T-018886 — Scalable Generation of Hematopoietic Progenitors from Human Pluripotent Stem Cells

Technology Description

In vitro generation of CD34⁺ hematopoietic progenitor cells (HPC) that faithfully recapitulate in vivo behavior is an area of ongoing research. A key characteristic of CD34⁺ HPCs obtained from both embryos and adults is their dependence on retinoic acid (RA) signaling. However, HPCs obtained by existing in vitro methods from human pluripotent stem cells (hPSCs) are RA-independent. Researchers at Washington University and San Raffaele Telethon Institute have discovered a novel in vitro method for the generation of RA-dependent HPCs from hPSCs. RA supplementation to a critical sub-population and a temporally restricted stage of hPSC differentiation was found to significantly enhance hematopoiesis potential, and suggested the presence of a CD34⁺, HSC-competent population in the bulk culture.

Left: Hematopoiesis potential of RA-dependent (RAd) hemogenic endothelium was significantly higher than RA-independent (RAi) HE. Middle: Supplementation of RA (ROH) at Day 3 of hPSC differentiation resulted in significantly more multi-lineage hematopoiesis. Right: Murine xenografts showed that CD34⁺ cells (RAd) obtained by this method could persist temporary in vivo whereas conventional RAi cells completely failed to graft in neonatal mice.

Stage of Research

Validated protocol/culture media for commonly used hPSC lines, such as H1, H9, and iPSC1.

Applications

• Generation of CD34⁺, RA-responsive HPCs that harbor definitive erythroid, myeloid, and lymphoid hematopoietic potential.
• Synthetic blood cell production for replacement therapy or off-the-shelf immunotherapy, as well as for research use only purposes.

Key Advantages

• High yield, scalable production of synthetic blood products from hPSCs compared to other published methods.

Patents: Patent pending, EU, CA and US rights available; see WO2020154412A1.

Related Web Links: Nat Cell Biol. 2022 May; 24(5): 616–624

Christopher Sturgeon lab and bio | Andrea Ditadi lab and bio