Review
Chondrogenesis and cartilage tissue engineering: the longer road to technology development

https://doi.org/10.1016/j.tibtech.2011.09.002Get rights and content

Joint injury and disease are painful and debilitating conditions affecting a substantial proportion of the population. The idea that damaged cartilage in articulating joints might be replaced seamlessly with tissue-engineered cartilage is of obvious commercial interest because the market for such treatments is large. Recently, a wealth of new information about the complex biology of chondrogenesis and cartilage has emerged from stem cell research, including increasing evidence of the role of physical stimuli in directing differentiation. The challenge for the next generation of tissue engineers is to identify the key elements in this new body of knowledge that can be applied to overcome current limitations affecting cartilage synthesis in vitro. Here we review the status of cartilage tissue engineering and examine the contribution of stem cell research to technology development for cartilage production.

Section snippets

Cartilage tissue engineering: prospects and challenges

Articular cartilage has little capacity for self-repair but a relatively high incidence of damage and deterioration from common trauma such as sports injury and diseases such as osteoarthritis. Surgical procedures such as autologous chondrocyte implantation for cell-based repair of small chondral lesions, and subchondral bone drilling or microfracture to activate cartilage synthesis by progenitor cells, are practiced clinically. However, despite providing temporary relief from the symptoms of

Cartilage from differentiated chondrocytes

Cartilage tissue engineering using chondrocytes has been studied extensively and many three-dimensional scaffold and bioreactor culture systems have been developed. Chondrocytes are isolated from cartilage tissue, but useful quantities of healthy human cartilage from load-bearing joints are difficult to source because of the high risk of joint injury at the donor site. Consequently, most tissue engineering studies using differentiated chondrocytes have employed animal models or human fetal

Cartilage from mesenchymal stem cells

Ongoing ethical issues and immunorejection problems using embryonic stem cells and unresolved safety concerns about the tumorigenicity of embryonic and induced pluripotent stem cells [12] mean that tissue-derived mesenchymal stem cells represent the most practical stem cell type for cartilage tissue engineering. In particular, adipose-derived stem cells are an attractive resource for clinical applications. Adipose tissue is easy to access and in plentiful supply in most patients; mesenchymal

Other cell sources for cartilage production

It is possible that neither differentiated chondrocytes nor mesenchymal stem cells are the optimal starting cell type for cartilage tissue engineering. In vivo, these cells mediate normal wound responses and are responsible for the formation of scar tissue. Persistent expression of collagen type I and the production of fibrocartilage by cultured chondrocytes and chondroinduced stem cells could be a reflection of the role these cells play in healing damaged cartilage. Such wound responses are

Concluding remarks and future perspectives

Omics studies are enabling us to develop a deeper appreciation of the biochemical and physiological complexity of differentiation and tissue development. However, culture systems for producing functional tissues outside of the body have not yet been improved substantially by the current emphasis on investigating the molecular basis of stem cell differentiation. In many ways, this recent research has highlighted the extent of the difficulties affecting in vitro cartilage development.

The role of

Acknowledgments

Our work was funded by the Australian Research Council (ARC).

References (84)

  • S.R. Tew et al.

    Regulation of SOX9 mRNA in human articular chondrocytes involving p38 MAPK activation and mRNA stabilization

    J. Biol. Chem.

    (2006)
  • A. Mammoto et al.

    Cytoskeletal control of growth and cell fate switching

    Curr. Opin. Cell Biol.

    (2009)
  • F. Guilak

    Control of stem cell fate by physical interactions with the extracellular matrix

    Cell Stem Cell

    (2009)
  • A.H. Huang

    Mechanics and mechanobiology of mesenchymal stem cell-based engineered cartilage

    J. Biomech.

    (2010)
  • C.T. Buckley

    Oxygen tension differentially regulates the functional properties of cartilaginous tissues engineered from infrapatellar fat pad derived MSCs and articular chondrocytes

    Osteoarthr. Cartilage

    (2010)
  • C. Haasper

    A system for engineering an osteochondral construct in the shape of an articular surface: preliminary results

    Ann. Anat.

