Genetically engineered human fetal liver niche as platform for biomanufacturing of hematopoietic stem cells
AssigneeArizona Board of Regents on behalf of Arizona State University
InventorsMo Reza Ebrahimkhani, Jeremy Velazquez, Samira Kiani, Ryan Patrick LeGraw
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to methods for expanding populations of hematopoietic stem cells (HSCs) using a genetically engineered human fetal liver niche and compositions of purified ex vivo expanded HSCs. Also provided herein are methods of using such expanded HSC cell populations for clinical applications including allogeneic hematopoietic stem cell transplantation and for drug discovery and modeling human liver development.
Claims15
A method for ex vivo expansion of human hematopoietic stem cells (HSCs), the method comprising
- (a) contacting a cell population comprising the human HSCs with a synthetic fetal liver organoid comprising mesenchymal-like cells, CD34-expressing (CD34+) endothelial-like cells, desmin-expressing (DES+) stellate-like cells, and CEBPα+ hepatocyte-like cells, wherein at least a portion of cells of the synthetic fetal liver organoid are genetically modified to express one or more of Stem Cell Factor (SCF), FMS-like Tyrosine Kinase 3 Ligand (FLT3L), and Thrombopoietin (TPO);
- and
- (b) culturing the contacted organoid under conditions that promote proliferation of the human HSCs for about 3 to about 10 days, whereby an expanded population comprising CD34+ human HSCs is obtained.
A method for ex vivo expansion of human hematopoietic stem cells (HSCs), the method comprising
- (a) contacting a cell population comprising the human HSCs to a synthetic fetal liver organoid comprising mesenchymal-like cells, CD34-expressing (CD34+) endothelial-like cells, desmin-expressing (DES+) stellate-like cells, and CEBPα+ hepatocyte-like cells, wherein the synthetic fetal liver organoid is derived from embryonic stem cells (ESCs) or human pluripotent stem cells (hPSCs) engineered to express GATA6, wherein the cell population comprising the human HSCs are not derived from the engineered ESCs or hPSCs;
- and
- (b) culturing the contacted organoid under conditions that promote proliferation of the human HSCs for about 3 to about 10 days, whereby an expanded population comprising CD34+ human HSCs is obtained.
Dependencies are inferred from the claim text.