Stem cells have the potential to treat heart diseases by transforming into heart cells and blood vessels or by producing protective factors. The human heart cells produced from stem cells can be used to grow whole tissues of human heart, which might then be developed to replace and support damaged hearts through surgical transplantation, and to test new heart attack drugs.
In order to utilise human stem cells to treat heart disease effectively, our lab has a multidisciplinary approach to enhance stem cell cardiomyogenesis, improve survival and functionality of stem cell-derived heart cells, and optimise their delivery to the damaged heart. Studies include identify suitable stem cell sources, cardiac differentiation, stem cell secretomes, cytoprotective, tissue assembly and transplantation strategies.
Moreover, we have successfully developed a human heart model in the dish using human heart cells generated from patient-specific stem cells. This human heart model has allowed us to test new drugs that have potential to protect the heart from injury, and to study genetic mutations that can cause heart disease.
Cardiac stem cell therapy has great potential for repair of ischaemic heart disease. We have recently identified a new population of human cardiac stem cells which are positive for W8B2 antigen and it shows better cardioreparative benefit in vitro than do other adult stem cells from non-cardiac tissues. This benefit has been attributed to their secretion of cytokines, growth factors mRNA and miRNA (the secretome). We aim to explore the cardioreparative secretome constituents (growth factors, cytokines, extracellular vesicles and exosomes) of W8B2+ cardiac stem cells and to harness their paracrine activities to treat ischaemic heart disease.
Zhang Y, Sivakumaran P, Newcomb AE, Hernandez D, Harris N, Khanabdali R, Liu GS, Kelly DJ, Pébay A, Hewitt AW, Boyle A, Harvey R, Morrison WA, Elliott DA, Dusting GJ, Lim SY. Cardiac repair with a novel population of mesenchymal stem cells resident in the human heart. Stem Cells. 2015:33:3100-3113.
Khanabdali R, Rosdah A, Dusting GJ, Lim SY. Harnessing the secretome of cardiac stem cells as therapy for treat ischaemic heart disease. Biochem. Pharmcol. 2016 (Epub Feb 21)
Mitochondrial shape change (fusion or fission) allows them to maintain their integrity and efficient bioenergetics of the organelle, as well as influencing cell survival and differentiation. We aim to evaluate whether new drugs that regulate mitochondrial shape (i) enhance stem cell survival, and (ii) promote stem cell differentiation into cardiac lineage.
Rosdah AA, Holien JK, Delbridge LMD, Dusting GJ, Lim SY. Mitochondrial fission – a drug target for cytoprotection or cytodestruction? Pharmacol. Res. Prespective. 2016:4:e00235
Ong SB, Subrayan S, Lim SY, Yellon DM, Davison SM, Hausenloy DJ. Inhibiting mitochondrial fission protects the heart against ischemia reperfusion injury. Circulation. 2010:121: 2012-2022.
Pluripotent stem cells can provide an unlimited source of functional human cardiomyocytes for drug discovery and pharmacological safety testing, especially induced pluripotent stem cells which are generated by reprogramming adult somatic cells (such as skin cells). This allows for autologous patient-specific stem cells, and subsequently cardiomyocytes to be derived in a large scale to assess patient-specific drug responses (personalised medicine). These human cardiomyocytes can also be used to engineer 3D vascularized human heart tissue for transplantation to replace and support the infarcted myocardium.
Lim SY, Sivakumaran P, Crombie D, Dusting GJ, Pébay A, Dilley RJ. Trichostatin-A enhances differentiation of human induced pluripotent stem cells to cardiogenic cells for cardiac tissue engineering. Stem Cells Transl. Med. 2013:2:715-725
Chan EC, Kuo SM, Kong AM, Morrison WA, Dusting GJ, Mitchell GM, Lim SY*, Liu GS*. Three dimensional collagen scaffold promotes intrinsic vascularisation for tissue engineering applications. Plos one. 2016:11(2):e0149799.
Lim SY, Hernández D, Dusting GJ. Growing vascularised heart tissue from stem cells. 2013. J Cardiovasc Pharmacol. 2013:62:122-129.