential of combined therapy with iPSC-NSCs-Exos and let-7b-5p in promoting functional recovery and limiting inflammation following SCI.

Dataset Information

Wnt5a-induced exosomes from bone marrow mesenchymal stem cells regulates immune cells via the NF-KB pathway, influencing neural stem cell proliferation and differentiation to promote spinal cord injury repair.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets