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Technology Insight: adult stem cells in cartilage regeneration and tissue engineering

Abstract

Articular cartilage, the load-bearing tissue of the joint, has limited repair and regeneration potential. The scarcity of treatment modalities for large chondral defects has motivated attempts to engineer cartilage tissue constructs that can meet the functional demands of this tissue in vivo. Cartilage tissue engineering requires three components: cells, scaffold, and environment. Adult stem cells, specifically multipotent mesenchymal stem cells, are considered the cell type of choice for tissue engineering, because of the ease with which they can be isolated and expanded and their multilineage differentiation capabilities. Successful outcome of cell-based cartilage tissue engineering ultimately depends on the proper differentiation of stem cells into chondrocytes and the assembly of the appropriate cartilaginous matrix to achieve the load-bearing capabilities of the natural articular cartilage. Multiple requirements, including growth factors, signaling molecules, and physical influences, need to be met. Adult mesenchymal stem-cell-based tissue engineering is a promising technology for the development of a transplantable cartilage replacement to improve joint function.

Key Points

  • Biological and tissue-based approaches to the repair and regeneration of cartilage in degenerating joint diseases (i.e. cartilage tissue engineering) are needed

  • Engineered cartilage needs to perform the major load-bearing function of cartilage, which is dependent on its extracellular matrix

  • Successful cartilage tissue engineering depends on three factors: scaffolds, cells, and environment

  • Adult mesenchymal stem cells are highly suitable as the building-block cell type for cartilage tissue engineering and regeneration, because of the ease with which they can be isolated and expanded, and their multipotential differentiation capability

  • Bioactive factors, along with the appropriate environmental cues, including mechanical stimulation and oxygen tension, are important for the differentiation of stem cells into chondrocytes for successful cartilage repair

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Figure 1: Extracellular matrix of cartilage.
Figure 2: Schematic of the cartilage tissue engineering process.
Figure 3: Multilineage differentiation potential of adult human mesenchymal stem cells.
Figure 4: Cartilage tissue engineering using biodegradable polymeric nanofibrous scaffold.

References

  1. Centers for Disease Control and Prevention (CDC) (2002) Racial/ethnic differences in the prevalence and impact of doctor-diagnosed arthritis—United States, 2002. MMWR Morb Mortal Wkly Rep 54: 119–123

  2. Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10: 432–463

    CAS  Article  Google Scholar 

  3. Mow VC et al. (2005) Structure and function of articular cartilage and meniscus. In Basic Orthopaedic Biomechanics and Mechano-Biology, 181–258 (Eds Mow VC and Huiskes R) Philadelphia: Lippincott–Raven

    Google Scholar 

  4. Langer R and Vacanti JP (1993) Tissue engineering. Science 260: 920–926

    CAS  Article  Google Scholar 

  5. Kuo CK et al. (2006) Cartilage tissue engineering: its potential and uses. Curr Opin Rheumatol 18: 64–73

    Article  Google Scholar 

  6. Li WJ et al. (2005) Electrospun nanofibrous scaffolds: production, characterization, and application for tissue engineering and drug delivery. J Biomed Nanotech 1: 1–17

    Article  Google Scholar 

  7. Mouw JK et al. (2005) Variations in matrix composition and GAG fine structure among scaffolds for cartilage tissue engineering. Osteoarthritis Cartilage 13: 828–836

    CAS  Article  Google Scholar 

  8. Wakitani S et al. (1994) Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 76: 579–592

    CAS  Article  Google Scholar 

  9. Peterson L et al. (2000) Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 374: 212–234

    Article  Google Scholar 

  10. Knutsen G et al. (2004) Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 86: 455–464

    Article  Google Scholar 

  11. Barberi T et al. (2005) Derivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS Med 2: e161

    Article  Google Scholar 

  12. Butler DL et al. (2000) Functional tissue engineering: the role of biomechanics. J Biomech Eng 122: 570–575

    CAS  Article  Google Scholar 

  13. Buschmann MD et al. (1995) Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J Cell Sci 108: 1497–1508

    CAS  PubMed  Google Scholar 

  14. Huang CY et al. (2004) Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells. Stem Cells 22: 313–323

    CAS  Article  Google Scholar 

  15. Angele P et al. (2003) Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res 21: 451–457

    CAS  Article  Google Scholar 

  16. Scherer K et al. (2004) The influence of oxygen and hydrostatic pressure on articular chondrocytes and adherent bone marrow cells in vitro. Biorheology 41: 323–333

