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Stem Cell Reports. 2016 Apr 12;6(4):607-617. doi: 10.1016/j.stemcr.2016.02.014. Epub 2016 Mar 24.

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

Author information

1
Division of Cardiology, Department of Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.
2
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
3
Division of Cardiothoracic Surgery and Anesthesiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, 17177 Stockholm, Sweden.
4
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden; Cardiovascular & Metabolic Diseases, Innovative Medicines and Early Development, AstraZeneca R&D, 43150 Mölndal, Sweden.
5
Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 17177 Stockholm, Sweden; Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.
6
Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 17177 Stockholm, Sweden; Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, 17177 Stockholm, Sweden.
7
Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, 17177 Stockholm, Sweden.
8
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
9
CLINTEC, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital, 17177 Stockholm, Sweden.
10
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, 17177 Stockholm, Sweden.
11
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden; Duke-NUS Graduate Medical School, Durham, NC 27710, USA.
12
Division of Cardiothoracic Surgery and Anesthesiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, 17177 Stockholm, Sweden; Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.
13
Division of Cardiothoracic Surgery and Anesthesiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, 17177 Stockholm, Sweden; Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. Electronic address: karl-henrik.grinnemo@karolinska.se.

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.

PMID:
27052314
PMCID:
PMC4834052
DOI:
10.1016/j.stemcr.2016.02.014
[Indexed for MEDLINE]
Free PMC Article

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