1 research outputs found
BM-MSC-Loaded Graphene-Collagen Cryogels Ameliorate Neuroinflammation in a Rat Spinal Cord Injury Model
A major obstacle to axonal regeneration following spinal
cord injury
(SCI) is neuroinflammation mediated by astrocytes and microglial cells.
We previously demonstrated that graphene-based collagen hydrogels
alone can decrease neuroinflammation in SCI. Their regenerative potential,
however, is poorly understood and incomplete. Furthermore, stem cells
have demonstrated both neuroprotective and regenerative properties
in spinal cord regeneration, although there are constraints connected
with the application of stem cell-based therapy. In this study, we
have analyzed the regeneration capability of human bone marrow mesenchymal
stem cell (BM-MSC)-loaded graphene-cross-linked collagen cryogels
(Gr-Col) in a thoracic (T10-T11) hemisection model of SCI. Our study
found that BM-MSC-loaded Gr-Col improves axonal regeneration, reduces
neuroinflammation by decreasing astrocyte reactivity, and promotes
M2 macrophage polarization. BM-MSC-loaded-Gr-Col demonstrated enhanced
regenerative potential compared to Gr-Col and the injury group control.
Next-generation sequencing (NGS) analysis revealed that BM-MSC-loaded-Gr-Col
modulates the JAK2-STAT3 pathway, thus decreasing the reactive and
scar-forming astrocyte phenotype. The decrease in neuroinflammation
in the BM-MSC-loaded-Gr-Col group is attributed to the modulation
of Notch/Rock and STAT5a/b and STAT6 signaling. Overall, Gene Set
Enrichment Analysis suggests the promising role of BM-MSC-loaded-Gr-Col
in promoting axonal regeneration after SCI by modulating molecular
pathways such as the PI3/Akt pathway, focal adhesion kinase, and various
inflammatory pathways