    CAS  PubMed  Google Scholar 

  17. Murphy CL & Polak JM (2004) Control of human articular chondrocyte differentiation by reduced oxygen tension. J Cell Physiol 199: 451–459

    CAS  Article  Google Scholar 

  18. Wang DW et al. (2005) Influence of oxygen on the proliferation and metabolism of adipose derived adult stem cells. J Cell Physiol 204: 184–191

    CAS  Article  Google Scholar 

  19. Vunjak-Novakovic G et al. (2005) Bioreactor cultivation of osteochondral grafts. Orthod Craniofac Res 8: 209–218

    CAS  Article  Google Scholar 

  20. Almarza AJ and Athanasiou KA (2004) Design characteristics for the tissue engineering of cartilaginous tissues. Ann Biomed Eng 32: 2–17

    Article  Google Scholar 

  21. Friedenstein AJ et al. (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16: 381–390

    CAS  PubMed  Google Scholar 

  22. Tuan RS et al. (2003) Adult mesenchymal stem cells and cell-based tissue engineering. Arthritis Res Ther 5: 32–45

    CAS  Article  Google Scholar 

  23. Pittenger MF et al. (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–147

    CAS  Article  Google Scholar 

  24. Sethe S et al. (2006) Aging of mesenchymal stem cells. Ageing Res Rev 5: 91–116

    CAS  Article  Google Scholar 

  25. Murphy JM et al. (2002) Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum 46: 704–713

    Article  Google Scholar 

  26. Kern S et al. (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood or adipose tissue. Stem Cells [doi:10.1634/stemcells.2005-0342]

  27. Im GI et al. (2005) Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthritis Cartilage 13: 845–853

    Article  Google Scholar 

  28. Sakaguchi Y et al. (2005) Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 52: 2521–2529

    Article  Google Scholar 

  29. Heng BC et al. (2004) Directing stem cell differentiation into the chondrogenic lineage in vitro. Stem Cells 22: 1152–1167

    Article  Google Scholar 

  30. Barry F et al. (2001) Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. Exp Cell Res 268: 189–200

    CAS  Article  Google Scholar 

  31. Sekiya I et al. (2005) Comparison of effect of BMP-2, -4, and -6 on in vitro cartilage formation of human adult stem cells from bone marrow stroma. Cell Tissue Res 320: 269–276

    CAS  Article  Google Scholar 

  32. Shirasawa S et al. (2005) In vitro chondrogenesis of human synovium-derived mesenchymal stem cells: optimal condition and comparison with bone marrow-derived cells. J Cell Biochem 97: 84–97

    Article  Google Scholar 

  33. Denker AE et al. (1995) Formation of cartilage-like spheroids by micromass cultures of murine C3H10T1/2 cells upon treatment with transforming growth factor-beta 1. Differentiation 59: 25–34

    CAS  Article  Google Scholar 

  34. Denker AE et al. (1999) Chondrogenic differentiation of murine C3H10T1/2 multipotential mesenchymal cells: I. Stimulation by bone morphogenetic protein-2 in high-density micromass cultures. Differentiation 64: 67–76

    CAS  Article  Google Scholar 

  35. Shea CM et al. (2003) BMP treatment of C3H10T1/2 mesenchymal stem cells induces both chondrogenesis and osteogenesis. J Cell Biochem 90: 1112–1127

    CAS  Article  Google Scholar 

  36. Schmitt B et al. (2003) BMP2 initiates chondrogenic lineage development of adult human mesenchymal stem cells in high-density culture. Differentiation 71: 567–577

    CAS  Article  Google Scholar 

  37. Nochi H et al. (2004) Adenovirus mediated BMP-13 gene transfer induces chondrogenic differentiation of murine mesenchymal progenitor cells. J Bone Miner Res 19: 111–122

    CAS  Article  Google Scholar 

  38. Coleman CM and Tuan RS (2003) Functional role of growth/differentiation factor 5 in chondrogenesis of limb mesenchymal cells. Mech Dev 120: 823–836

