Crosstalk between neural tissue-specific extracellular matrix and mesenchymal stem cells and their promotion of peripheral nerve regeneration in vivo

A favorable regenerative microenvironment is essential for peripheral nerve regeneration. Neural tissue-specific extracellular matrix (ECM) is a natural material that helps direct cell behavior and promote nerve regeneration. Mesenchymal stem cell (MSC) transplantation is effective in promoting peripheral nerve regeneration. In conclusion, this study summarizes the in vivo response characteristics and underlying molecular mechanisms of BMSCs and ADSCs on neural-tissue-derived ECM materials, providing new clues when selecting the optimal MSCs for repairing PNI in the clinic. Overall design: Here, a rat sciatic nerve deficit injury model was used to investigate in vivo response characteristics, molecular mechanisms, and effects of adipose-derived mesenchymal stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) on neural tissue-derived ECM materials to promote peripheral nerve repair. The results showed that BMSCs exhibited more significant immunomodulatory effects on tissue-derived ECMs, as evidenced by the up-regulation of interleukin (IL)-10, down-regulation of IL-1ß and tumor necrosis factor-alpha (TNF-a) expression, promotion of M1-type macrophage polarization to M2-type, and a significant increase in the number of regulatory T cells (Tregs). However, ADSCs exhibited more pronounced features of pro-myelination and vasculogenesis on tissue-derived ECM materials. To further elucidate the underlying molecular mechanisms, changes in long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were systematically investigated using whole transcriptome sequencing. Notably, both BMSCs and ADSCs were effective in repairing peripheral nerve injury (PNI) in the presence of neural tissue-derived ECM. Total: 9 samples.