1. Curcumin Improves Human Umbilical Cord-Derived Mesenchymal Stem Cell Survival via ERK1/2 Signaling and Promotes Motor Outcomes After Spinal Cord Injury
- Author
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Chen Yaxing, Feng Chengjian, Chen Xin, Ling Chengmin, Lin Jiang-kai, Wu Wanjiang, Yuan Jichao, Zhang Hong-yan, Ni Fei, and Wang Jie
- Subjects
0301 basic medicine ,Curcumin ,MAP Kinase Signaling System ,p38 mitogen-activated protein kinases ,Inflammation ,Pharmacology ,Mesenchymal Stem Cell Transplantation ,Umbilical Cord ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,Animals ,Humans ,Spinal cord injury ,Spinal Cord Injuries ,business.industry ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Cell Biology ,General Medicine ,medicine.disease ,Rats ,Transplantation ,030104 developmental biology ,chemistry ,Apoptosis ,Signal transduction ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
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.
- Published
- 2020