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Compositions and Methods for the Expansion of Stem Cells

Detailed Technology Description
This invention provides an engineered degradation-resistant HOXB4 protein, materials and methods to produce it, and methods to use this recombinant protein for the ex vivo expansion of hematopoietic stem cells.
  • Improvedex vivo expansion of adult hematopoietic stem cells by overcoming CUL4-mediateddegradation of HOXB4. Blood, 2013, 121, 4082-9.

Hematopoietic stem cell (HSC) transplantation is used for treatment of hematologic diseases, but often the number of available immune-matched HSCs is insufficient for a successful transplant. Ex vivo expansion of HSCs could improve transplantation outcome.


HOXB4 protein can stimulate HSC expansion ex vivo and in vivo. Direct protein transduction of recombinant HOXB4 protein dramatically stimulates HSCs expansion without the induction of malignancies. However, the short half-life of HOXB4 protein necessitates frequent re-supply of the protein.


Dr. Pengbo Zhou at Cornell discovered that the HOXB4 protein is post-translationally regulated by the Cul4 ubiquitin ligase and defined the degradation signal sequence (degron) of HOXB4. A change of 3 key amino acid residues in the degron profoundly stabilizes the HOXB4 protein. Direct transduction of the degradation-resistant HOXB4 protein significantly enhances adult human HSC maintenance both in vitro and in vivo.


This technology overcomes a major technical hurdle in the ex vivo expansion of adult HSCs and progenitor cells for research and therapeutic use.


Potential Applications

  • Reagent for ex vivo expansion of adult HSCs
  • Ex vivo expansion of HSCs for therapeutic use



  • Requires significantly less protein during ex vivo HSC expansion
  • Fewer donor stem cells needed for therapeutics
  • No malignancy risk, unlike using a viral delivery method
Dan-Oscar Antsonda429@cornell.edu212-746-1297

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