| First Author | Tatsumi K | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e83280 |
| PubMed ID | 24358271 | Mgi Jnum | J:209857 |
| Mgi Id | MGI:5568828 | Doi | 10.1371/journal.pone.0083280 |
| Citation | Tatsumi K, et al. (2013) A novel cell-sheet technology that achieves durable factor VIII delivery in a mouse model of hemophilia A. PLoS One 8(12):e83280 |
| abstractText | Gene- or cell-based therapies aimed at creating delivery systems for coagulation factor VIII (FVIII) protein have emerged as promising options for hemophilia A treatment. However, several issues remain to be addressed regarding the efficacies and adverse events of these new classes of therapies. To improve an existing cell-based therapy involving the subcutaneous transplantation of FVIII-transduced blood outgrowth endothelial cells (BOECs), we employed a novel cell-sheet technology that allows individual dispersed cells to form a thin and contiguous monolayer without traditional bioabsorbable scaffold matrices. Compared to the traditional methodology, our cell-sheet approach resulted in longer-term and 3-5-fold higher expression of FVIII (up to 11% of normal) in recipient hemophilia A mice that lacked a FVIII humoral immune response due to transient immunosuppression with cyclophosphamide. Histological studies revealed that the transplanted BOEC sheets were structured as flat clusters, supporting the long-term expression of therapeutic FVIII in plasma from an ectopic subcutaneous space. Our novel tissue-engineering approach using genetically modified BOEC sheets could aid in development of cell-based therapy that will allow safe and effective in vivo delivery of functional FVIII protein in patients with hemophilia A. |
