Abstract 15487: Building New Cellular Therapy for Heart Failure; Combined Strategy Using Adjuvant Drug and Somatic Stem Cells for Enhancement in Cytokine Paracrine Effects
Background: The efficacy of cell transplantation has been reported to be modest for heart failure and adjuvant drug combined with cell therapy may be one of options to improve the effectiveness in cell therapy. Adipose tissue-derived regenerative cells (ADRCs) have been shown to be an effective cell-source for cardiac cell-transplantation therapy by paracrine effects of adiponectin (APN) which have a possibility in the enhanced cytokine paracrine effects by administration of peroxisome proliferator-activated receptor (PPAR)γ. We hypothesized that additional administration of PPARγ agonist may enhanced APN paracrine effects ADRCs graft, leading further functional recovery in the rat chronic myocardial infarction (MI) model.
Methods and Results: ADRCs were isolated from adipose tissue of adult Lewis rat by the gradient-centrifugation, and embedded in bio-compatible fibrin-glue to produce ADRC-fibrin-glue sheet(FS). The ADRC-FS released APN (21.7±0.9 ng/5x10^6cells/day) or VEGF (85±21 ng/5x10^6cells/day), which were significantly enhanced with PPARγ agonist (51±3.9 and 113±35 ng/5x10^6cells/day, P<0.05, respectively) as assessed by ELISA, in vitro. Transplantation of ADRC-FS(group A), or ADRC-FS mixed with PGZ(group AP) on the epicardium or sham operation was performed in syngeneic Lewis rats that were subjected to LAD ligation 2 weeks prior to the treatment (n=20 each). At 8 weeks after the transplantation, in group AP ejection fraction was significantly increased compared with the group A and the sham group (group AP vs A vs S=63±7.9, 55±2.6, and 35±2.4%, P<0.05 respectively). Moreover, diameter of myocytes and capillary density were significantly improved in the group A and AP than the sham group. Quantitative RT-PCR results showed that the APN, VEGF, HGF, and neuregulin(NRG)-1 transcription were significantly higher in the group A and AP (n=10 each) than in the group S(n=10) at 1 to 2 week after implantation.
Conclusions: Additional administration of PPARγ-agonist enhanced APN paracrine effects of ADRS-FS and functional recovery, suggesting that new cardiac regenerative strategy combined with stem cells and adjuvant drug. This strategy may have a potential in the enhancement of the efficacy of cell therapy in clinical scenario.
Author Disclosures: D. Mori: None. S. Miyagawa: None. S. Fukushima: None. Y. Sawa: None.
- © 2016 by American Heart Association, Inc.