The
repair of spinal cord injury (SCI) is still a tough clinical
challenge and needs innovative therapies. Mitochondrial function is
significantly compromised after SCI and has emerged as an important
factor causing neuronal apoptosis and hindering functional recovery.
In this study, umbilical cord mesenchymal stem cells (UCMSC), which
are promising seed cells for nerve regeneration, and basic fibroblast
growth factor (bFGF) that have been demonstrated to have a variety
of effects on neural regeneration were jointly immobilized in extracellular
matrix (ECM) and heparin-poloxamer (HP) to create a polymer bioactive
system that brings more hope and possibility for the treatment of
SCI. Our results in vitro and in vivo showed that the UCMSC-bFGF-ECM-HP thermosensitive hydrogel has good
therapeutic effects, mainly in reducing apoptosis and improving the
mitochondrial function. It showed promising utility for the functional
recovery of impaired mitochondrial function by promoting mitochondrial
fusion, reducing pathological mitochondrial fragmentation, increasing
mitochondrial energy supply, and improving the metabolism of MDA,
LDH, and ROS. In addition, we uncovered a distinct molecular mechanism
underlying the protective effects associated with activating p21-activated
kinase 1 (PAK1) and mitochondrial sirtuin 4 (SIRT4) by the UCMSC-bFGF-ECM-HP
hydrogel. The expansion of new insights into the molecular relationships
between PAK1 and SIRT4, which links the mitochondrial function in
SCI, can lay the foundation for future applications and help to provide
promising interventions of stem-cell-based biological scaffold therapies
and potential therapeutic targets for the clinical formulation of
SCI treatment strategies.
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