Triptolide Improves Early Survival of Mesenchymal Stem Cells Transplanted into Rat Myocardium

Abstract

Objective: To investigate whether triptolide can prolong the survival of rat mesenchymal stem cells (MSCs) transfected with the mouse hyperpolarization-activated cyclic nucleotide-gated channel 4 (mHCN4) gene in the myocardium. Methods: Grafted cell survival was determined using a sex-mismatched cell transplantation model and analysis of Y chromosome-specific Sry gene expression from hearts harvested at different time points after cell transplantation. ELISA and RT-PCR were used to measure protein and mRNA levels, respectively, of nuclear factor (NF)-κB, IL-1ß, IL-6 and TNF-a. Results: Donor cell numbers decreased over time. Pretreatment with triptolide improved graft survival both 24 (29.3 ± 0.9%) and 72 h (17.5 ± 1.2%) after transplantation of MSCs and resulted in a 2.5-fold increase in the total cell number 72 h after cell transplantation. The mRNA expression and protein content of NF-κB, IL-1ß, IL-6 and TNF-a were significantly reduced in the triptolide-treated group compared with the control groups. In addition, triptolide downregulated Bax but upregulated Bcl-2 in the injected region. Conclusions: Transient treatment with triptolide may significantly improve the early survival of MSCs in vivo. The mechanism underlying this effect involves attenuating the inflammatory response via inhibition of the NF-κB signaling pathway.