| First Author | Reinecke H | Year | 2013 |
| Journal | Cardiovasc Pathol | Volume | 22 |
| Issue | 1 | Pages | 91-5 |
| PubMed ID | 22512900 | Mgi Jnum | J:345761 |
| Mgi Id | MGI:6840136 | Doi | 10.1016/j.carpath.2012.03.005 |
| Citation | Reinecke H, et al. (2013) Lack of thrombospondin-2 reduces fibrosis and increases vascularity around cardiac cell grafts. Cardiovasc Pathol 22(1):91-5 |
| abstractText | BACKGROUND: Fibrosis around cardiac cell injections represents an obstacle to graft integration in cell-based cardiac repair. Thrombospondin-2 (TSP-2) is a pro-fibrotic, anti-angiogenic matricellular protein and an attractive target for therapeutic knockdown to improve cardiac graft integration and survival. METHODS: We used a TSP-2 knockout (KO) mouse in conjunction with a fetal murine cardiomyocyte grafting model to evaluate the effects of a lack of TSP-2 on fibrosis, vascular density, and graft size in the heart. RESULTS: Two weeks after grafting in the uninjured heart, fibrosis area was reduced 4.5-fold in TSP-2 KO mice, and the thickness of the peri-graft scar capsule was reduced sevenfold compared to wild-type (WT). Endothelial cell density in the peri-graft region increased 2.5-fold in the absence of TSP-2, and cardiomyocyte graft size increased by 46% in TSP-2 KO hearts. CONCLUSIONS: TSP-2 is a key regulator of fibrosis and angiogenesis following cell grafting in the heart, and its absence promotes better graft integration, vascularization, and survival. SUMMARY: Fibrosis around cardiac cell injections impairs graft integration in cell-based cardiac repair. TSP-2 is a pro-fibrotic, anti-angiogenic matricellular protein. Using a TSP-2-knockout mouse model and cardiac cell transplantation, we found significantly reduced fibrosis and increased endothelial cell density in the peri-graft region. Thus, TSP-2 is an attractive target for therapeutic knockdown to improve cardiac graft integration and survival. |
