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 | Research Interests |  |
| 2008 - 2012
| Fetal Mesenchymal stem cell biology |
| | Fetal mesenchymal stem cells (fMSC) have therapeutic potential, being more primitive than adult MSC with greater differentiability, but lack the oncogenicity of embryonic cells. They are readily isolated from placenta, amniotic fluid, fetal blood, liver and bone marrow. Our group showed that fMSC express pluripotency markers, grow faster and senesce later with longer telomeres, and show greater myogenic/osteogenic capacity. fMSC express adhesion molecules favouring engraftment, and their transplacental passage is implicated in fetomaternal microchimerism (FMC), whereby fMSC persist lifelong in women to participate in post-reproductive tissue repair. Intrauterine transplantation holds promise to treat disabling early-onset genetic disease, and we showed experimentally that a single MSC transplant in mid gestation prevents 2/3 of fractures in osteogenesis imperfecta. 1. Characterise novel properties of fetal MSC. To compare fMSC to later developmental and adult stem cells, we explore stability, transcriptional regulation, immunology and drivers to differentiation of fMSC under varying conditions though to senescence. Niche effects are explored as by site of origin and gestation. 2. Role of microchimeric fMSC in postreproductive tissue repair. To investigate the role of fMSC in tissue repair in women, the cell type will be delineated by in-vivo tracking with bioluminescent reporters. Transgenic models are used to investigate their functional role in acute and chronic maternal tissue repair. We are also exploring the biological role of and influence of pregnancy complications on FMC in health and disease. 3. Develop intrauterine transplantation for early onset genetic disease.Site-specific engraftment and tissue repair is being optimised in models with fetal tissue injury in utero, specifically osteogenesis imperfecta, and extended to other clinically-applicable models of debilitating hereditary disease. The aim is to develop fetal-fetal transplantation for translation into affected human pregnancies. 4. Optimise homing & site specific engraftment. The contribution of chemokine/receptor systems in fMSC homing to injured tissue, will be evaluated by manipulating receptors in a variety of tissue and bone injury paradigms. This will inform therapeutic strategies to facilitate stem cell uptake. | | Links: | Experimental Fetal Medicine Group 2007, http://www1.imperial.ac.uk/medicine/research/researchthemes/reprodscience/expfetalmedicine/ |
| Keywords: | Stem cells, transplantation, osteogenesis imperfecta, fetal development, microchimerism |
| | 2008 - 2012
| Monochorionic intertwin transfusion syndrome |
| | This clinical program investigates the fetoplacental circulatory pathophysiology and treatment of twin-twin transfusion syndrome. This is a debilitating fetal condition, which arises from unbalanced transfusion along placental vascular anastomoses in monochorionic or single placenta twins where a net recipient develops volume overload and polyuria and a net donor growth restriction, oliguria and fetal compromise. Despite advances in treatment TTTS still results in a high rate of fetal death or long term brain injury. Although considered rare, TTTS affects nearly as many babies as Down syndrome. Integrated clinical and laboratory research explores the molecular regulation of discordant vasoactive mediators, particularly the renin angiotensin system, in genetically identical twins. The aim is to develop better biomarkers to predict outcome, and explore the possibility of medical therapy. Clinical research centres around our endoscopic laser program in the Royal Brisbane & WomenÕs Hospital, where we are conducting clinical trials to determine the optimal nature and timing of treatment for early stage disease. This aims to answer the question whether a conservative approach to minimal disease allows many cases to resolve spontaneously without the risk of fetal death from treatment, or does definitive laser treatment at the outset reduce the risks of progressive disease and lead to an overall better outcome. | | Links: | Experimental Fetal Medicine Group 2007, Richard and Jack Wiseman Trust |
| Keywords: | Monochorionic twins, twin twin transfusion syndrome, endoscopic laser, radiofrequency ablation, renin angiotensin system, fetal physiology |
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