Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells

Agneta Månsson-Broberg; Sergey Rodin; Ivana Bulatovic; Cristián Ibarra; Marie Löfling; Rami Genead; Eva Wärdell; Ulrika Felldin; Carl Granath; Evren Alici; Katarina Le Blanc; C. I.Edvard Smith; Alena Salašová; Magnus Westgren; Erik Sundström; Per Uhlén; Ernest Arenas; Christer Sylvén; Karl Tryggvason; Matthias Corbascio; Oscar E. Simonson; Cecilia Österholm; Karl Henrik Grinnemo

doi:10.1016/j.stemcr.2016.02.014

Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells

Agneta Månsson-Broberg, Sergey Rodin, Ivana Bulatovic, Cristián Ibarra, Marie Löfling, Rami Genead, Eva Wärdell, Ulrika Felldin, Carl Granath, Evren Alici, Katarina Le Blanc, C. I.Edvard Smith, Alena Salašová, Magnus Westgren, Erik Sundström, Per Uhlén, Ernest Arenas, Christer Sylvén, Karl Tryggvason, Matthias CorbascioOscar E. Simonson, Cecilia Österholm, Karl Henrik Grinnemo^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

16 Citations (Scopus)

Abstract

The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN)-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.

Original language	English
Journal	Stem Cell Reports
Volume	6
Issue	4
Pages (from-to)	607-617
Number of pages	11
ISSN	2213-6711
DOIs	https://doi.org/10.1016/j.stemcr.2016.02.014
Publication status	Published - 12 Apr 2016
Externally published	Yes

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Månsson-Broberg, A., Rodin, S., Bulatovic, I., Ibarra, C., Löfling, M., Genead, R., Wärdell, E., Felldin, U., Granath, C., Alici, E., Le Blanc, K., Smith, C. I. E., Salašová, A., Westgren, M., Sundström, E., Uhlén, P., Arenas, E., Sylvén, C., Tryggvason, K., ... Grinnemo, K. H. (2016). Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells. Stem Cell Reports, 6(4), 607-617. https://doi.org/10.1016/j.stemcr.2016.02.014

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title = "Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells",

abstract = "The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN)-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.",

author = "Agneta M{\aa}nsson-Broberg and Sergey Rodin and Ivana Bulatovic and Cristi{\'a}n Ibarra and Marie L{\"o}fling and Rami Genead and Eva W{\"a}rdell and Ulrika Felldin and Carl Granath and Evren Alici and {Le Blanc}, Katarina and Smith, {C. I.Edvard} and Alena Sala{\v s}ov{\'a} and Magnus Westgren and Erik Sundstr{\"o}m and Per Uhl{\'e}n and Ernest Arenas and Christer Sylv{\'e}n and Karl Tryggvason and Matthias Corbascio and Simonson, {Oscar E.} and Cecilia {\"O}sterholm and Grinnemo, {Karl Henrik}",

note = "Publisher Copyright: {\textcopyright} 2016 The Authors.",

year = "2016",

month = apr,

day = "12",

doi = "10.1016/j.stemcr.2016.02.014",

language = "English",

volume = "6",

pages = "607--617",

journal = "Stem Cell Reports",

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Månsson-Broberg, A, Rodin, S, Bulatovic, I, Ibarra, C, Löfling, M, Genead, R, Wärdell, E, Felldin, U, Granath, C, Alici, E, Le Blanc, K, Smith, CIE, Salašová, A, Westgren, M, Sundström, E, Uhlén, P, Arenas, E, Sylvén, C, Tryggvason, K, Corbascio, M, Simonson, OE, Österholm, C & Grinnemo, KH 2016, 'Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells', Stem Cell Reports, vol. 6, no. 4, pp. 607-617. https://doi.org/10.1016/j.stemcr.2016.02.014

Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells. / Månsson-Broberg, Agneta; Rodin, Sergey; Bulatovic, Ivana et al.
In: Stem Cell Reports, Vol. 6, No. 4, 12.04.2016, p. 607-617.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells

AU - Månsson-Broberg, Agneta

AU - Rodin, Sergey

AU - Bulatovic, Ivana

AU - Ibarra, Cristián

AU - Löfling, Marie

AU - Genead, Rami

AU - Wärdell, Eva

AU - Felldin, Ulrika

AU - Granath, Carl

AU - Alici, Evren

AU - Le Blanc, Katarina

AU - Smith, C. I.Edvard

AU - Salašová, Alena

AU - Westgren, Magnus

AU - Sundström, Erik

AU - Uhlén, Per

AU - Arenas, Ernest

AU - Sylvén, Christer

AU - Tryggvason, Karl

AU - Corbascio, Matthias

AU - Simonson, Oscar E.

AU - Österholm, Cecilia

AU - Grinnemo, Karl Henrik

PY - 2016/4/12

Y1 - 2016/4/12

N2 - The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN)-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.

AB - The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN)-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.

UR - http://www.scopus.com/inward/record.url?scp=84963650421&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2016.02.014

DO - 10.1016/j.stemcr.2016.02.014

M3 - Journal article

C2 - 27052314

AN - SCOPUS:84963650421

SN - 2213-6711

VL - 6

SP - 607

EP - 617

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 4

ER -

Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells

Abstract

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