Passaged Articular Chondrocytes From the Superficial Zone and Deep Zone Can Regain Zone-Specific Properties After Redifferentiation

Author:

Davis Elizabeth E.R.12,Manzoni Thomas J.3ORCID,Bianchi Vanessa J.12,Weber Joanna F.45,Wu Po Han6,Regmi Suresh C.7,Waldman Stephen D.58,Schmidt Tannin A.9,Su Alvin W.10,Kandel Rita A.121112,Parreno Justin213ORCID

Affiliation:

1. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

2. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada

3. Department of Biological Sciences, University of Delaware, Newark, Delaware, USA

4. Department of Mechanical and Materials Engineering, Queen’s University, Kingston, Ontario, Canada

5. Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario, Canada

6. Department of Human Biology, University of Toronto, Toronto, Ontario, Canada

7. Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada

8. Department of Chemical Engineering, Toronto Metropolitan University, Toronto, Ontario, Canada

9. Biomedical Engineering Department, University of Connecticut Health Center, Farmington, Connecticut, USA

10. Nemours Sports Medicine, Department of Orthopaedic Surgery, Nemours Children’s Hospital, Wilmington, Delaware, USA

11. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

12. Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

13. Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA

Abstract

Background: Bioengineered cartilage is a developing therapeutic to repair cartilage defects. The matrix must be rich in collagen type II and aggrecan and mechanically competent, withstanding compressive and shearing loads. Biomechanical properties in native articular cartilage depend on the zonal architecture consisting of 3 zones: superficial, middle, and deep. The superficial zone chondrocytes produce lubricating proteoglycan-4, whereas the deep zone chondrocytes produce collagen type X, which allows for integration into the subchondral bone. Zonal and chondrogenic expression is lost after cell number expansion. Current cell-based therapies have limited capacity to regenerate the zonal structure of native cartilage. Hypothesis: Both passaged superficial and deep zone chondrocytes at high density can form bioengineered cartilage that is rich in collagen type II and aggrecan; however, only passaged superficial zone–derived chondrocytes will express superficial zone–specific proteoglycan-4, and only passaged deep zone–derived chondrocytes will express deep zone–specific collagen type X. Study Design: Controlled laboratory study. Methods: Superficial and deep zone chondrocytes were isolated from bovine joints, and zonal subpopulations were separately expanded in 2-dimensional culture. At passage 2, superficial and deep zone chondrocytes were seeded, separately, in scaffold-free 3-dimensional culture within agarose wells and cultured in redifferentiation media. Results: Monolayer expansion resulted in loss of expression for proteoglycan-4 and collagen type X in passaged superficial and deep zone chondrocytes, respectively. By passage 2, superficial and deep zone chondrocytes had similar expression for dedifferentiated molecules collagen type I and tenascin C. Redifferentiation of both superficial and deep zone chondrocytes led to the expression of collagen type II and aggrecan in both passaged chondrocyte populations. However, only redifferentiated deep zone chondrocytes expressed collagen type X, and only redifferentiated superficial zone chondrocytes expressed and secreted proteoglycan-4. Additionally, redifferentiated deep zone chondrocytes produced a thicker and more robust tissue compared with superficial zone chondrocytes. Conclusion: The recapitulation of the primary phenotype from passaged zonal chondrocytes introduces a novel method of functional bioengineering of cartilage that resembles the zone-specific biological properties of native cartilage. Clinical Relevance: The recapitulation of the primary phenotype in zonal chondrocytes could be a possible method to tailor bioengineered cartilage to have zone-specific expression.

Funder

american orthopaedic society for sports medicine

Natural Sciences and Engineering Research Council of Canada

National Institute of General Medical Sciences

Publisher

SAGE Publications

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