Development of an automated Umbilical Cord Blood Hematopoietic Stem Cell expansion by endothelial cells for transplantation

Period of Performance: 09/01/2015 - 08/31/2016


Phase 1 SBIR

Recipient Firm

Angiocrine Bioscience, Inc.
New York, NY 10065
Principal Investigator


DESCRIPTION (provided by applicant): Initially, umbilical cord blood (UCB) transplantation was limited to children, given the low cell dose infused. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic diseases in the pediatric setting. In more recent years the use of UCB transplants has expanded and results for adult umbilical cord blood transplantation have improved, but not without a number of challenges. As little as 10% of the world-wide inventory of UCB may be of insufficient total nucleated cell count (TNC) for both adult and pediatric transplants. The minimal TNC count results in a profound delay in recovery of the patients leaving them susceptible to numerous lethal complications. In order to realize the full potential and impact UCB can have for patients treated for hematological malignancies, ex vivo expansion of the UCB material is necessitated. Current mechanisms for the expansion of Hematopoietic Stem and Progenitor Cells (HSPCs) lack the proper microenvironment, possibly explaining the clinical trial failures. Evidence continues to mount from numerous groups detailing the indispensable role endothelial cells (ECs) have in promoting the HSPC via the secretion of numerous growth factors, termed angiocrine factors. Traditional mechanisms of culturing endothelial cells have not been permissible to recapitulate the in vivo microenvironment generated by ECs. This limitation has been eliminated in ECs by the VeraVec EC platform by the addition of the Ad5 E4ORF1 protein. VeraVec ECs have repeatedly demonstrated their capacity to expand HSPCs with high fidelity and high engraftability in co-culture conditions. Pre-clinical data demonstrates the capacity for the platform to expand UCB 1000-1800 fold over 12 days. Importantly, this expanded material maintains all aspect of the HSPC phenotype including long term engraftment, serial transplant, and multilineage commitment equal to unmanipulated UCB. However, large scale co-cultures of HSPCs and VeraVec ECs are labor intensive, logistically challenging, and consume large quantities of reagents in cGMP compliant facilities. These barriers make the adoption of the VeraVec EC platform for HSPC unlikely. We therefore propose to introduce the co- culture into the TerumoBCT Quantum hollow fiber bioreactor to automate the expansion. The end product will be an automated, large scale, high fidelity expansion without sacrificing any benefits of the VeraVec platform.