Hematopoietic Stem Cell & Cellular Therapy Lab

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With the aim of enhancing and expediting haematopoietic recovery after haematopoietic stem cell transplantation (HSCT) or high-dose chemotherapy, our research focuses primarily on the expansion of quality haematopoietic stem and progenitor cells (HSPC) to achieve therapeutic dosage. We have generated a small molecule that has the capacity to expand blood stem cells efficaciously. The observed expansion can significantly improve the outcome of haematopoietic blood stem cell transplants, especially cord blood transplants. Interestingly, this small molecule contributes to the growth of the most primitive blood stem cells while suppressing the growth of leukaemic cells, highlighting its potential for use in accelerating hematopoietic recovery with simultaneous leukaemia control. To date, we have demonstrated the reproducibility of our small molecule based HSPC expansion under different laboratory settings - both locally and with international collaborators. Further, our team is interrogating how this specific small molecule has the capacity to expand HSPCs with minimal toxicity to cells. Namely, identifying the binding partners of the small molecule as well as pathways that it influences, with the objective of generating a better understanding of HSPC growth and development. To further enhance the effect of the small molecule-based system in expanding HSPCs, our new area of work is focusing on the exogenous usage of extra-cellular matrix proteins such as laminins that would mimic the HSPC niche microenvironment and thereby enable effective expansion of HSPCs from adult sources such as mobilized peripheral blood and bone marrow.

Selected publications:

1. Bari S, Zhong Q, Fan X, et al. Ex vivo expansion of CD34+CD90+CD49f+ hematopoietic stem and progenitor
   cells from non-enriched umbilical cord blood with azole compounds. Stem Cells Transl Med. 2018 May;7(5):376-393.
2. Fan X, Guo D, Cheung AMS, et al. Mesenchymal Stromal Cell (MSC)- Derived Combination of CXCL5 and Anti-CCL24 Is Synergistic and Superior to MSC and Cyclosporine for the Treatment of Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2018. doi:https://doi.org/10.1016/j.bbmt.2018.05.029.
3. Bari S, Chu PPY, Lim A, et al.Mitochondrial superoxide reductionand cytokine secretion skewing by carbon nanotube scaffolds enhance ex vivo expansion of human cord blood hematopoietic progenitors. Nanomedicine. 2015;1:1643–1656.
4. Bari S, Seah KKH, Poon Z, et al. Expansion and homing of umbilical cord blood hematopoietic stem and progenitor cells for clinical transplantation. Biol Blood Marrow Transplant. 2015;21:1008–1019.
5. Fan X, Gay FPH, Lim FWI, et al. Low-dose insulin-like growth factor binding proteins 1 and 2 and angiopoietin-like protein 3 coordinately stimulate ex vivo expansion of human umbilical cord blood hematopoietic stem cells as assayed in NOD/SCID gamma null mice. Stem Cell Res Ther. 2014;30;5:71.