An Optimal Bioreactor For Production Of Erythrocytes From Human Embryonic Stem Cells

Funding Type: 
SEED Grant
Grant Number: 
RS1-00183
ICOC Funds Committed: 
$0
Disease Focus: 
Vascular Disease
Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
A reliable, reproducible, clinically safe and cost effective technology for generating therapeutically relevant quantities of red blood cells from human embryonic stem cells (hESC) has potential to have a profound clinical significance on the blood supply in the clinics. This is a proposal to develop such a bioreactor with optimal conditions for production of erythrocytes from hESCs based on our recent lab-scale culture conditions. Production of large quantities of mature red blood cells from human ES cells represents, in principle, a limitless source for erythrocyte transfusions. Some patient populations, such as Sickle cel Disease and Thalassemia require frequent blood transfusions and allosensitization to minor (non ABO/RhD) antigens is quite frequent (5 to 35%). In particular , allosensitization is of special concerns in the treatment of sickle cell accuse of significant disparities in the prevalence of variety of non ABO/RhD blood antigens between the donor pool (typically white) and the patient population (typically of African descent). Generation of ES-derived ORh-negtive blood products on a large scale will allow to avoid these problems and create banks of safe blood products, independent of donors, for transfusion medicine needs. This will be especially useful for rare red blood-cell types with limited donor availability. In addition, with possible design of improved universal donor erythrocytes with a limited antigenic repertoire through genetic manipulation will have tremendous clinical significance. In the clinical settings, hES cell–derived erythrocytes would offer a number of superiorities over packed red blood cells (PRBC) currently used in clinical practice. These cells will: 1) have a greatly reduced risk of infection, 2) be a cohort of young cells that will have longer in vivo lifespan, excellent oxygen transport function and improved intravascular survival, 3) be always available, 4) be type O, Rh(D) negative and of a phenotype selected to minimize the risk of a hemolytic reactions, 5) be convenient to use. The generation of universal blood donor-banks will require automated system of production and strategies to increase efficacy of this process, which is the goal of the proposed work.
Statement of Benefit to California: 
There has recent alarms on chronic shortage of safe blood and blood products and recommendations on new strategies to prevent transmission of HIV and other blood-borne pathogens, such as collecting blood only form donors at the lowest infectious risk (reports of Fifty-Eighth World Health Assembly in May of 2005). It is also proposed to introduce legislation to eliminate paid blood donation “expect in limited circumstances of medical necessity”. Production of large quantities of mature red blood cells from human ES cells represents, in principle, a limitless source for erythrocyte transfusions. Some patient populations, such as Sickle cel Disease and Thalassemia require frequent blood transfusions and allosensitization to minor (non ABO/RhD) antigens is quite frequent (5 to 35%). In particular , allosensitization is of special concerns in the treatment of sickle cell accuse of significant disparities in the prevalence of variety of non ABO/RhD blood antigens between the donor pool (typically white) and the patient population (typically of African descent). Generation of ES cell-derived ORh-negtive blood products on a large scale will allow to avoid these problems and create banks of safe blood products, independent of donors, for transfusion medicine needs. The generation of universal blood donor-banks will require automated system of production and strategies to increase efficacy of this process. This is a proposal to develop such a bioreactor with optimal conditions for production of erythrocytes from hESCs based on recent success achieved in lab-scale culture conditions. If successful, this would provide tremendous advantages for the State-of –California: unlimited supply of safe blood, ability to produce blood with specific, low antigenic phenotypes for transfusions in patients with b-thalassemia and Sickle Cell Anemia. Since Bay Area, specifically Oakland has a very large Sickle Cell and Thalassemic population, the economic and health advantages will be enormous.

© 2013 California Institute for Regenerative Medicine