Abstract
Background
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation are assumed as a promising strategy in spinal cord injury (SCI). However, the complex pathological microenvironment after SCI induces the apoptosis of hUC-MSCs, which limits the clinical application for the cell replacement therapy.
Methods
In this study, in order to investigate whether combined with curcumin could strengthen the therapeutic effects of hUC-MSCs transplantation for SCI, we mediated the apoptosis of hUC-MSCs with TNF-α and transplanted hUC-MSCs into SCI rats, followed by assessed the anti- apoptosis effect and mechanism of curcumin.
Results
LDH release test and flow cytometry demonstrated that TNF-α led to the hUC-MSCs apoptosis and curcumin increased survival rate of hUC-MSCs with dose-dependent. In addition, we showed that the phosphorylation levels of ERK, JNK and P38 were up-regulated in the hUC-MSCs apoptosis, while curcumin strengthened the phosphorylation of ERK, but not activated the JNK and P38, which was reversed by p42/44 antagonist U0126. Furthermore, we exhibited that the motor function scores and surviving HNA-positive cells were significantly increased after curcumin combined with hUC-MSCs transplantation therapy 8 weeks post SCI, while U0126 markedly attenuated these phenomenons.
Conclusions
The aforementioned data confirmed that curcumin suppressed the apoptosis of hUC-MSCs through ERK signal pathway and combined curcumin with hUC-MSCs treatment improved motor function after SCI in rats. The current research provides a strong basis for hUC-MSCs replacement therapy in conjunction with curcumin in the treatment and management of SCI in human.
Differentiation of human adipose-derived stem cells into neuron/motoneuron-like cells for cell replacement therapy of spinal cord injury
