Stem Cells for Temporomandibular Joint Repair and Regeneration

Abstract

Temporomandibular Disorders (TMD) represent a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles and/or associated structures. They are a major cause of non-dental orofacial pain. As a group, they are often multi-factorial in nature and have no common etiology or biological explanations. TMD can be broadly divided into masticatory muscle and TMJ disorders. TMJ disorders are characterized by intra-articular positional and/or structural abnormalities. The most common type of TMJ disorders involves displacement of the TMJ articular disc that precedes progressive degenerative changes of the joint leading to osteoarthritis (OA). In the past decade, progress made in the development of stem cell-based therapies and tissue engineering have provided alternative methods to attenuate the disease symptoms and even replace the diseased tissue in the treatment of TMJ disorders. Resident mesenchymal stem cells (MSCs) have been isolated from the synovia of TMJ, suggesting an important role in the repair and regeneration of TMJ. The seminal discovery of pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have provided promising cell sources for drug discovery, transplantation as well as for tissue engineering of TMJ condylar cartilage and disc. This review discusses the most recent advances in development of stem cell-based treatments for TMJ disorders through innovative approaches of cell-based therapeutics, tissue engineering and drug discovery.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. 1.

    Jerjes, W., Upile, T., Abbas, S., Kafas, P., Vourvachis, M., Rob, J., et al. (2008). Muscle disorders and dentition-related aspects in temporomandibular disorders: controversies in the most commonly used treatment modalities. International Archives of Medicine, 1(1), 23.

    PubMed Central  PubMed  Article  Google Scholar 

  2. 2.

    Mountziaris, P. M., Kramer, P. R., & Mikos, A. G. (2009). Emerging intra-articular drug delivery systems for the temporomandibular joint. Methods, 47(2), 134–140.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  3. 3.

    Rigon, M., Pereira, L.M., Bortoluzzi, M.C., Loguercio, A.D., Ramos, A.L., & Cardoso, J.R. (2011). Arthroscopy for temporomandibular disorders. The Cochrane Library, Cd006385.

  4. 4.

    Murphy, M. K., MacBarb, R. F., Wong, M. E., & Athanasiou, K. A. (2012). Temporomandibular disorders: a review of etiology, clinical management, and tissue engineering strategies. The International Journal of Oral & Maxillofacial Implants, 28(6), e393–e414.

    Article  Google Scholar 

  5. 5.

    LeResche, L. (1997). Epidemiology of temporomandibular disorders: implications for the investigation of etiologic factors. Critical Reviews in Oral Biology & Medicine, 8(3), 291–305.

    CAS  Article  Google Scholar 

  6. 6.

    Guarda-Nardini, L., Piccotti, F., Mogno, G., Favero, L., & Manfredini, D. (2012). Age-related differences in temporomandibular disorder diagnoses. CRANIO®, 30(2), 103–109.

    Google Scholar 

  7. 7.

    Peck, C. C., Goulet, J. P., Lobbezoo, F., Schiffman, E. L., Alstergren, P., Anderson, G., et al. (2014). Expanding the taxonomy of the diagnostic criteria for temporomandibular disorders. Journal of Oral Rehabilitation, 41(1), 2–23.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  8. 8.

    de Leeuw, R., & Klasser, G. D. (2013). Orofacial pain: Guidelines for assessment, diagnosis, and management. Chicago: Quintessence Publishing Co, Inc.

    Google Scholar 

  9. 9.

    Klausner, J. J. (1994). Epidemiologic studies reveal trends in temporomandibular pain and dysfunction. Journal of the Massachusetts Dental Society, 44(1), 21–25.

    Google Scholar 

  10. 10.

    Wright, E. F., & North, S. L. (2009). Management and treatment of temporomandibular disorders: a clinical perspective. Journal of Manual & Manipulative Therapy, 17(4), 247–254.

    Article  Google Scholar 

  11. 11.

