Curcumin Improves Human Umbilical Cord-Derived Mesenchymal Stem Cell Survival via ERK1/2 Signaling and Promotes Motor Outcomes After Spinal Cord Injury.
Wu WanjiangChen XinYaxing ChenWang JieZhang HongyanNi FeiLing ChengminFeng ChengjianYuan JichaoJiangkai LinPublished in: Cellular and molecular neurobiology (2020)
Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is thought to be a promising strategy for treating spinal cord injury (SCI). However, the low survival rate of transplanted hUC-MSCs limits their clinical application in cell replacement therapy. Curcumin can suppress inflammation after SCI; however, it remains unknown whether curcumin can modulate the survival of transplanted hUC-MSCs. In this study, to investigate whether curcumin could strengthen the therapeutic effects of hUC-MSC transplantation on SCI, we induced hUC-MSC apoptosis with TNF-α, transplanted hUC-MSC into SCI rats, and assessed the antiapoptotic effect and mechanism of curcumin. LDH release analysis and flow cytometry demonstrated that TNF-α led to hUC-MSC apoptosis and that curcumin increased the hUC-MSC survival rate in a dose-dependent manner. In addition, we showed that the phosphorylation levels of ERK1/2, JNK, and P38 were upregulated in apoptotic hUC-MSCs, while curcumin increased the phosphorylation of ERK1/2 but did not activate JNK or P38, and these effects were reversed by the p42/44 antagonist U0126. Furthermore, we found that the motor function scores and number of surviving HNA-positive cells were significantly increased after curcumin and hUC-MSC transplantation therapy 8 weeks post-SCI, while U0126 markedly attenuated these effects. These data confirmed that curcumin suppressed hUC-MSC apoptosis through the ERK1/2 signaling pathway and that combined curcumin and hUC-MSC treatment improved motor function in rats after SCI. The current research provides a strong basis for hUC-MSC replacement therapy in conjunction with curcumin in the treatment and management of SCI in humans.
Keyphrases
- spinal cord injury
- mesenchymal stem cells
- umbilical cord
- signaling pathway
- replacement therapy
- cell death
- cell cycle arrest
- oxidative stress
- pi k akt
- cell therapy
- cell proliferation
- endothelial cells
- rheumatoid arthritis
- spinal cord
- flow cytometry
- epithelial mesenchymal transition
- stem cells
- machine learning
- electronic health record
- deep learning
- type diabetes
- high glucose
- single cell
- weight loss
- big data
- insulin resistance
- protein kinase
- stress induced
- diabetic rats