Cardiosphere Derived Cells Require Endoglin For Paracrine-Mediated Angiogenesis

Rachael E Redgrave; Simon Tual-Chalot; Benjamin Davidson; Esha Singh; Darroch Hall; Muhammad M Amirrasouli; Derek Gilchrist; Alexander Medvinsky; Helen M Arthur

doi:10.1016/j.stemcr.2017.04.015

Cardiosphere Derived Cells Require Endoglin For Paracrine-Mediated Angiogenesis

Rachael E Redgrave, Simon Tual-Chalot, Benjamin Davidson, Esha Singh, Darroch Hall, Muhammad M Amirrasouli, Derek Gilchrist, Alexander Medvinsky, Helen M Arthur

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

Abstract / Description of output

Clinical trials of stem cell therapy to treat ischaemic heart disease primarily use heterogeneous stem cell populations. Small benefits occur via paracrine mechanisms that include stimulating angiogenesis and increased understanding of these mechanisms would help to improve patient outcomes. Cardiosphere-derived-cells (CDCs) are an example of these heterogeneous stem cell populations, cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds specific TGFβ family ligands, including BMP9. In endothelial cells, endoglin regulates angiogenic responses and we therefore hypothesised endoglin is required to promote the paracrine proangiogenic properties of CDCs. Cre/LoxP technology was used to genetically manipulate endoglin expression in CDCs and we found the pro-angiogenic properties of the CDC secretome are endoglin-dependent both in vitro and in vivo. Importantly, BMP9 pre-treatment of endoglin-depleted CDCs restores their pro-angiogenic paracrine properties. As BMP9 signalling is normally required to maintain endoglin expression, we propose media containing BMP9 could be critical for therapeutic CDC preparation.

Original language	English
Pages (from-to)	1287-1298
Number of pages	12
Journal	Stem Cell Reports
Volume	8
Issue number	5
Early online date	9 May 2017
DOIs	https://doi.org/10.1016/j.stemcr.2017.04.015 https://doi.org/10.1016/j.stemcr.2017.04.015
Publication status	Published - 9 May 2017

Keywords / Materials (for Non-textual outputs)

Angiogenesis
CD105
MSC
TGF-beta
ischemic disease
BMP9

Access to Document

PIIS2213671117301698Final published version, 2.49 MBLicence: CC BY
1-s2.0-S2213671117301698-main
StemCellReports Vol. 8 1287–1298 May 9, 2017 2017 The Author(s). 1287 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 2.4 MBLicence: CC BY

Cite this

Redgrave, R. E., Tual-Chalot, S., Davidson, B., Singh, E., Hall, D., Amirrasouli, M. M., Gilchrist, D., Medvinsky, A., & Arthur, H. M. (2017). Cardiosphere Derived Cells Require Endoglin For Paracrine-Mediated Angiogenesis. Stem Cell Reports, 8(5), 1287-1298. Advance online publication. https://doi.org/10.1016/j.stemcr.2017.04.015, https://doi.org/10.1016/j.stemcr.2017.04.015

@article{69eb989d8bfa4c8dbbd7c53a1d312f6d,

title = "Cardiosphere Derived Cells Require Endoglin For Paracrine-Mediated Angiogenesis",

abstract = "Clinical trials of stem cell therapy to treat ischaemic heart disease primarily use heterogeneous stem cell populations. Small benefits occur via paracrine mechanisms that include stimulating angiogenesis and increased understanding of these mechanisms would help to improve patient outcomes. Cardiosphere-derived-cells (CDCs) are an example of these heterogeneous stem cell populations, cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds specific TGFβ family ligands, including BMP9. In endothelial cells, endoglin regulates angiogenic responses and we therefore hypothesised endoglin is required to promote the paracrine proangiogenic properties of CDCs. Cre/LoxP technology was used to genetically manipulate endoglin expression in CDCs and we found the pro-angiogenic properties of the CDC secretome are endoglin-dependent both in vitro and in vivo. Importantly, BMP9 pre-treatment of endoglin-depleted CDCs restores their pro-angiogenic paracrine properties. As BMP9 signalling is normally required to maintain endoglin expression, we propose media containing BMP9 could be critical for therapeutic CDC preparation.",

