OKANO Teruo    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	A novel cell-sheet technology that achieves durable factor VIII delivery in a mouse model of hemophilia A.
Journal	Formal name：PloS one Abbreviation：PLoS One ISSN code：(1932-6203)1932-6203(Linking)
Domestic / Foregin	Foregin
Volume, Issue, Page	8(12),pp.e83280
Author and coauthor	Tatsumi Kohei†, Sugimoto Mitsuhiko*, Lillicrap David, Shima Midori, Ohashi Kazuo, Okano Teruo, Matsui Hideto*
Publication date	2013/12
Summary	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.
DOI	10.1371/journal.pone.0083280
PMID	24358271