Curcumin Improves Human Umbilical Cord-Derived Mesenchymal Stem Cell Survival via ERK1/2 Signaling and Promotes Motor Ou
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ORIGINAL RESEARCH
Curcumin Improves Human Umbilical Cord‑Derived Mesenchymal Stem Cell Survival via ERK1/2 Signaling and Promotes Motor Outcomes After Spinal Cord Injury Wu Wanjiang1 · Chen Xin1 · Chen Yaxing1 · Wang Jie2 · Zhang Hongyan1 · Ni Fei3 · Ling Chengmin1 · Feng Chengjian4 · Yuan Jichao2 · Lin Jiangkai1 Received: 23 September 2020 / Accepted: 18 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Human umbilical cord-derived mesenchymal stem cells · Curcumin · Spinal cord injury · Antiapoptosis · Dualtarget therapy
Wu Wanjiang and Chen Xin have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10571-020-01018-7) contains supplementary material, which is available to authorized users. * Yuan Jichao [email protected] * Lin Jiangkai [email protected] 1
Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Army Medical University), Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China
Abbreviations BBB Basso, Beattie, and Bresnahan BMSCs Bone marrow-derived MSCs CCK-8 Cell counting kit-8 Cur Curcumin DMSO Dimethylsulfoxide ERK Extracellular-regulated protein ki
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