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There has been significant interest in the potential of autologous haematopoietic stem cell transplantation (AHSCT) to improve clinical outcomes for people living with MS. AHSCT has been shown in previous research, including studies conducted by researchers at St Vincent’s Hospital in Sydney, to “re-set” the immune system, possibly leading to disease remission and better outcomes for people living with MS. However, the type of individual most likely to benefit from AHSCT is still being determined.
St Vincent’s Hospital in Sydney is one of the leading hospitals performing AHSCT in MS in Australia and has a strategic partnership with MS Australia to advance cellular therapies such as AHSCT. St Vincent’s Hospital also has a biobank of blood samples collected from people living with MS over time, both before and after the AHSCT procedure.
Dr Malini Visweswaran and her team hope to shed light on how AHSCT induces the benefits seen in MS. Current thinking is that changes to the metabolic state of immune cells may be important in this process. This concept will be investigated in this study by closely examining the metabolic profile of immune cells to see how the transplant affects their metabolism.
The research team has access to the biobank of blood samples and clinical progress reports of past patients and can match the laboratory results to clinical outcomes to gain an even deeper understanding of the procedure.
By understanding these underlying mechanisms, it is hoped that safer and more effective transplant options may be developed. Furthermore, it will enhance understanding of the processes contributing to a successful AHSCT outcome and the best candidates for the procedure in people living with MS.
Dr Visweswaran and her team completed the experiments to determine the immune and metabolic characteristics of a type of blood immune cell (peripheral blood mononuclear cells (PBMCs)) from people with MS, people with non-Hodgkin’s lymphoma and from people without these conditions. She and her team have started analysing further characteristics of PBMCs.
So far, Dr Visweswaran and her team have shown how strongly five key metabolic proteins are produced by PBMCs from the three study groups. They found a substantial upsurge in these metabolic proteins during the early post-transplant period following AHSCT. In particular, T-regulatory cells and CD56hi natural killer cells (types of immune cells) showed increases in all five metabolic proteins during this early post-transplant period. However, the T-conventional cells were the only subset of cells that had a sustained an increase in markers related to mitochondrial respiration (a way of making energy based on oxygen) up to 24 months after AHSCT. Put together, the increased metabolic activity immediately after AHSCT may reflect increased immune cell production and that T-conventional cells prefer to use an energy-efficient metabolic method via their mitochondria at later periods following AHSCT.
Over the next 12 months, Dr Visweswaran and her team will continue to study the characteristics of PBMCs, analysing the data already collected and conducting further experiments.
Updated 31 March 2024
$165,000
2021
3 years
Current project