    Tanaka, E., Detamore, M. S., & Mercuri, L. G. (2008). Degenerative disorders of the temporomandibular joint: etiology, diagnosis, and treatment. Journal of Dental Research, 87(4), 296–307.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Mujakperuo, H.R., Watson, M., Morrison, R., & Macfarlane, T.V. (2010). Pharmacological interventions for pain in patients with temporomandibular disorders. The Cochrane Library, Cd004715.

  13. 13.

    Gundlach, K. K. (1990). Long-term results following surgical treatment of internal derangement of the temporomandibular joint. Journal of Cranio-Maxillofacial Surgery, 18(5), 206–209.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Dimitroulis, G. (2011). Condylar morphology after temporomandibular joint discectomy with interpositional abdominal dermis-fat graft. Journal of Oral and Maxillofacial Surgery, 69(2), 439–446.

    PubMed  Article  Google Scholar 

  15. 15.

    González-García, R. (2015). The current role and the future of minimally invasive temporomandibular joint surgery. Oral and Maxillofacial Surgery Clinics of North America, 27(1), 69–84.

    PubMed  Article  Google Scholar 

  16. 16.

    Dionne, R. A. (1997). Pharmacologic treatments for temporomandibular disorders. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 83(1), 134–142.

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    Long, X., Chen, G., Cheng, A. H., Cheng, Y., Deng, M., Cai, H., et al. (2009). A randomized controlled trial of superior and inferior temporomandibular joint space injection with hyaluronic acid in treatment of anterior disc displacement without reduction. Journal of Oral and Maxillofacial Surgery, 67(2), 357–361.

    PubMed  Article  Google Scholar 

  18. 18.

    Agus, B., Weisberg, J., & Friedman, M. H. (1983). Therapeutic injection of the temporomandibular joint. Oral Surgery, Oral Medicine, Oral Pathology, 55(6), 553–555.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Detamore, M. S., & Athanasiou, K. A. (2005). Evaluation of three growth factors for TMJ disc tissue engineering. Annals of Biomedical Engineering, 33(3), 383–390.

    PubMed Central  PubMed  Article  Google Scholar 

  20. 20.

    Johns, D. E., Wong, M. E., & Athanasiou, K. A. (2008). Clinically relevant cell sources for TMJ disc engineering. Journal of Dental Research, 87(6), 548–552.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  21. 21.

    Anderson, D. E. J., & Athanasiou, K. A. (2009). A comparison of primary and passaged chondrocytes for use in engineering the temporomandibular joint. Archives of Oral Biology, 54(2), 138–145.

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Allen, K. D., & Athanasiou, K. A. (2007). Effect of passage and topography on gene expression of temporomandibular joint disc cells. Tissue Engineering, 13(1), 101–110.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Wu, Y., Gong, Z., Li, J., Meng, Q., Fang, W., & Long, X. (2014). The pilot study of fibrin with temporomandibular joint derived synovial stem cells in repairing TMJ disc perforation. BioMediciine Research International, 2014, 454021.

    Google Scholar 

  24. 24.

    Ahtiainen, K., Mauno, J., Ellä, V., Hagström, J., Lindqvist, C., Miettinen, S., et al. (2013). Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc. Journal of the Royal Society Interface, 10(85), 20130287.

    PubMed Central  Article  CAS  Google Scholar 

  25. 25.

    Alhadlaq, A., Elisseeff, J. H., Hong, L., Williams, C. G., Caplan, A. I., Sharma, B., et al. (2004). Adult stem cell driven genesis of human-shaped articular condyle. Annals of Biomedical Engineering, 32(7), 911–923.

    PubMed  Article  Google Scholar 

  26. 26.

    Zhang, J., Guo, F., Mi, J., & Zhang, Z. (2014). Periodontal ligament mesenchymal stromal cells increase proliferation and glycosaminoglycans formation of temporomandibular joint derived fibrochondrocytes. BioMedicine Research International, 2014, 410167.

    Google Scholar 

  27. 27.

    da Silva Meirelles, L., Fontes, A. M., Covas, D. T., & Caplan, A. I. (2009). Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine and Growth Factor Reviews, 20(5), 419–427.