keywords = "Angiogenesis , CD105, MSC, TGF-beta, ischemic disease, BMP9",

author = "Redgrave, {Rachael E} and Simon Tual-Chalot and Benjamin Davidson and Esha Singh and Darroch Hall and Amirrasouli, {Muhammad M} and Derek Gilchrist and Alexander Medvinsky and Arthur, {Helen M}",

note = "This research was funded by program grant RG/12/2/29416 from the British Heart Foundation. S.T.-C. was supported by VASC-GEN, an Intra-European Fellowship from the European Commission, and B.J.D. was supported by a clinical training fellowship from the British Heart Foundation (FS/09/027/27871).",

year = "2017",

month = may,

day = "9",

doi = "10.1016/j.stemcr.2017.04.015",

language = "English",

volume = "8",

pages = "1287--1298",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Cardiosphere Derived Cells Require Endoglin For Paracrine-Mediated Angiogenesis

AU - Redgrave, Rachael E

AU - Tual-Chalot, Simon

AU - Davidson, Benjamin

AU - Singh, Esha

AU - Hall, Darroch

AU - Amirrasouli, Muhammad M

AU - Gilchrist, Derek

AU - Medvinsky, Alexander

AU - Arthur, Helen M

N1 - This research was funded by program grant RG/12/2/29416 from the British Heart Foundation. S.T.-C. was supported by VASC-GEN, an Intra-European Fellowship from the European Commission, and B.J.D. was supported by a clinical training fellowship from the British Heart Foundation (FS/09/027/27871).

PY - 2017/5/9

Y1 - 2017/5/9

N2 - Clinical trials of stem cell therapy to treat ischaemic heart disease primarily use heterogeneous stem cell populations. Small benefits occur via paracrine mechanisms that include stimulating angiogenesis and increased understanding of these mechanisms would help to improve patient outcomes. Cardiosphere-derived-cells (CDCs) are an example of these heterogeneous stem cell populations, cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds specific TGFβ family ligands, including BMP9. In endothelial cells, endoglin regulates angiogenic responses and we therefore hypothesised endoglin is required to promote the paracrine proangiogenic properties of CDCs. Cre/LoxP technology was used to genetically manipulate endoglin expression in CDCs and we found the pro-angiogenic properties of the CDC secretome are endoglin-dependent both in vitro and in vivo. Importantly, BMP9 pre-treatment of endoglin-depleted CDCs restores their pro-angiogenic paracrine properties. As BMP9 signalling is normally required to maintain endoglin expression, we propose media containing BMP9 could be critical for therapeutic CDC preparation.

AB - Clinical trials of stem cell therapy to treat ischaemic heart disease primarily use heterogeneous stem cell populations. Small benefits occur via paracrine mechanisms that include stimulating angiogenesis and increased understanding of these mechanisms would help to improve patient outcomes. Cardiosphere-derived-cells (CDCs) are an example of these heterogeneous stem cell populations, cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds specific TGFβ family ligands, including BMP9. In endothelial cells, endoglin regulates angiogenic responses and we therefore hypothesised endoglin is required to promote the paracrine proangiogenic properties of CDCs. Cre/LoxP technology was used to genetically manipulate endoglin expression in CDCs and we found the pro-angiogenic properties of the CDC secretome are endoglin-dependent both in vitro and in vivo. Importantly, BMP9 pre-treatment of endoglin-depleted CDCs restores their pro-angiogenic paracrine properties. As BMP9 signalling is normally required to maintain endoglin expression, we propose media containing BMP9 could be critical for therapeutic CDC preparation.

KW - Angiogenesis

KW - CD105

KW - MSC

KW - TGF-beta

KW - ischemic disease

KW - BMP9

UR - http://www.scopus.com/inward/record.url?scp=85019484120&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2017.04.015

DO - 10.1016/j.stemcr.2017.04.015

M3 - Article

AN - SCOPUS:85019484120

SN - 2213-6711

VL - 8

SP - 1287

EP - 1298

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 5

ER -

Cardiosphere Derived Cells Require Endoglin For Paracrine-Mediated Angiogenesis

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Other files and links

Fingerprint

Cite this