Hematopoietic progenitor cells (HPC) are multi-potent hematopoietic lineage cells that can differentiate into any type of blood cell, including but not limited to erythrocytes, T cells, B cells, and natural killer cells. As such, they have high therapeutic potential in the fields of regenerative medicine and cancer immunotherapy, especially when generated from patient-derived induced pluripotent stem cells (iPSC). Currently, the most efficient protocol to produce HPCs is co-culturing human iPSCs (hiPSC) with mouse stromal cells as a two-dimensional (2D) monolayer. However, animal cells are not suitable for clinical application and two dimensional (2D) cultures are not physiologically accurate. Further, animal product free (xeno-free) systems are expensive and not efficient.
Researchers at the National Cancer Institute (NCI) developed a novel approach to produce HPCs from hiPSCs using a human mesenchymal stem cell (hMSC) 3D co-culture condition. hiPSCs and hMSCs are first used to make spheroids, and then cultured in a 3D condition for two weeks. The inventors observed hematopoietic progenitor markers in hiPSCs cultured this way, indicating differentiation into HPCs. They also successfully adapted this protocol for use in bioreactors for mass production. This method is efficient, fast, cost-effective, and fully autologous; both hiPSCs and hMSCs may be derived from the same patient. HPCs can then be further differentiated into mature hematopoietic cells – such as T cells expressing a specific receptor to target cancer cells – used to reconstitute the whole immune system in patients with immunodeficiency.
The NCI seeks statements of capability or interest from parties interested in licensing this method of producing HPCs for treatment of hematopoietic disorders and/or regenerative medicine.