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

Sally Dickinson, Catherine Sutton, Kyla Brady, Anna Salerno, Theoni Katopodi, Rhys Williams, Christopher West, Denis Evseenko, Ling Wu, Suzanna Pang, Roberta Ferro de Godoy, Allen Goodship, Bruno Peault, Ashley Blom, Wael Kafienah, Anthony Hollander

Research output: Contribution to journalArticle (Academic Journal)peer-review

33 Citations (Scopus)
267 Downloads (Pure)

Abstract

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 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 un-cloned 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 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 osteoarthritis 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
Original languageEnglish
Number of pages13
JournalStem Cells
Volume35
Issue number11
Early online date30 Aug 2017
DOIs
Publication statusE-pub ahead of print - 30 Aug 2017

Structured keywords

  • Centre for Surgical Research

Keywords

  • Mesenchymal stem cells
  • TISSUE ENGINEERING
  • ARTHRITIS
  • Cellular therapy
  • Cell Signaling

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