The role of secretome from mesenchymal stromal cells in promoting nerve regeneration after neurotmesis
摘要
Neurotmesis, remains a significant clinical challenge due to limited intrinsic regenerative capacity and suboptimal outcomes of current therapies. Mesenchymal stromal cells (MSCs) secretome has emerged as a promising cell-free alternative, providing neurotrophic and immunomodulatory factors to support nerve repair. This study aimed to evaluate the regenerative efficacy of primed adipose-derived MSC secretome in a rat model of sciatic nerve neurotmesis.
MethodsHuman and rat adipose-derived MSCs were cultured and primed under hypoxic and inflammatory conditions. Secretomes were characterized by nanoparticle tracking analysis, proteomics, and total protein quantification. Neurotmesis was induced in Wistar rats, followed by repair with biomaterial alone or combined with human or rat secretome. Functional recovery was assessed by neurophysiological measurements at 6 months. Molecular and morphological regeneration was evaluated.
ResultsSecretome priming enhanced the secretion of neurotrophic factors and immunomodulatory proteins, as confirmed by transcriptomic and proteomic analyses. In vivo, secretome-treated groups showed significantly improved neurophysiological recovery and increased NGF levels. qPCR revealed upregulation of myelination-associated genes in treated nerves. Histological and TEM analyses demonstrated robust axonal regeneration.
ConclusionsPrimed MSC secretome markedly enhances structural and functional recovery after sciatic nerve neurotmesis, supporting its potential as a safe, effective, and scalable cell-free therapy for peripheral nerve repair.
Graphical Abstract