Neurosciences - Stem Cell Group

Juliana Lamoury, Ph.D., Francois Lamoury, CNAM, and Bruce J. Brew, MBBS MD FRACP
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Broad Research Areas: Neurology, Neuroscience

Specific Research Terms: Neurodegenerative disorders, kynurenine pathway (KP) of tryptophan metabolism, multiple sclerosis (MS), adult mesenchymal and neural stem cells.

Research Interests:

Adult stem cells derived from brain and marrow tissues: i) investigation of differentiation of stem cells into neural cells; ii) examination of the potential of bone marrow- and brain-derived cell transplantation as a treatment for multiple sclerosis, neurodegenerative and genetic disorders that result in demyelination. Collaboration exists with centres in the USA, Germany, Japan, Melbourne and University of Sydney.

Program description:

1. Adult stem cells and their application to neurodegenerative disorders.

2. Tryptophan metabolism in stem cell biology and neurogenesis.

3. Role of chemokines in adult stem cell migration.

1. Adult stem cells and their application to neurodegenerative disorders.

The cause of multiple sclerosis is unknown but it is thought most likely to be a consequence of an autoimmune process. The disorder is characterised most often by a relapsing remitting course that over time transforms into a chronic slowly progressive disease without remissions. It is postulated that the remissions are related to the presence of oligodendrocyte precursors that can differentiate into oligodendrocytes and lead to remyelination. Over time the "pool" of oligodendrocyte precursors becomes exhausted and so the disease becomes progressive. Our group is in the process of differentiating human and mouse brain and marrow derived stem cells into neural cells including oligodendrocytes for transplantation into mouse models of demyelination to determine their efficacy in amelioration of disease.

2. Tryptophan metabolism in stem cell biology.

In relation to the effects of interferon beta and copolymer-1 on MSC neural differentiation, we have shown that both bone marrow- and brain-derived stem cells express the full complement of enzymes in the kynurenine pathway (KP) of tryptophan metabolism. We have shown that the KP in stem cells can be induced by interferon beta. Such induction is known to lead to significant depletion of tryptophan in the cellular milieu, which in turn is now known to compromise rapidly dividing cells with consequent impairment of differentiation. These data are now being prepared for publication. Hence this project has established an essential platform upon which further stem cell transplant studies can be built. Moreover, the KP results provide a unique mechanism whereby stem cell division and differentiation can be significantly enhanced.

3. Role of chemokines in adult stem cell migration.

The use of adult stem cells for therapeutic substitution in neurodegenerative diseases assumes the ability of precursor cells to migrate to lesion sites and provide trophic support and/or functional replacement of damaged neural cells. For such therapeutic strategies to be effective, it is critical to have a thorough understanding of the signals in the stem cell microenvironment that provide cues to control their recruitment and migration. This study should determine which chemokine(s) are optimal in promoting migration to the brain of stem cells. Moreover, it will establish whether commonly used MS therapies may be able to enhance stem cell selection and migration. Finally, it will establish whether such therapies can enhance stem cell migration into damaged areas. The results will have wide applicability to other stem cell therapies.