Hematopoietic Stem Cell & Cellular Therapy Lab

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Our research has focused on expanding or replacing the role of haematopoietic and mesenchymal stromal cells to enhance haematopoietic recovery after high-dose chemotherapy and transplantation as well as for the treatment of autoimmune disease.

We have developed a small molecule that can expand blood stem cells effectively and that could significantly improve the outcome of haematopoietic blood stem cell transplants, especially cord blood transplants. Interestingly, this molecule appears to encourage the growth of the most primitive blood stem cells while suppressing the growth of leukaemia cells, suggesting a potential for use in accelerating haematopoietic
recovery with simultaneous leukaemia control.

In addition, we have also developed a two-factor (2F) combination that can effectively treat graft versus host disease as well as autoimmune disease in mice. These technologies have been patented and we are currently looking to bring both treatments to clinical trials.

Finally ongoing studies have also recently identified a new role for the stromal microenvironment in the pathogenesis and disease progression of myelodysplastic syndromes, a pre-leukaemic disorder of the bone marrow. This could provide the basis for the introduction of new cancer drugs that target the stromal microenvironment and the means for identifying patient populations that may benefit from such therapy.

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.