    Article  CAS  Google Scholar 

  28. 28.

    Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861–872.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Wang, L., Tran, I., Seshareddy, K., Weiss, M. L., & Detamore, M. S. (2009). A comparison of human bone marrow—derived mesenchymal stem cells and human umbilical cord—derived mesenchymal stromal cells for cartilage tissue engineering. Tissue Engineering Part A, 15(8), 2259–2266.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Chen, K., Man, C., Zhang, B., Hu, J., & Zhu, S. S. (2013). Effect of in vitro chondrogenic differentiation of autologous mesenchymal stem cells on cartilage and subchondral cancellous bone repair in osteoarthritis of temporomandibular joint. International Journal of Oral and Maxillofacial Surgery, 42(2), 240–248.

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Zheng, Y. H., Su, K., Jian, Y. T., Kuang, S. J., & Zhang, Z. G. (2011). Basic fibroblast growth factor enhances osteogenic and chondrogenic differentiation of human bone marrow mesenchymal stem cells in coral scaffold constructs. Journal of Tissue Engineering and Regenerative Medicine, 5(7), 540–550.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Toh, W. S., Liu, H., Heng, B. C., Rufaihah, A. J., Ye, C. P., & Cao, T. (2005). Combined effects of TGFβ1 and BMP2 in serum-free chondrogenic differentiation of mesenchymal stem cells induced hyaline-like cartilage formation. Growth Factors, 23(4), 313–321.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Ciocca, L., Donati, D., Ragazzini, S., Dozza, B., Rossi, F., Fantini, M., et al. (2013) Mesenchymal stem cells and platelet gel improve bone deposition within CAD-CAM custom-made ceramic HA scaffolds for condyle substitution. BioMedicine Research International, 2013, 549762.

  35. 35.

    Cao, B., Zheng, B., Jankowski, R. J., Kimura, S., Ikezawa, M., Deasy, B., et al. (2003) Muscle stem cells differentiate into haematopoietic lineages but retain myogenic potential. Nature Cell Biology, 5(7), 640646.

  36. 36.

    Gao, Y., Bai, C., Xiong, H., Li, Q., Shan, Z., Huang, L., et al. (2013) Isolation and characterization of chicken dermis-derived mesenchymal stem/progenitor cells. BioMedicine Research International. 2013, 626258.

  37. 37.

    Wu, L., Cai, X., Zhang, S., Karperien, M., & Lin, Y. (2013). Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine. Journal of Cellular Physiology, 228(5), 938–944.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Gimble, J. M., & Guilak, F. (2003). Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy, 5(5), 362–369.

    PubMed  Article  Google Scholar 

  39. 39.

    Fu, W. L., Zhou, C. Y., & Yu, J. K. (2014). A new source of mesenchymal stem cells for articular cartilage repair: MSCs derived From mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model. The American Journal of Sports Medicine, 42(3), 592–601.

    PubMed  Article  Google Scholar 

  40. 40.

    Huang, G. J., Gronthos, S., & Shi, S. (2009). Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. Journal of Dental Research, 88(9), 792–806.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  41. 41.

    De Bari, C., Dell’Accio, F., Tylzanowski, P., & Luyten, F. P. (2001). Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis and Rheumatism, 44(8), 1928–1942.

    PubMed  Article  Google Scholar 

  42. 42.

    Jones, B. A., & Pei, M. (2012). Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration. Tissue Engineering, Part B: Reviews, 18(4), 301–311.

    CAS  Article  Google Scholar 

  43. 43.

    Koyama, N., Okubo, Y., Nakao, K., Osawa, K., Fujimura, K., & Bessho, K. (2011). Pluripotency of mesenchymal cells derived from synovial fluid in patients with temporomandibular joint disorder. Life Sciences, 89(19), 741–747.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Liu, Z., Long, X., Li, J., Wei, L., Gong, Z., Fang, W. (2011). Differentiation of temporomandibular joint synovial mesenchymal stem cells into neuronal cells in vitro: an in vitro study. Cell Biology International, 35(1), 87–91.