    (2008)
  • W.L. Grayson

    Spatial regulation of human mesenchymal stem cell differentiation in engineered osteochondral constructs: effects of pre-differentiation, soluble factors and medium perfusion

    Osteoarthr. Cartilage

    (2010)
  • C. Hidaka

    Enhanced matrix synthesis and in vitro formation of cartilage-like tissue by genetically modified chondrocytes expressing BMP-7

    J. Orthop. Res.

    (2001)
  • J.J. Wood

    Autologous cultured chondrocytes: adverse events reported to the United States Food and Drug Administration

    J. Bone Joint Surg.

    (2006)
  • C.M. Revell et al.

    Success rates and immunologic responses of autogenic, allogenic, and xenogenic treatments to repair articular cartilage defects

    Tissue Eng. B

    (2009)
  • L.E. Freed

    Composition of cell–polymer cartilage implants

    Biotechnol. Bioeng.

    (1994)
  • N.S. Dunkelman

    Cartilage production by rabbit articular chondrocytes on polyglycolic acid scaffolds in a closed bioreactor system

    Biotechnol. Bioeng.

    (1995)
  • B.A. Byers

    Transient exposure to transforming growth factor beta 3 under serum-free conditions enhances the biomechanical and biochemical maturation of tissue-engineered cartilage

    Tissue Eng. A

    (2008)
  • G.N. Duda

    Mechanical quality of tissue engineered cartilage: results after 6 and 12 weeks in vivo

    J. Biomed. Mater. Res. B Appl. Biomater.

    (2000)
  • D.E. Ingber

    Tissue engineering and developmental biology: going biomimetic

    Tissue Eng.

    (2006)
  • P. Lenas

    Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part I: from three-dimensional cell growth to biomimetics of in vivo development

    Tissue Eng. B

    (2009)
  • C. Scotti

    Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering

    Proc. Natl. Acad. Sci. U.S.A.

    (2010)
  • J. Hanley

    An introduction to induced pluripotent stem cells

    Br. J. Haematol.

    (2010)
  • I.E. Erickson

    Differential maturation and structure–function relationships in mesenchymal stem cell- and chondrocyte-seeded hydrogels

    Tissue Eng. A

    (2009)
  • A.H. Huang

    Evaluation of the complex transcriptional topography of mesenchymal stem cell chondrogenesis for cartilage tissue engineering

    Tissue Eng. A

    (2010)
  • N. Mahmoudifar et al.

    Extent of cell differentiation and capacity for cartilage synthesis in human adult adipose-derived stem cells: comparison with fetal chondrocytes

    Biotechnol. Bioeng.

    (2010)
  • I. Sekiya

    In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis

    Proc. Natl. Acad. Sci. U.S.A.

    (2002)
  • K. Pelttari

    Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice

    Arthritis Rheum.

    (2006)
  • J. Xu

    Chondrogenic differentiation of human mesenchymal stem cells in three-dimensional alginate gels

    Tissue Eng. A

    (2008)
  • B.T. Estes

    Extended passaging, but not aldehyde dehydrogenase activity, increases the chondrogenic potential of human adipose-derived adult stem cells

    J. Cell. Physiol.

    (2006)
  • H.-J. Kim et al.

    Chondrogenic differentiation of adipose tissue-derived mesenchymal stem cells: greater doses of growth factor are necessary

    J. Orthop. Res.

    (2009)
  • M.B. Mueller et al.

    Functional characterization of hypertrophy in chondrogenesis of human mesenchymal stem cells

    Arthritis Rheum.

    (2008)
  • S. Chen

    Coculture of synovium-derived stem cells and nucleus pulposus cells in serum-free defined medium with supplementation of transforming growth factor-β1

    Spine

    (2009)
  • J. Fischer

    Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis

    Arthritis Rheum.

    (2010)
  • V. Nelea

    Selective inhibition of type X collagen expression in human mesenchymal stem cell differentiation on polymer substrates surface-modified by glow discharge plasma

    J. Biomed. Mater. Res. A

    (2005)
  • M.P. Lutolf

    Designing materials to direct stem-cell fate

    Nature

    (2009)
  • N. Huebsch

    Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate

    Nat. Mater.

    (2010)
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