Pluripotent Cells Produce Hematopoietic Stem Cells and Natural Killer Cells
An innovative method produces hematopoietic stem cells (HSPCs) from human pluripotent stem cells (hESCs and iPSCs). Inducing hematopoietic differentiation of stem cells and treating them with an aryl hydrocarbon receptor (AHR) antagonist promotes early human hematoendothelial development and may improve HSPC production from hESCs and iPSCs for clinical applications. In addition to AHR antagonism, disrupting all or part of the AHR coding and/or promoter region in a stem cell reduces or even completely eliminates AHR expression. The methods also treat hESCs and iPSCs to induce natural killer (NK) cell differentiation: results show that AHR antagonism increased production of NK cells (CD45+CD56+ cells) from human pluripotent stem cells.
Hematopoietic Cell Transplantation Improvements
Using hESCs and iPSCs to develop transplantable HSPCs capable of long-term multi-lineage engraftment is a challenge. Previous attempts have used different stromal cell lines and agents such as dmPGE2 and Notch ligands, but in vivo engraftment of such cells remains limited. However, invitro analysis of this method showed that AHR antagonism increases HSPCs, thus showing promise as an important cell source for clinical applications such as hematopoietic cell transplantation. In addition, this technology may help to produce other therapeutic cells (NK cells, T cells, RBCs and megakaryocytes/platelets) from hESCs/hiPSCs.
BENEFITS AND FEATURES OF ARYL HYDROCARBON RECEPTOR (AHR) ANTAGONISM TO PROMOTE HEMATOENDOTHELIAL DEVELOPMENT:
- Aryl hydrocarbon receptor (AHR) antagonist promotes early human hematoendothelial development
- May improve HSPC production from hESCs and iPSCs for clinical applications
- AHR disruption can reduce or even completely eliminate AHR expression
- hESC and iPSC treatments induce both hematopoietic differentiation as well as NK cell differentiation
Phase of Development In vitro