Vasculogenic properties of adventitial Sca-1 + CD45 + progenitor cells in mice

a potential source of vasa vasorum in atherosclerosis

Deborah Toledo-Flores, Anna Williamson, Nisha Schwarz, Sanuja Fernando, Catherine Dimasi, Tyra A. Witt, Thao M. Nguyen, Amrutesh S. Puranik, Colin D. Chue, Sinny Delacroix, Daniel B. Spoon, Claudine S. Bonder, Christina A. Bursill, Belinda A. Di Bartolo, Stephen J. Nicholls, Robert D. Simari, Peter J. Psaltis

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1 + CD45 + progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1 + CD45 + cells were localised to adventitia and lacked surface expression of endothelial markers (<1% for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE −/− aortas. Although Sca-1 + CD45 + cells from C57BL/6 aorta did not express CD31, they formed CD31 + colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1 + CD45 + cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE −/− mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1 + CD45 + cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.

Original languageEnglish
Article number7286
Number of pages15
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019
Externally publishedYes

Cite this

Toledo-Flores, D., Williamson, A., Schwarz, N., Fernando, S., Dimasi, C., Witt, T. A., ... Psaltis, P. J. (2019). Vasculogenic properties of adventitial Sca-1 + CD45 + progenitor cells in mice: a potential source of vasa vasorum in atherosclerosis. Scientific Reports, 9(1), [7286]. https://doi.org/10.1038/s41598-019-43765-8
Toledo-Flores, Deborah ; Williamson, Anna ; Schwarz, Nisha ; Fernando, Sanuja ; Dimasi, Catherine ; Witt, Tyra A. ; Nguyen, Thao M. ; Puranik, Amrutesh S. ; Chue, Colin D. ; Delacroix, Sinny ; Spoon, Daniel B. ; Bonder, Claudine S. ; Bursill, Christina A. ; Di Bartolo, Belinda A. ; Nicholls, Stephen J. ; Simari, Robert D. ; Psaltis, Peter J. / Vasculogenic properties of adventitial Sca-1 + CD45 + progenitor cells in mice : a potential source of vasa vasorum in atherosclerosis. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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title = "Vasculogenic properties of adventitial Sca-1 + CD45 + progenitor cells in mice: a potential source of vasa vasorum in atherosclerosis",
abstract = "The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1 + CD45 + progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1 + CD45 + cells were localised to adventitia and lacked surface expression of endothelial markers (<1{\%} for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE −/− aortas. Although Sca-1 + CD45 + cells from C57BL/6 aorta did not express CD31, they formed CD31 + colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1 + CD45 + cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50{\%} increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE −/− mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1 + CD45 + cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.",
author = "Deborah Toledo-Flores and Anna Williamson and Nisha Schwarz and Sanuja Fernando and Catherine Dimasi and Witt, {Tyra A.} and Nguyen, {Thao M.} and Puranik, {Amrutesh S.} and Chue, {Colin D.} and Sinny Delacroix and Spoon, {Daniel B.} and Bonder, {Claudine S.} and Bursill, {Christina A.} and {Di Bartolo}, {Belinda A.} and Nicholls, {Stephen J.} and Simari, {Robert D.} and Psaltis, {Peter J.}",
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Toledo-Flores, D, Williamson, A, Schwarz, N, Fernando, S, Dimasi, C, Witt, TA, Nguyen, TM, Puranik, AS, Chue, CD, Delacroix, S, Spoon, DB, Bonder, CS, Bursill, CA, Di Bartolo, BA, Nicholls, SJ, Simari, RD & Psaltis, PJ 2019, 'Vasculogenic properties of adventitial Sca-1 + CD45 + progenitor cells in mice: a potential source of vasa vasorum in atherosclerosis', Scientific Reports, vol. 9, no. 1, 7286. https://doi.org/10.1038/s41598-019-43765-8

Vasculogenic properties of adventitial Sca-1 + CD45 + progenitor cells in mice : a potential source of vasa vasorum in atherosclerosis. / Toledo-Flores, Deborah; Williamson, Anna; Schwarz, Nisha; Fernando, Sanuja; Dimasi, Catherine; Witt, Tyra A.; Nguyen, Thao M.; Puranik, Amrutesh S.; Chue, Colin D.; Delacroix, Sinny; Spoon, Daniel B.; Bonder, Claudine S.; Bursill, Christina A.; Di Bartolo, Belinda A.; Nicholls, Stephen J.; Simari, Robert D.; Psaltis, Peter J.

In: Scientific Reports, Vol. 9, No. 1, 7286, 01.12.2019.

Research output: Contribution to journalArticleResearchpeer-review

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T2 - a potential source of vasa vasorum in atherosclerosis

AU - Toledo-Flores, Deborah

AU - Williamson, Anna

AU - Schwarz, Nisha

AU - Fernando, Sanuja

AU - Dimasi, Catherine

AU - Witt, Tyra A.

AU - Nguyen, Thao M.

AU - Puranik, Amrutesh S.

AU - Chue, Colin D.

AU - Delacroix, Sinny

AU - Spoon, Daniel B.

AU - Bonder, Claudine S.

AU - Bursill, Christina A.

AU - Di Bartolo, Belinda A.

AU - Nicholls, Stephen J.

AU - Simari, Robert D.

AU - Psaltis, Peter J.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1 + CD45 + progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1 + CD45 + cells were localised to adventitia and lacked surface expression of endothelial markers (<1% for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE −/− aortas. Although Sca-1 + CD45 + cells from C57BL/6 aorta did not express CD31, they formed CD31 + colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1 + CD45 + cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE −/− mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1 + CD45 + cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.

AB - The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1 + CD45 + progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1 + CD45 + cells were localised to adventitia and lacked surface expression of endothelial markers (<1% for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE −/− aortas. Although Sca-1 + CD45 + cells from C57BL/6 aorta did not express CD31, they formed CD31 + colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1 + CD45 + cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE −/− mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1 + CD45 + cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.

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