  45. 45.

    Sun, Y. P., Zheng, Y. H., Liu, W. J., Zheng, Y. L., & Zhang, Z. G. (2014). Synovium fragment-derived cells exhibit characteristics similar to those of dissociated multipotent cells in synovial fluid of the temporomandibular joint. PLoS ONE, 9(7), e101896.

    PubMed Central  PubMed  Article  Google Scholar 

  46. 46.

    Futami, I., Ishijima, M., Kaneko, H., Tsuji, K., Ichikawa-Tomikawa, N., Sadatsuki, R., et al. (2012). Isolation and characterization of multipotential mesenchymal cells from the mouse synovium. PLoS ONE, 7(9), e45517.

  47. 47.

    Pizzute, T., Lynch, K., & Pei, M. (2015). Impact of tissue-specific stem cells on lineage-specific differentiation: a focus on the musculoskeletal system. Stem Cell Reviews and Reports, 11(1), 119–132.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Sakaguchi, Y., Sekiya, I., Yagishita, K., & Muneta, T. (2005). Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis and Rheumatism, 52(8), 2521–2529.

    PubMed  Article  Google Scholar 

  49. 49.

    Pei, M., He, F., Boyce, B. M., & Kish, V. L. (2009). Repair of full-thickness femoral condyle cartilage defects using allogeneic synovial cell-engineered tissue constructs. Osteoarthritis and Cartilage, 17(6), 714–722.

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Yoshimura, H., Muneta, T., Nimura, A., Yokoyama, A., Koga, H., & Sekiya, I. (2007). Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell and Tissue Research, 327(3), 449–462.

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Handorf, A. M., & Li, W. J. (2014). Induction of mesenchymal stem cell chondrogenesis through sequential administration of growth factors within specific temporal windows. Journal of Cellular Physiology, 229(2), 162–171.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Shirasawa, S., Sekiya, I., Sakaguchi, Y., Yagishita, K., Ichinose, S., & Muneta, T. (2006). In vitro chondrogenesis of human synovium‐derived mesenchymal stem cells: Optimal condition and comparison with bone marrow‐derived cells. Journal of Cellular Biochemistry, 97(1), 84–97.

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    Indrawattana, N., Chen, G., Tadokoro, M., Shann, L. H., Ohgushi, H., Tateishi, T., et al. (2004). Growth factor combination for chondrogenic induction from human mesenchymal stem cell. Biochemical and Biophysical Research Communications, 320(3), 914–919.

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    Li, J., & Pei, M. (2010). Optimization of an in vitro three-dimensional microenvironment to reprogram synovium-derived stem cells for cartilage tissue engineering. Tissue Engineering Part A, 17(5–6), 703–712.

    PubMed  Google Scholar 

  55. 55.

    Schek, R. M., Taboas, J. M., Hollister, S. J., & Krebsbach, P. H. (2005). Tissue engineering osteochondral implants for temporomandibular joint repair. Orthodontics & Craniofacial Research, 8(4), 313–319.

    CAS  Article  Google Scholar 

  56. 56.

    Handorf, A. M., & Li, W. J. (2011). Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis. PLoS ONE, 6(7), e22887.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  57. 57.

    Adesida, A. B., Mulet-Sierra, A., & Jomha, N. M. (2012). Hypoxia mediated isolation and expansion enhances the chondrogenic capacity of bone marrow mesenchymal stromal cells. Stem Cell Research & Therapy, 3(2), 1–13.

    Article  CAS  Google Scholar 

  58. 58.

    Boyette, L. B., Creasey, O. A., Guzik, L., Lozito, T., & Tuan, R. S. (2014). Human bone marrow-derived mesenchymal stem cells display enhanced clonogenicity but impaired differentiation with hypoxic preconditioning. Stem Cells Translational Medicine, 3(2), 241–254.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  59. 59.

