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Hematopoietic stem cell transplant (HSCT) is able to treat a range of malignant and benign blood/bone marrow (BM) disorders e.g. leukaemia, lymphoma and thalassemia. It also remains as a last line of treatment for patients with advanced or refractory BM diseases and for those who have failed to respond to chemotherapeutics. BM and peripheral blood stem cells (PBSCT) remain as traditional graft sources for HSCT, but umbilical cord blood (UCB) grafts has emerged as a superior alternative for being safer and its immediate availability. There are currently >160 public UCB banks worldwide with an estimated 730,000 UCB units. However, the clinical application of UCB graft is constrained by limitations associated with insufficient total nucleated and stem cell cell dosage. Insufficient cell dose increases the neutrophil recovery times and thereby increases transplant-related mortality. Hence, overcoming the limited cell dosage problem of UCB grafts by performing ex vivo expansion of hematopoietic stem and progenitor cell (HSPC) could increase the clinical utility of UCB for adult HSCT.

Using a proprietary methodology involving azole small molecules, the research team has demonstrated improved expansion of UCB HSPCs that has no detectable leukemic transformation, but retains the phenotype and functional ability of the HSPCs in the graft. Preliminary results indicate sub-lethally irradiated NOD/SCID Gamma (NSG) mice transplanted with such expanded human HSPCs showed better engraftment in peripheral blood and BM thereby contributing to long-term haematopoiesis.

Project Deliverables

The project aims to (i) complete pre-clinical testing (ii) optimize scale-up protocol for automated cell product manufacturing device in a GMP facility and (iii) evaluate stability, potency, safety and sterility of the expanded UCB grafts thereby completing necessary work to initiate a phase I/II clinical trial.

Principal Investigator: Prof William HWANG

Institution: National Cancer Centre Singapore

NHIC Ref: NHIC-I2D-1506047



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