This invention may enable the re-engineering of mature human endothelium (blood vessels) into blood-producing hematopoietic stem cells (HSCs).
The current roadblocks to HSC therapies include the rarity of matched donors for bone marrow transplant, engraftment failures, common shortages of donated blood, and the inability to expand HSCs ex vivo in large numbers. These major obstacles would cease to exist if an extensive, bankable, inexhaustible, and patient-matched supply of blood were available. The recent validation of hemogenic endothelium (blood vessel cells lining the vessel wall that give rise to blood stem cells) has introduced new possibilities in HSC therapy. Thus, the inventors aimed to understand the requirements for the process of endothelial to hematopoietic transition and to re-engineer mature human endothelium into blood-producing blood HSCs.
Engineering functional HSCs from mature endothelium may present the following advantages:
Scientists at the University of California, San Francisco have developed a system for reprogramming endothelial cells into blood like cells (being evaluated currently for bona fide blood-producing HSC activity) using episomal non-integrating vectors. They envision long-term banking of endothelial cells (which can be kept at -80°C conditions), indexed with HLA subtypes and other phenotype analysis important for transplantation, comprising a large database. When a bone marrow transplant is needed and matched against the endothelial database, then the endothelial cell line is thawed and reprogrammed into HSCs for transplantation using this novel approach.
To develop and commercialize this technology as an alternative source of patient-matched blood
|Patent Cooperation Treaty||Reference for National Filings||WO2016201133||12/15/2016||2015-230|