Expansion of Umbilical Cord Blood with Small Molecule


PATENT STATUS

The Application is in National Phase in ten countries including US, EU, China and Singapore.


OVERVIEW OF TECHNOLOGY ON OFFER

Substituted azole derivatives for generation, proliferation and differentiation of hematopoietic stem and progenitor cells.


BRIEF DESCRIPTION

The technology is jointly owned by National University of Singapore (NUS) and Singapore Health Services Pte Ltd (SingHealth) and is directed to the method for ex vivo expansion of the total nucleated cells (TNC) and/or the subset of the CD45+CD34+ hematopoietic stem cells and progenitor cells (HSPC) component of an umbilical cord blood, bone marrow and/or mobilized peripheral blood stem cell sample, using an azole-based small molecule. 

The UCB is immunologically superior for following reasons: 

  • Greater tolerance for HLA mismatch
  • Easier to find a match, particularly for ethnic minorities
  • Reduced GVHD
  • Lower incidence of relapse
  • Readily available, tested, no donor attrition


But it is limited by low cell numbers, which in turn leads to fewer donor units suitable for use, slower haematopoietic recovery and susceptibility to fatal infections. Given the advantages of using UCB, it is therefore desirable to find a way to increase the number of TNC and HSPC prior to transplanting in adults, so as to enable UCB to be a graft of primary choice for Hematopoietic stem cell transplantation (HSCT).

The small molecule (C7) used in our technology can expand UCB HSPC without the need to perform prior CD34+/CD133 based stem cell enrichment. However, if CD34 selection is further employed, this molecule is also able to attain superior HSPC expansion compared to current technologies. 
The expanded UCB graft retains in vivo functionality and expands rare population of stem cells: CD90 and CD49f. 

The researchers are currently establishing Phase I/II Clinical Trial Protocol. 


POTENTIAL APPLICATIONS

Use of small molecule to expand banked cord blood stem cells (pre-culturing may not be required) to generate sufficient quantity for adult patients while maintaining their quality. 

Transplant patients may be suffering from, for example blood cancers, thalassemia, auto-immune diseases. 


KEY BENEFIT

The C7 expanded grafts retain both phenotypic markers and the ability to support early human cell engraftment in NOD/SCID gamma (NSG) and contribute to long-term bone marrow hematopoiesis.


PUBLICATION

Ex Vivo Expansion of CD34+CD90+CD49f+ Hematopoietic Stem & Progenitor Cells from Non-enriched Umbilical Cord Blood with Azole Compounds.

Publication date May 2018  publication description Stem Cells Transl Med. 2018 May;7(5):376-393. doi: 10.1002/sctm.17-0251. Epub 2018 Feb 2


INVENTOR BIO

Prof. William Hwang
Dr. Sudipto Bari


CONTACT

Please email us for further enquiries: cted@duke-nus.edu.sg