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Efficient Methods to Prepare Hematopoietic Progenitor Cells in vitro for Therapeutic Use

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Multi-potential hematopoietic progenitor cells (HPC) can differentiate into any class of blood cells, and are highly useful in regenerative medicine, immunology, and cancer immunotherapy. Current methods to generate HPCs are limited either due to the use of animal products, or the high cost and low efficiency of animal product free systems. Researchers at the National Cancer Institute (NCI) have developed a protocol to prepare HPCs from human induced pluripotent stem cells (hiPSC), using human mesenchymal stem cells (hMSC) in a three-dimensional (3D) co-culture condition. Thus, they are able to generate HPCs in a fully human, autologous system, which can be used to further generate immune cells for therapy. This protocol is adaptable to mass production by bioreactors. NCI seeks licensees for these methods of generating HPCs in a 3D co-culture with hMSCs to be used in a variety of applications such as treatment of blood disorders, regenerative medicine, and antibody production.
NIH Reference Number
Product Type
  • Hematopoietic Progenitor Cells, HPC, Induced Pluripotent Stem Cells, iPSC, hiPSC, 3D Culture, Human Mesenchymal Stem Cells, hMSC, Bioreactor, Immunotherapy, Vizcardo
Collaboration Opportunity
This invention is available for licensing.
Description of Technology

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.

Potential Commercial Applications
  • Treatment of hematopoietic disorders including leukemias, lymphomas, anemias, rare blood diseases, and infections
  • Immune system reconstitution after irradiation and chemotherapy, or in patients with immunodeficiencies
  • In vitro generation of any class of hematopoietic lineage cells, including therapeutic T cells from patient iPSCs
  • Generation of other hematopoietic products such as antibodies, cytokines, and human serum
Competitive Advantages
  • Fully human, autologous, high-efficiency, and cost-effective system
  • 3D culture creates a more physiological microenvironment
  • Mass production of HPCs and further differentiated cells in bioreactors

Raul Vizcardo Ph.D. (NCI), Naritaka Tamaoki Ph.D. (NCI), Meghan Good M.D. (NCI), Nicholas Restifo M.D. (NCI)

Development Stage

Vizcardo R, et al. Generation of tumor antigen-specific iPSC-derived thymic emigrants using a 3D thymic culture system.  [PMID 29562175]

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/583,240 , Filed 08 Nov 2017
  • PCT: PCT Application Number PCT/US2018/059856 , Filed 08 Nov 2018
Therapeutic Area
Wednesday, September 18, 2019