    CAS  Article  Google Scholar 

  39. Katayama R et al. (2004) Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow. Rheumatology (Oxford) 43: 980–985

    CAS  Article  Google Scholar 

  40. Mastrogiacomo M et al. (2001) Effect of different growth factors on the chondrogenic potential of human bone marrow stromal cells. Osteoarthritis Cartilage 9 (Suppl A): S36–S40

    Article  Google Scholar 

  41. Solchaga LA et al. (2005) FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J Cell Physiol 203: 398–409

    CAS  Article  Google Scholar 

  42. Loughlin J et al. (2004) Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc Natl Acad Sci USA 101: 9757–9762

    CAS  Article  Google Scholar 

  43. Yano F et al. (2005) The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner. Biochem Biophys Res Commun 333: 1300–1308

    CAS  Article  Google Scholar 

  44. Zhou S et al. (2004) Cooperation between TFG-beta and Wnt pathways during chondrocyte and adipocyte differentiation of human marrow stromal cells. J Bone Miner Res 19: 463–470

    CAS  Article  Google Scholar 

  45. Fischer L et al. (2002) Wnt-3A enhances bone morphogenetic protein-2-mediated chondrogenesis of murine C3H10T1/2 mesenchymal cells. J Biol Chem 277: 30870–30878

    CAS  Article  Google Scholar 

  46. Tuli R et al. (2003) Transforming growth factor-beta-mediated chondrogenesis of human mesenchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk. J Biol Chem 278: 41227–41236

    CAS  Article  Google Scholar 

  47. Boland GM et al. (2004) Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem 93: 1210–1230

    CAS  Article  Google Scholar 

  48. Murphy JM et al. (2003) Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 48: 3464–3474

    Article  Google Scholar 

  49. Awad HA et al. (2004) Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 25: 3211–3222

    CAS  Article  Google Scholar 

  50. Huang CY et al. (2004) Chondrogenesis of human bone marrow-derived mesenchymal stem cells in agarose culture. Anat Rec A Discov Mol Cell Evol Biol 278: 428–436

    Article  Google Scholar 

  51. Mauck RL et al. (2005) Chondrogenic differentiation and functional maturation of bovine mesenchymal stem cells in long-term agarose culture. Osteoarthritis Cartilage 14: 179–189

    Article  Google Scholar 

  52. Majumdar MK et al. (2001) BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1. J Cell Physiol 189: 275–284

    CAS  Article  Google Scholar 

  53. Wang Y et al. (2005) In vitro cartilage tissue engineering with 3D porous aqueous-derived silk scaffolds and mesenchymal stem cells. Biomaterials 26: 7082–7094

    CAS  Article  Google Scholar 

  54. Williams CG et al. (2003) In vitro chondrogenesis of bone marrow-derived mesenchymal stem cells in a photopolymerizing hydrogel. Tissue Eng 9: 679–688

    CAS  Article  Google Scholar 

  55. Noth U et al. (2002) In vitro engineered cartilage constructs produced by press-coating biodegradable polymer with human mesenchymal stem cells. Tissue Eng 8: 131–144

    CAS  Article  Google Scholar 

  56. Wakitani S et al. (2002) Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage 10: 199–206

    CAS  Article  Google Scholar 

  57. Li WJ et al. (2005) Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. Biomaterials 26: 5158–5166

    CAS  Article  Google Scholar 

  58. Li WJ et al. (2005) A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells. Biomaterials 26: 599–609

    CAS  Article  Google Scholar 

  59. Li WJ et al. (2003) Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(epsilon-caprolactone) scaffolds. J Biomed Mater Res 67A: 1105–1114

    CAS  Article  Google Scholar 

  60. Song L and Tuan RS (2004) Transdifferentiation potential of human mesenchymal stem cells derived from bone marrow. FASEB J 18: 980–982

    CAS  Article  Google Scholar 

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Acknowledgements

This work is supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH (Z01 AR41113).

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Correspondence to Rocky S Tuan.

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Chen, F., Rousche, K. & Tuan, R. Technology Insight: adult stem cells in cartilage regeneration and tissue engineering. Nat Rev Rheumatol 2, 373–382 (2006). https://doi.org/10.1038/ncprheum0216

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