The limited regenerative capacity of the adult human myocardium, following injury, leads to remodeling via the accumulation of non-contractile scar tissue, often initiating congestive heart failure (HF). Since current treatment options fail to repair or replace the damaged myocardium and the prevention of ventricular remodeling is limited, novel therapeutic modalities aimed for improving cardiac function and preventing HF are imperative. iPSCs differentiated into cardiomyocytes, suggest a promising potential cell source. Thus far, dermal fibroblasts obtained by biopsy have been a reliable source of cells for reprogramming, however, their cardiac differentiation still holds some drawbacks.
We therefore hypothesized that organ specific fibroblasts, e.g. cardiac fibroblasts, could be an advantageous source for future cardiomyocytes. Hence, we compared iPSCs derived from human dermal tissue (dermal-iPSCs) versus iPSCs derived from human cardiac tissue (cardiac-iPSCs) using Illumina microarray chip gene expression analysis, evaluating whether the cardiac-iPSCs resemble or differ from those dermal-iPSCs, and whether the cardiac-iPSC retain some characteristics of their parental cells.
Four different cell groups were analyzed: the source dermal or cardiac fibroblasts and the corresponding derived dermal or cardiac iPSCs. Approximately 14,000 out of 47,000 probes analyzed were expressed in all four cell groups; from which 6,367 probes were found to be significantly different.
Pivotal genes related to cardiac development and essential for cardiac mechanical and electrical contraction were found to be altered in the cardiac fibroblasts and in the cardiac-iPSCs. Moreover, preliminary results demonstrate that EB`s derived from cardiac-iPSCs begin to contract sooner and in higher percentage than EBs derived from dermal-iPSCs.
These differences in the fibroblasts as well as in the iPSCs suggest that the origin of the reprogrammed somatic cell is crucial for cell function. Hence, cardiac origin reprogrammed fibroblasts may provide a superior source for cardiomyocyte differentiation and consequently will suggest an alternative for future cardiac regeneration.
