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Re-Differentiation of Human Meniscus Fibrochondrocytes Differs in Three-Dimensional Cell Aggregates and Decellularized Human Meniscus Matrix Scaffolds

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Abstract

Decellularized matrix (DCM) derived from native tissues may be a promising supporting material to induce cellular differentiation by sequestered bioactive factors. However, no previous study has investigated the use of human meniscus-derived DCM to re-differentiate human meniscus fibrochondrocytes (MFCs) to form meniscus-like extracellular matrix (ECM). We expanded human MFCs and seeded them upon a cadaveric meniscus-derived DCM prepared by physical homogenization under hypoxia. To assess the bioactivity of the DCM, we used conditions with and without chondrogenic factor TGF-β3 and set up a cell pellet culture model as a biomaterial-free control. We found that the DCM supported chondrogenic re-differentiation and ECM formation of MFCs only in the presence of exogenous TGF-β3. Chondrogenic re-differentiation was more robust at the protein level in the pellet model as MFCs on the DCM appeared to favour a more proliferative phenotype. Interestingly, without growth factors, the DCM tended to promote expression of hypertrophic differentiation markers relative to the pellet model. Therefore, the human meniscus-derived DCM prepared by physical homogenization contained insufficient bioactive factors to induce appreciable ECM formation by human MFCs.

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Acknowledgments

Financial support was provided by Canadian Institutes for Health Research (CIHR MOP 125921), Canadian Foundation for Innovation (CFI 33786), University Hospital Foundation (RES0028185), Natural Sciences and Engineering Research Council (NSERC RGPIN-2018-06290) to AA. Stipend support to YL was provided by Li Ka Shing Foundation. We thank the Comprehensive Tissue Centre, Alberta Health Services for acquisition and donation of human cadaver tissue specimens. We thank Dr. Jian Ling (Southwest Research Institute, San Antonio, Texas, USA) for performing ethylene oxide sterilization. We thank the Uludag Lab at the University of Alberta for assistance with freeze drying. We thank the Mr. Woo Jung Cho (Faculty of Medicine and Dentistry, Cell Imaging Center, University of Alberta, Alberta, Canada) for SEM analysis.

Author information

YL conducted the experiments and was responsible for data acquisition, analysis, and bulk of manuscript writing. AS was involved in data analysis and manuscript writing. EI, MK and AMS were involved in immunofluorescence, gene expression analysis, and cell culture. ABA conceived the study, supervised the study, performed data analysis, manuscript writing, and was responsible for final review of the manuscript. All authors read and approved the final manuscript.

Correspondence to Adetola B. Adesida.

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Liang, Y., Szojka, A.R.A., Idrees, E. et al. Re-Differentiation of Human Meniscus Fibrochondrocytes Differs in Three-Dimensional Cell Aggregates and Decellularized Human Meniscus Matrix Scaffolds. Ann Biomed Eng 48, 968–979 (2020). https://doi.org/10.1007/s10439-019-02272-7

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Keywords

  • Meniscus fibrochondrocytes
  • Tissue engineering
  • Differentiation
  • Extracellular matrix