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. Davidson; Gregory J. Dusting; Alice Pébay; Joshua W.K. Ho; Nicholas Williamson; Shiang Y. Lim

doi:10.1038/s41598-018-19855-4

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^*

^*Corresponding author for this work

Vascular Biology

Research output: Contribution to journal › Article › peer-review

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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 language	English
Article number	1579
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-19855-4
Publication status	Published - 1 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), Article 1579. https://doi.org/10.1038/s41598-018-19855-4

@article{672344e70ecf47d48db95a004566f62d,

title = "Biologically active constituents of the secretome of human W8B2+ cardiac stem cells",

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.",

author = "Shuai Nie and Xin Wang and Priyadharshini Sivakumaran and Chong, {Mark M.W.} and Xin Liu and Tara Karnezis and Nadeeka Bandara and Kaloyan Takov and Nowell, {Cameron J.} and Stephen Wilcox and Mitch Shambrook and Hill, {Andrew F.} and Harris, {Nicole C.} and Newcomb, {Andrew E.} and Padraig Strappe and Ramin Shayan and Dami{\'a}n Hern{\'a}ndez and Jordan Clarke and Eric Hanssen and Davidson, {Sean M.} and Dusting, {Gregory J.} and Alice P{\'e}bay and Ho, {Joshua W.K.} and Nicholas Williamson and Lim, {Shiang Y.}",

note = "Funding Information: This work was carried out with support from the St Vincent{\textquoteright}s Hospital (Melbourne) Research Endowment Fund, CASS foundation and Stafford Fox Medical Research Foundation. Alice P{\'e}bay is an Australian Research Council Future Fellow. Joshua Ho is a National Health and Medical Research Council Career Development Fellow and a National Heart Foundation Future Leader Fellow. The O{\textquoteright}Brien Institute Department, St Vincent{\textquoteright}s Institute of Medical Research, and the Centre for Eye Research Australia receive Operational Infrastructure Support from the Victorian State Government{\textquoteright}s Department of Innovation, Industry and Regional Development. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41598-018-19855-4",

language = "English",

volume = "8",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Nie, S, Wang, X, Sivakumaran, P, Chong, MMW, Liu, X, Karnezis, T, Bandara, N, Takov, K, Nowell, CJ, Wilcox, S, Shambrook, M, Hill, AF, Harris, NC, Newcomb, AE, Strappe, P, Shayan, R, Hernández, D, Clarke, J, Hanssen, E, Davidson, SM, Dusting, GJ, Pébay, A, Ho, JWK, Williamson, N & Lim, SY 2018, 'Biologically active constituents of the secretome of human W8B2⁺ cardiac stem cells', Scientific Reports, vol. 8, no. 1, 1579. https://doi.org/10.1038/s41598-018-19855-4

TY - JOUR

T1 - Biologically active constituents of the secretome of human W8B2+ cardiac stem cells

AU - Nie, Shuai

AU - Wang, Xin

AU - Sivakumaran, Priyadharshini

AU - Chong, Mark M.W.

AU - Liu, Xin

AU - Karnezis, Tara

AU - Bandara, Nadeeka

AU - Takov, Kaloyan

AU - Nowell, Cameron J.

AU - Wilcox, Stephen

AU - Shambrook, Mitch

AU - Hill, Andrew F.

AU - Harris, Nicole C.

AU - Newcomb, Andrew E.

AU - Strappe, Padraig

AU - Shayan, Ramin

AU - Hernández, Damián

AU - Clarke, Jordan

AU - Hanssen, Eric

AU - Davidson, Sean M.

AU - Dusting, Gregory J.

AU - Pébay, Alice

AU - Ho, Joshua W.K.

AU - Williamson, Nicholas

AU - Lim, Shiang Y.

N1 - Funding Information: This work was carried out with support from the St Vincent’s Hospital (Melbourne) Research Endowment Fund, CASS foundation and Stafford Fox Medical Research Foundation. Alice Pébay is an Australian Research Council Future Fellow. Joshua Ho is a National Health and Medical Research Council Career Development Fellow and a National Heart Foundation Future Leader Fellow. The O’Brien Institute Department, St Vincent’s Institute of Medical Research, and the Centre for Eye Research Australia receive Operational Infrastructure Support from the Victorian State Government’s Department of Innovation, Industry and Regional Development. Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41598-018-19855-4

DO - 10.1038/s41598-018-19855-4

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VL - 8

JO - Scientific Reports

JF - Scientific Reports

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ER -

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

Abstract

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