Abstract 151: Cell-based Therapies for Heart Failure: Changes in Cytokine Expression From Mesenchymal Stem Cells and Induced Pluripotent Stem Cell Derived Cardiomyocytes
Mesenchymal stem cells (MSCs) use paracrine signaling to modulate the cellular microenvironment via expression of cytokines, chemokines, and adhesion molecules to aid and promote endogenous repair. Induced pluripotent stem cell derived cardiomyocyte (iPSC-CMs) and mesenchymal stem cells (MSCs) together may play a synergistic role in changing the microenvironment milieu to allow for endogenous cellular repair through paracrine signaling. Cytokine expression is involved in the progression of heart failure (HF). Using a rat model of HF, cell based therapies with a fibroblast embedded patch only, iPSC-CM patch, and MSCs via tail vein (IV) or intracardiac injections (IC) to the left ventricle (LV) were administered, and RNA was subsequently isolated, and real-time polymerase chain reaction (PCR) was performed for analysis of gene expression.
Evaluation of gene expression revealed significant increases in the expression of connexin 43 with iPSC-CMs (p<0.05). Expression of MMP9 was decreased with MSCs alone (p<0.05) but with the use of the patch with both cell types, its levels were significantly increased (p<0.05). Myosin heavy chain was seen to increase significantly with increasing cell numbers in iPSC-CM therapy (p<0.05). Markers of angiogenesis including vascular endothelial growth factor, angiopoietin, and insulin like growth factor were significantly increased with iPSC-CM patch therapy (p<0.05). Up-regulation of angiogenic cytokines and cardio-protective cytokines may help in slowing progression of HF. Interestingly, we also observed an increase in some markers, which were associated with HF. In conclusion, both iPSC-CM patch and MSCs altered signaling in the setting of HF, perhaps leading to improvement of at the cellular level. An iPSC-CM-based patch and MSCs as an adjuvant therapy may be able to play a role in the setting of HF as cellular therapeutic approach.
Author Disclosures: A.C. Pandey: None. J. Lancaster: None. D. Harris: None. S. Goldman: None. E. Juneman: None.
- © 2015 by American Heart Association, Inc.