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Research Interest:
Haematopoietic stem cell transplantation (HSCT) has been a useful modality of treatment for a wide variety of illnesses in the last few decades. Both the annual number of HSCT procedures has increased dramatically and the number of diseases for which HSCT is considered appropriate has expanded over the years. Estimates suggest that 30,000- 40,000 HSCT procedures are performed annually worldwide. In the Singapore General Hospital , nearly 1000 transplants have been performed.
Umbilical cord blood (UCB) has been used as a source of hematopoietic stem cells for transplantation for more than a decade. It has evolved from being an experimental procedure, to a viable alternative for patients with no other options, and currently, to a treatment measure on par with other more established options.
This coupled with the rapid availability of UCB and absence of donor risk makes UCBT an attractive option to unrelated donor HSCT. Furthermore, the robust proliferative potential, immunological naiveté, and multipotency of UCB stem cells provides promise that the use of UCB could extend well beyond current applications. Funded by the Singapore Cancer Syndicate, the National Medical Research Council and the Department of Clinical Research, SGH, Dr Hwang has developed laboratory-based, preclinical and clinical trials to expand the use of umbilical cord blood (UCB) for the treatment of haematological and non-haematological malignancies.
A. CLINICAL PROGRAM.
In our clinical program, we are exploring the use of Improved Haematopoietic Stem Cell Transplantation regimens and Umbilical Cord Blood Transplantation (UCBT) for the treatment of cancer. Specifically, we have developed a variety of platforms and protocols for Haematopoietic Stem Cell Transplantation. These include:
- Clinical UCB transplant protocols. This trial is ongoing
- Ex-vivo expansion clinical trials for the treatment of haematological malignancies. We expect to commence clinical trials for this in 2009 .
- Intra-bone marrow delivery of hematopoietic stem cells for transplantation. We have completed animal studies and are exploring the possibility of clinical trials .
B.CELLULAR ENGINEERING PROGRAM.
In our cellular engineering program we are exploring the feasibility of stem cell selection and the expansion of various subsets of cord blood stem cells. The program will include:
- Laboratory studies on Ex-vivo Cord Blood Expansion. We have explored the manipulation of UCB and BM cells in-vitro (Hwang, Blood 2002 abstr; Sun, SGH Proc 2004), and in the engineering of these cells for therapy (Hwang, Ann Acad Med 2004). A combination of cytokines and antibodies has been found to expand naïve progenitors while depleting mature cells from cord blood cultures resulting in a higher percentage of immature CD34 positive cells and megakaryocytic progenitors .
- Development of UCB anti-tumor donor lymphocyte infusions (DLI). One disadvantage of UCBT is the lack of ability to take further stem cells or lymphocytes from donor for use as donor lymphocyte infusions for disease control. While the efficacy of DLI is limited to certain diseases like chronic myeloid leukemia, the ability to generate DLI from cord blood would overcome perceptual barriers to UCBT
- Development of intra-bone marrow cord blood transplants (an in vivo cord blood expansion protocol). This study was published in Experimental Hematology 2008 .
C.CORD BLOOD BANKING PROGRAM.
Dr Hwang is holds a concurrent appointment as Medical Director of the Singapore Cord Blood Bank (SCBB) which has been established with the chief aim of providing UCB units for transplantation. The Singapore Cord Blood Bank is supported by Singapore Health Services (SingHealth), the National Healthcare Group, the Children's Cancer Foundation and Club Rainbow. It seeks to promote the use of cord blood stem cells for research and will collaborate with and supply cord blood stem cells to many members of the Stem Cell Network. The SCBB has begun collection of UCB samples since December 2004 and is currently a full-fledged member cord blood bank with the US National Marrow Donor Program. Some areas of focus, which will be better defined later, include:
- Correlation between maternal characteristics and the volume, cell count and viability of stem cells of the cord blood units collected. Better identification of optimal cord blood units prior to UCB collection will greatly improve the cost-effectiveness of any UCB collection strategy.
- Improvements in cord blood collection techniques for optimisation of stem cell yield.
- Correlations will be made between transplant centre outcomes with the UCB cell dose, HLA and the presence of Kir mismatches.
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