Back to Search Start Over

Progress and challenges in the development of a cell-based therapy for hemophilia A.

Authors :
Fomin ME
Togarrati PP
Muench MO
Source :
Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2014 Dec; Vol. 12 (12), pp. 1954-65. Date of Electronic Publication: 2014 Oct 31.
Publication Year :
2014

Abstract

Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review, we discuss the possibilities, progress, and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific induced pluripotent stem cells.<br /> (© 2014 International Society on Thrombosis and Haemostasis.)

Details

Language :
English
ISSN :
1538-7836
Volume :
12
Issue :
12
Database :
MEDLINE
Journal :
Journal of thrombosis and haemostasis : JTH
Publication Type :
Academic Journal
Accession number :
25297648
Full Text :
https://doi.org/10.1111/jth.12750