| First Author | Prisco AR | Year | 2016 |
| Journal | Stem Cells | Volume | 34 |
| Issue | 7 | Pages | 1922-33 |
| PubMed ID | 26867147 | Mgi Jnum | J:238119 |
| Mgi Id | MGI:5818124 | Doi | 10.1002/stem.2339 |
| Citation | Prisco AR, et al. (2016) Tumor Necrosis Factor alpha Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB. Stem Cells 34(7):1922-33 |
| abstractText | Shortly after the discovery of endothelial progenitor cells (EPCs) in 1997, many clinical trials were conducted using EPCs as a cellular based therapy with the goal of restoring damaged organ function by inducing growth of new blood vessels (angiogenesis). Results were disappointing, largely because the cellular and molecular mechanisms of EPC-induced angiogenesis were not clearly understood. Following injection, EPCs must migrate to the target tissue and engraft prior to induction of angiogenesis. In this study EPC migration was investigated in response to tumor necrosis factor alpha (TNFalpha), a pro-inflammatory cytokine, to test the hypothesis that organ damage observed in ischemic diseases induces an inflammatory signal that is important for EPC homing. In this study, EPC migration and incorporation were modeled in vitro using a coculture assay where TNFalpha treated EPCs were tracked while migrating toward vessel-like structures. It was found that TNFalpha treatment of EPCs increased migration and incorporation into vessel-like structures. Using a combination of genomic and proteomic approaches, NF-kB mediated upregulation of CADM1 was identified as a mechanism of TNFalpha induced migration. Inhibition of NF-kB or CADM1 significantly decreased migration of EPCs in vitro suggesting a role for TNFalpha signaling in EPC homing during tissue repair. Stem Cells 2016;34:1922-1933. |
