A paradigm shift in the management of future cardiovascular risk following hypertensive disorders in pregnancy using mini-hearts and patient-derived stem cells

Project Member(s): McClements, L., Gallego Ortega, D., Gentile, C., McGrath, K.

Funding or Partner Organisation: Maridulu Budyari Gumal - The Sydney Partnership for Health, Education, Research and Enterprise (SPHERE) (Maridulu Budyari Gumal - The Sydney Partnership for Health, Education, Research and Enterprise)
Maridulu Budyari Gumal - The Sydney Partnership for Health, Education, Research and Enterprise (SPHERE) (Maridulu Budyari Gumal - The Sydney Partnership for Health, Education, Research and Enterprise)

Start year: 2022

Summary: ypertensive disorders in pregnancy (HDP) have been linked to increased risk of future cardiovascular disease (CVD), a number one killer for women. Although there is a well-established link, the mechanisms of this association are poorly understood. There is an urgent need for personalised models of CVD that can provide better insight into molecular mechanisms after HDP hence improving clinical management of high-risk women. For this reason, we have extensively studied how to mimic complex CVD using patient-derived cells for the creation of advanced cardiac laboratory tools. This resulted in the generation of cardiac spheroids (or “mini-hearts”). In collaboration with the clinicians from the P4 study (that follows women up to 5 years after HDP) at St George’s hospital, we have carried out a pilot study demonstrating that we can indeed generate patient-derived stem cells and mini-hearts from women’s peripheral blood. Therefore, our new approach will allow us to understand HDP-induced CVD better and develop personalised monitoring and treatment strategies. As part of this 6-month short-term major impact project, we aim to continue our exciting work with the P4 participants, five years after HDP. Once we generate these patient-derived multicellular cardiac spheroids or mini-hearts, we plan to carry out cardiac functional assays to assess differences at the cell level between stem cells-derived mini-hearts from HDP and healthy pregnancies. Single cell RNA sequencing will be also conducted for comprehensive characterisation and identification of therapeutic targets towards personalised treatment of women’s CVD.

Publications:

McClements, L, Liu Chung Ming, C, Pienaar, D, Ghorbanpour, S, Margaret Roberts, L, Henry, A, Kristine McGrath, D, Ortega, DG & Gentile, C 2024, 'New cardiac platform for the management of cardiovascular risk following preeclampsia using in vitro bioengineered cardiac spheroids and patient-derived stem cells', Elsevier BV, pp. 35-36.
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McClements, L, Pienaar, D, Chen, H, Gentile, C, Padula, M, McGrath, KC, Henry, A, Ghorbanpour, S, Margaret Roberts, L & Liu Chung Ming, C 2024, 'New 3D cardiac in vitro models for assessing the maternal cardiovascular health five years post hypertensive disorders of pregnancy', Elsevier BV, pp. 15-16.
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FOR Codes: Women's and maternal health, Specific population health (excl. Indigenous health), Biomedical engineering, Cellular interactions (incl. adhesion, matrix, cell wall), Regenerative medicine (incl. stem cells)

Acknowledgement of Country

UTS acknowledges the Gadigal people of the Eora Nation, the Boorooberongal people of the Dharug Nation, the Bidiagal people and the Gamaygal people, upon whose ancestral lands our university stands. We would also like to pay respect to the Elders both past and present, acknowledging them as the traditional custodians of knowledge for these lands.