Various immune cells and cytokines are present in the aftermath of peripheral nerve injuries (PNI), and coordination of the local inflammatory response is of great significance for the recovery of PNI. Mesenchymal stem cells (MSCs) exhibit immunosuppressive and anti-inflammatory abilities which can accelerate tissue regeneration and attenuate inflammation, but the role of MSCs in the regulation of the local inflammatory microenvironment after PNI has not been widely studied. Here, we summarize the known interactions between MSCs, immune cells, and inflammatory cytokines following PNI with a focus on the immunosuppressive role of MSCs. We also discuss the immunomodulatory potential of MSC-derived extracellular vesicles as a new cell-free treatment for PNI.
Following peripheral nerve injury (PNI), Wallerian degeneration (WD) in the distal stump can generate a microenvironment favorable for nerve regeneration. Brief low‐frequency electrical stimulation (ES) is an effective treatment for PNI, but the mechanism underlying its effect on WD remains unclear. Therefore, we hypothesized that ES could enhance nerve regeneration by accelerating WD. To verify this hypothesis, we used a rat model of sciatic nerve transection and provided ES at the distal stump of the injured nerve. The injured nerve was then evaluated after 1, 4, 7, 14 and 21 days post injury (dpi). The results showed that ES significantly promoted the degeneration and clearance of axons and myelin, and the dedifferentiation of Schwann cells. It upregulated the expression of BDNF and NGF and increased the number of monocytes and macrophages. Through transcriptome sequencing, we systematically investigated the effect of ES on the molecular processes involved in WD at 4 dpi. Evaluation of nerves bridged using silicone tubing after transection showed that ES accelerated early axonal and vascular regeneration while delaying gastrocnemius atrophy. These results demonstrate that ES promotes nerve regeneration by accelerating WD and upregulating the expression of neurotrophic factors.
Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD. The results of the present study suggest that pretreatment with curcumin can prevent the development of LIDD in rats. It was revealed that treatment with curcumin significantly reduced interleukin (IL)‑1β and IL‑6, iNOS, COX‑2 and MMP‑9 levels in rats with LIDD. In addition, treatment with curcumin reduced the mRNA expression levels of TGF‑β1 and TGF‑β2, whereas it increased the mRNA expression levels of BDNF in rats with LIDD. In conclusion, the present findings indicate that curcumin may exert protective effects on LIDD development, exerting its action through the regulation of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF.
Mesenchymal stem cells (MSCs) have been shown to be able to inhibit cancer cells growth. In this study, we investigate the role and the molecular mechanism of hypoxia-inducible factor 1-alpha (HIF-1α) in inhibition of cancer cell proliferation by human MSCs through depletion and overexpression of HIF-1α in human MSCs. We found that the cell culture medium from HIF-1α-depleted Z3 cells significantly promotes breast cancer MCF-7 cell proliferation and colony formation. The expression of p21 is increased in MCF-7 cells, but p53 level remains unchanged. In contrast, the cultured medium from HIF-1α-overexpressed Z3 cells dramatically inhibits MCF-7 cell proliferation and colony formation. The expression of p21 is inhibited in MCF-7 cells, but p53 does not change. We conclude HIF-1α promotes inhibitory effect of human MCSs on breast cancer cell proliferation and colony formation. This process is tightly correlated with cell cycle protein p21 level in cancer cells.
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