The Wnt5a Receptor, Receptor Tyrosine Kinase‐Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation

The Wnt5a Receptor, Receptor Tyrosine Kinase‐Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation

Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However, until now, their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue f...

Full description

Saved in:
Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Vol. 35; no. 11; pp. 2280 - 2291
Main Authors: Dickinson, Sally C., Sutton, Catherine A., Brady, Kyla, Salerno, Anna, Katopodi, Theoni, Williams, Rhys L., West, Christopher C., Evseenko, Denis, Wu, Ling, Pang, Suzanna, Ferro de Godoy, Roberta, Goodship, Allen E., Péault, Bruno, Blom, Ashley W., Kafienah, Wael, Hollander, Anthony P.
Format: Journal Article
Language:English
Published: United States Oxford University Press 01-11-2017
John Wiley and Sons Inc
Subjects:
Adipose tissue
Animals
Arthritis
Biocompatibility
Biomedical materials
Bone marrow
Cartilage
Cartilage diseases
Cell Differentiation
Cell Proliferation
Cell Signaling
Cell surface
Cell Surface Markers
Cells, Cultured
Cellular therapy
Chondrogenesis
Chondrogenesis - genetics
Differentiation
Humans
Mesenchymal Stem Cells
Mesenchymal Stem Cells - metabolism
Mesenchyme
Osteoarthritis
Patients
Populations
Protein-tyrosine kinase receptors
Receptor Tyrosine Kinase-like Orphan Receptors - genetics
Receptor Tyrosine Kinase-like Orphan Receptors - metabolism
Regenerative medicine
Sheep
Stem cells
Surface markers
Tissue Engineering
Tissue‐Specific Stem Cells
Tyrosine
Wnt protein
Wnt-5a Protein - genetics
Wnt-5a Protein - metabolism
Cell Signaling
Arthritis
Tissue engineering
Cellular therapy
Mesenchymal stem cells
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However, until now, their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue formation. Here, we identify receptor tyrosine kinase‐like orphan receptor 2 (ROR2) as a cell surface marker expressed by those MSCs with an enhanced capacity for cartilage formation. We generated clonal human MSC populations with varying capacities for chondrogenesis. ROR2 was identified through screening for upregulated genes in the most chondrogenic clones. When isolated from uncloned populations, ROR2+ve MSCs were significantly more chondrogenic than either ROR2–ve or unfractionated MSCs. In a sheep cartilage‐repair model, they produced significantly more defect filling with no loss of cartilage quality compared with controls. ROR2+ve MSCs/perivascular cells were present in developing human cartilage, adult bone marrow, and adipose tissue. Their frequency in bone marrow was significantly lower in patients with osteoarthritis (OA) than in controls. However, after isolation of these cells and their initial expansion in vitro, there was greater ROR2 expression in the population derived from OA patients compared with controls. Furthermore, osteoarthritis‐derived MSCs were better able to form cartilage than MSCs from control patients in a tissue engineering assay. We conclude that MSCs expressing high levels of ROR2 provide a defined population capable of predictably enhanced cartilage production. Stem Cells 2017;35:2280–2291 The in vivo and ex vivo origin of ROR2+ve cells in human tissues. Immunolocalization of ROR2, in comparison to the pericyte marker CD146, in the developing ulna limb bud from a human fetus of 11‐12 weeks gestation. Regions of bone marrow stroma and blood vessels are shown. ROR2 expression was also analyzed by cell sorting in samples of fresh, uncultured adult human bone marrow and adipose tissue to determine the proportion of cells expressing ROR2 on initial isolation.
Bibliography:Deceased.
The copyright line for this article was changed on 28 November 2017 after original online publication
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.2691