Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) eliminates many epigenetic modifications that characterize differentiated cells. In this study we tested whether functional differences between COPD and non-COPD fibroblasts could be reduced utilizing this approach. Primary fibroblasts from non-COPD and COPD patients were reprogrammed to iPSCs. Reprogrammed iPSCs were positive for oct3/4, nanog and sox2, formed embryoid bodies (EBs) in vitro, and induced teratomas in NOD/SCID mice. Reprogrammed iPSCs were then differentiated into fibroblasts (non-COPD-i and COPD-i, respectively) and were assessed either functionally by chemotaxis and gel contraction or for gene expression by microarrays and compared to their corresponding primary fibroblasts. Primary COPD fibroblasts contracted 3-dimentional (3-D) collagen gels and migrated toward fibronectin less robustly than non-COPD fibroblasts. In contrast, re-differentiated fibroblasts from iPSCs derived from the non-COPD and COPD fibroblasts were similar in response in both functional assays. Microarray analysis identified 1881 genes that were differentially expressed between primary COPD and non-COPD fibroblasts with 605 genes differing by more than 2-fold. After re-differentiation, 112 genes were differentially expressed between COPD-i and non-COPD-i with only three genes by more than 2-fold. Similar findings were observed with miRNA expression: 56 miRNAs were differentially expressed between non-COPD and COPD primary cells; after redifferentiation, only 3 miRNAs were differentially expressed between non-COPD-i and COPD-i fibroblasts. Interestingly, of the 605 genes that were differentially expressed between COPD and non-COPD fibroblasts, 293 genes were changed toward control after re-differentiation. Conclusions: Functional and epigenetic alterations of COPD fibroblasts can be reprogrammed through formation of iPSCs.