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Enhancing Cartilage Repair Strategies with ROR2

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Review of “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” from STEM CELLS by Stuart P. Atkinson

Mesenchymal stem cells (MSCs) hold great potential in regenerative medicine; however, problems arise from their heterogeneous nature, with distinct cells exhibiting varying bone, fat, and cartilage differentiation propensities. Now, a study from Anthony P. Hollander (University of Liverpool, UK) cuts through this heterogeneity by identifying MSCs with enhanced chondrogenic (cartilage-forming) capacity via the identification of a functional phenotypic marker [1]. 

In a new STEM CELLS study, Dickinson et al. demonstrate that MSCs expressing “inducible receptor tyrosine kinase-like orphan receptor 2” (or ROR2) produce higher amounts levels of high-quality cartilage tissues following transplantation in a large animal model [2]. Is this the key to improved cartilage repair strategies in vivo?

The authors initially cultivated a large number of bone marrow-derived MSC clonal lines under conditions known to maintain chondrogenic differentiation potential. Four selected MSC clones generated cartilage with high dry weight, proteoglycan content, and collagen II/I ratio and subsequent analyses linked these encouraging characteristics to elevated levels of ROR2 mRNA and protein. Further in vitro analyses of uncloned cells confirmed that ROR2-overexpressing MSCs displayed higher chondrogenic capacity when compared to unsorted MSCs or ROR2-negative MSCs.

To test the in vivo function of ROR2-overexpressing MSCs, the authors implanted a “Cell Bandage” [3, 4] composed of cells seeded on a collagen sponge into cartilage defect sites in a sheep model. At three months, cell bandages containing ROR2-overexpressing MSCs formed a greater abundance of repair tissue when compared to control MSCs, although both cell types led to the same quality of cartilage formation as measured biochemically (See Figure).

These findings may lead to the construction of well-defined and efficient MSC-based therapies for cartilage repair in humans; can we also apply a similar strategy to discover functional phenotypic markers that will permit enhanced bone repair? Stay tuned to the Stem Cells Portal to find out!

References

  1. Wakitani S, Okabe T, Horibe S, et al., Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med 2011;5:146-50.
  2. Dickinson SC, Sutton CA, Brady K, et al., 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. STEM CELLS 2017;35:2280-2291.
  3. Pabbruwe MB, Esfandiari E, Kafienah W, et al., Induction of cartilage integration by a chondrocyte/collagen-scaffold implant. Biomaterials 2009;30:4277-86.
  4. Pabbruwe MB, Kafienah W, Tarlton JF, et al., Repair of meniscal cartilage white zone tears using a stem cell/collagen-scaffold implant. Biomaterials 2010;31:2583-91.