Biologically active constituents of the secretome of human W8B2+ cardiac stem cells

Shuai Nie, Xin Wang, Priyadharshini Sivakumaran, Mark M.W. Chong, Xin Liu, Tara Karnezis, Nadeeka Bandara, Kaloyan Takov, Cameron J. Nowell, Stephen Wilcox, Mitch Shambrook, Andrew F. Hill, Nicole C. Harris, Andrew E. Newcomb, Padraig Strappe, Ramin Shayan, Damián Hernández, Jordan Clarke, Eric Hanssen, Sean M. DavidsonGregory J. Dusting, Alice Pébay, Joshua W.K. Ho, Nicholas Williamson, Shiang Y. Lim

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Abstract

The benefits of adult stem cells for repair of the heart have been attributed to the repertoire of salutary paracrine activities they appear to exert. We previously isolated human W8B2+ cardiac stem cells (CSCs) and found they powerfully influence cardiomyocytes and endothelial cells to collectively promote cardiac repair and regeneration. Here, the complexity of the W8B2+ CSC secretomes was characterised and examined in more detail. Using ion exchange chromatography to separate soluble proteins based on their net surface charge, the secreted factors responsible for the pro-survival activity of W8B2+ CSCs were found within the low and medium cation fractions. In addition to the soluble proteins, extracellular vesicles generated from W8B2+ CSCs not only exhibited pro-survival and pro-angiogenic activities, but also promoted proliferation of neonatal cardiomyocytes. These extracellular vesicles contain a cargo of proteins, mRNA and primary microRNA precursors that are enriched in exosomes and are capable of modulating collectively many of the cellular pathways involved in protein metabolism, cell growth, as well as cellular responses to stress and organisation of the extracellular matrix. Thus the W8B2+ CSC secretome contains a multitude of bioactive paracrine factors we have now characterised, that might well be harnessed for therapeutic application for cardiac repair and regeneration.
Original languageEnglish
Article number1579
Pages (from-to)1-12
Number of pages12
JournalScientific Reports
Volume8
Issue number1
Early online dateJan 2018
DOIs
Publication statusPublished - 01 Dec 2018

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    Nie, S., Wang, X., Sivakumaran, P., Chong, M. M. W., Liu, X., Karnezis, T., Bandara, N., Takov, K., Nowell, C. J., Wilcox, S., Shambrook, M., Hill, A. F., Harris, N. C., Newcomb, A. E., Strappe, P., Shayan, R., Hernández, D., Clarke, J., Hanssen, E., ... Lim, S. Y. (2018). Biologically active constituents of the secretome of human W8B2+ cardiac stem cells. Scientific Reports, 8(1), 1-12. [1579]. https://doi.org/10.1038/s41598-018-19855-4