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Cited by 63Tissue Engineering and Regenerative MedicineOsteoarthritis Treatment and MechanismsHydrogels: synthesis, properties, applications

Extracellular matrix derived from chondrocytes promotes rapid expansion of human primary chondrocytes in vitro with reduced dedifferentiation

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Mao, Yong, Block, Travis, Singh-Varma, Anya, Sheldrake, Anne, Leeth, Rachel, Griffey, Sy, Kohn, Joachim·2019·Acta Biomaterialia
DOI 10.1016/j.actbio.2018.12.006
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Abstract

A significant expansion of autologous chondrocytes in vitro is required for cell-based cartilage repair. However, the in vitro expansion of chondrocytes under standard culture conditions inevitably leads to the dedifferentiation of chondrocytes and contributes to suboptimal clinical outcomes. To address this challenge, we focused our efforts on developing an improved in vitro expansion protocol, which shortens the expansion time with decreased dedifferentiation. It is known that the tissue microenvironment plays a critical role in regulating the cellular functions of resident cells and provides guidance in tissue-specific regeneration. We hypothesized that chondrocyte extracellular matrix (ECM) mimics a native microenvironment and that it may support chondrocyte expansion in vitro. To test this hypothesis, we prepared decellularized ECMs from allogeneic human articular chondrocytes (HAC) (AC-ECM) and bone marrow stromal cells (BM-ECM) and studied their effects on the in vitro expansion of primary HAC. The differential composition and physical properties of these two ECMs were revealed by mass spectrometry and atomic force microscopy. Compared with standard tissue culture polystyrene (TCP) or BM-ECM, HAC cultured on AC-ECM proliferated faster and maintained the highest ratio of COL2A1/COL1A1. Furthermore, a pellet culture study demonstrated that cells expanded on AC-ECM produced a more cartilage-like ECM than cells expanded on BM-ECM or TCP. This is the first report on modulating chondrocyte expansion and dedifferentiation using cell type-specific ECM and on identifying AC-ECM as a preferred substrate for in vitro expansion of HAC cell-based therapies. STATEMENT OF SIGNIFICANCE: To reduce the dedifferentiation of chondrocytes during in vitro expansion, cell type-specific extracellular matrix (ECM), which mimics a native microenvironment, was prepared from human articular chondrocytes (AC-ECM) or bone marrow stromal cells (BM-ECM). As demonstrated by mass spectrometry and atomic force microscopy, AC-ECM and BM-ECM have differential ECM compositions and physical characteristics. Human articular chondrocytes (HAC) expanded faster and maintained a better chondrocyte phenotype on AC-ECM than on BM-ECM or a standard culture surface. AC-ECM has potential to be developed for expanding HAC for cell-based therapies.

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Cited by

Sorted by citations

Authors
Mao, Y., Block, T., Singh-Varma, A., Sheldrake, A., Leeth, R., Griffey, S., & Kohn, J.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
Kohn, Joachim
ORCID
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2019-02
Volume
85
Pages
75-83
ISSN
1742-7061 (ISSN-L)
DOI
10.1016/j.actbio.2018.12.006
OpenAlex
W2903371410
Cited by
63
References
1
Citations by year
2026: 6 · 2025: 10 · 2024: 11 · 2023: 8 · 2022: 7 · 2021: 6 · 2020: 9 · 2019: 6
FWCI
5.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Biomaterialia (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • StemBioSys
  • New Jersey Center for Biomaterials
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
Keywords
chondrocyte dedifferentiation, extracellular matrix, decellularized extracellular matrix, articular chondrocytes, mesenchymal stem cells, cartilage repair, cell therapy, pellet culture, ECM composition
MeSH terms
Adult, Cartilage, Articular, Cells, Cultured, Extracellular Matrix, Gene Expression Regulation, Humans, Phenotype, Plastics, Chondrocytes, Collagen Type I, Collagen Type II, Cell Proliferation, Cell Dedifferentiation, Young Adult, Mesenchymal Stem Cells

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