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C-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway

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C-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway. / Campagnolo, Paola; Tsai, Tsung Neng; Hong, Xuechong; Kirton, John Paul; So, Po Wah; Margariti, Andriana; Di Bernardini, Elisabetta; Wong, Mei Mei; Hu, Yanhua; Stevens, Molly M.; Xu, Qingbo.

In: Biomaterials, Vol. 60, 01.08.2015, p. 53-61.

Research output: Contribution to journalArticle

Harvard

Campagnolo, P, Tsai, TN, Hong, X, Kirton, JP, So, PW, Margariti, A, Di Bernardini, E, Wong, MM, Hu, Y, Stevens, MM & Xu, Q 2015, 'C-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway', Biomaterials, vol. 60, pp. 53-61. https://doi.org/10.1016/j.biomaterials.2015.04.055

APA

Campagnolo, P., Tsai, T. N., Hong, X., Kirton, J. P., So, P. W., Margariti, A., ... Xu, Q. (2015). C-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway. Biomaterials, 60, 53-61. https://doi.org/10.1016/j.biomaterials.2015.04.055

Vancouver

Campagnolo P, Tsai TN, Hong X, Kirton JP, So PW, Margariti A et al. C-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway. Biomaterials. 2015 Aug 1;60:53-61. https://doi.org/10.1016/j.biomaterials.2015.04.055

Author

Campagnolo, Paola ; Tsai, Tsung Neng ; Hong, Xuechong ; Kirton, John Paul ; So, Po Wah ; Margariti, Andriana ; Di Bernardini, Elisabetta ; Wong, Mei Mei ; Hu, Yanhua ; Stevens, Molly M. ; Xu, Qingbo. / C-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway. In: Biomaterials. 2015 ; Vol. 60. pp. 53-61.

Bibtex Download

@article{fc3ab8ef486b4de299fe6d498c86a718,
title = "C-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway",
abstract = "The development of decellularised scaffolds for small diameter vascular grafts is hampered by their limited patency, due to the lack of luminal cell coverage by endothelial cells (EC) and to the low tone of the vessel due to absence of a contractile smooth muscle cells (SMC). In this study, we identify a population of vascular progenitor c-Kit+/Sca-1- cells available in large numbers and derived from immuno-privileged embryonic stem cells (ESCs). We also define an efficient and controlled differentiation protocol yielding fully to differentiated ECs and SMCs in sufficient numbers to allow the repopulation of a tissue engineered vascular graft. When seeded exvivo on a decellularised vessel, c-Kit+/Sca-1-derived cells recapitulated the native vessel structure and upon invivo implantation in the mouse, markedly reduced neointima formation and mortality, restoring functional vascularisation. We showed that Kr{\"u}ppel-like transcription factor 4 (Klf4) regulates the choice of differentiation pathway of these cells through β-catenin activation and was itself regulated by the canonical Wnt pathway activator lithium chloride. Our data show that ESC-derived c-Kit+/Sca-1-cells can be differentiated through a Klf4/β-catenin dependent pathway and are a suitable source of vascular progenitors for the creation of superior tissue-engineered vessels from decellularised scaffolds.",
keywords = "Cell signalling, Endothelialization, Stem cells, Vascular graft",
author = "Paola Campagnolo and Tsai, {Tsung Neng} and Xuechong Hong and Kirton, {John Paul} and So, {Po Wah} and Andriana Margariti and {Di Bernardini}, Elisabetta and Wong, {Mei Mei} and Yanhua Hu and Stevens, {Molly M.} and Qingbo Xu",
year = "2015",
month = "8",
day = "1",
doi = "10.1016/j.biomaterials.2015.04.055",
language = "English",
volume = "60",
pages = "53--61",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - C-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway

AU - Campagnolo, Paola

AU - Tsai, Tsung Neng

AU - Hong, Xuechong

AU - Kirton, John Paul

AU - So, Po Wah

AU - Margariti, Andriana

AU - Di Bernardini, Elisabetta

AU - Wong, Mei Mei

AU - Hu, Yanhua

AU - Stevens, Molly M.

AU - Xu, Qingbo

PY - 2015/8/1

Y1 - 2015/8/1

N2 - The development of decellularised scaffolds for small diameter vascular grafts is hampered by their limited patency, due to the lack of luminal cell coverage by endothelial cells (EC) and to the low tone of the vessel due to absence of a contractile smooth muscle cells (SMC). In this study, we identify a population of vascular progenitor c-Kit+/Sca-1- cells available in large numbers and derived from immuno-privileged embryonic stem cells (ESCs). We also define an efficient and controlled differentiation protocol yielding fully to differentiated ECs and SMCs in sufficient numbers to allow the repopulation of a tissue engineered vascular graft. When seeded exvivo on a decellularised vessel, c-Kit+/Sca-1-derived cells recapitulated the native vessel structure and upon invivo implantation in the mouse, markedly reduced neointima formation and mortality, restoring functional vascularisation. We showed that Krüppel-like transcription factor 4 (Klf4) regulates the choice of differentiation pathway of these cells through β-catenin activation and was itself regulated by the canonical Wnt pathway activator lithium chloride. Our data show that ESC-derived c-Kit+/Sca-1-cells can be differentiated through a Klf4/β-catenin dependent pathway and are a suitable source of vascular progenitors for the creation of superior tissue-engineered vessels from decellularised scaffolds.

AB - The development of decellularised scaffolds for small diameter vascular grafts is hampered by their limited patency, due to the lack of luminal cell coverage by endothelial cells (EC) and to the low tone of the vessel due to absence of a contractile smooth muscle cells (SMC). In this study, we identify a population of vascular progenitor c-Kit+/Sca-1- cells available in large numbers and derived from immuno-privileged embryonic stem cells (ESCs). We also define an efficient and controlled differentiation protocol yielding fully to differentiated ECs and SMCs in sufficient numbers to allow the repopulation of a tissue engineered vascular graft. When seeded exvivo on a decellularised vessel, c-Kit+/Sca-1-derived cells recapitulated the native vessel structure and upon invivo implantation in the mouse, markedly reduced neointima formation and mortality, restoring functional vascularisation. We showed that Krüppel-like transcription factor 4 (Klf4) regulates the choice of differentiation pathway of these cells through β-catenin activation and was itself regulated by the canonical Wnt pathway activator lithium chloride. Our data show that ESC-derived c-Kit+/Sca-1-cells can be differentiated through a Klf4/β-catenin dependent pathway and are a suitable source of vascular progenitors for the creation of superior tissue-engineered vessels from decellularised scaffolds.

KW - Cell signalling

KW - Endothelialization

KW - Stem cells

KW - Vascular graft

UR - http://www.scopus.com/inward/record.url?scp=84930442389&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2015.04.055

DO - 10.1016/j.biomaterials.2015.04.055

M3 - Article

AN - SCOPUS:84930442389

VL - 60

SP - 53

EP - 61

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -

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