    Toh, W. S., Foldager, C. B., Pei, M., & Hui, J. H. P. (2014). Advances in mesenchymal stem cell-based strategies for cartilage repair and regeneration. Stem Cell Reviews and Reports, 10(5), 686–696.

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Toh, W. S. (2014). Recent progress in stem cell chondrogenesis. Progress in Stem Cell, 1(1), 7–17.

    Article  Google Scholar 

  61. 61.

    Grayson, W. L., Fröhlich, M., Yeager, K., Bhumiratana, S., Chan, M. E., Cannizzaro, C., et al. (2010). Engineering anatomically shaped human bone grafts. Proceedings of the National Academy of Sciences, 107(8), 3299–3304.

    CAS  Article  Google Scholar 

  62. 62.

    O’Donoghue, K., & Chan, J. (2006). Human fetal mesenchymal stem cells. Current Stem Cell Research & Therapy, 1(3), 371–386.

    Article  Google Scholar 

  63. 63.

    Bara, J. J., McCarthy, H. E., Humphrey, E., Johnson, W. E., & Roberts, S. (2014). Bone marrow-derived mesenchymal stem cells become antiangiogenic when chondrogenically or osteogenically differentiated: implications for bone and cartilage tissue engineering. Tissue Engineering Part A, 20(1–2), 147–159.

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    Reubinoff, B. E., Pera, M. F., Fong, C. Y., Trounson, A., & Bongso, A. (2000). Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nature Biotechnology, 18(4), 399–404.

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Odorico, J. S., Kaufman, D. S., & Thomson, J. A. (2001). Multilineage differentiation from human embryonic stem cell lines. Stem Cells, 19(3), 193–204.

    CAS  PubMed  Article  Google Scholar 

  66. 66.

    Chong, J. J., Yang, X., Don, C. W., Minami, E., Liu, Y. W., Weyers, J. J., et al. (2014). Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature, 510(7504), 273–277.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  67. 67.

    Boheler, K. R., Czyz, J., Tweedie, D., Yang, H. T., Anisimov, S. V., & Wobus, A. M. (2002). Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circulation Research, 91(3), 189–201.

    CAS  PubMed  Article  Google Scholar 

  68. 68.

    Rufaihah, A. J., Haider, H. K., Heng, B. C., Ye, L., Toh, W. S., Tian, X. F., et al. (2007). Directing endothelial differentiation of human embryonic stem cells via transduction with an adenoviral vector expressing the VEGF165 gene. The Journal of Gene Medicine, 9(6), 452–461.

    CAS  PubMed  Article  Google Scholar 

  69. 69.

    Levenberg, S., Golub, J. S., Amit, M., Itskovitz-Eldor, J., & Langer, R. (2002). Endothelial cells derived from human embryonic stem cells. Proceedings of the National Academy of Sciences, 99(7), 4391–4396.

    CAS  Article  Google Scholar 

  70. 70.

    Rufaihah, A. J., Haider, H. K., Heng, B. C., Ye, L., Tan, R. S., Toh, W. S., et al. (2010). Therapeutic angiogenesis by transplantation of human embryonic stem cell-derived CD133+ endothelial progenitor cells for cardiac repair. Regenerative Medicine, 5(2), 231–244.

    CAS  PubMed  Article  Google Scholar 

  71. 71.

    Toh, W. S., Yang, Z., Liu, H., Heng, B. C., Lee, E. H., & Cao, T. (2007). Effects of culture conditions and bone morphogenetic protein 2 on extent of chondrogenesis from human embryonic stem cells. Stem Cells, 25(4), 950–960.

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Oldershaw, R. A., Baxter, M. A., Lowe, E. T., Bates, N., Grady, L. M., Soncin, F., et al. (2010). Directed differentiation of human embryonic stem cells toward chondrocytes. Nature Biotechnology, 28(11), 1187–1194.

    CAS  PubMed  Article  Google Scholar 

  73. 73.

    Toh, W. S., Lee, E. H., & Cao, T. (2011). Potential of human embryonic stem cells in cartilage tissue engineering and regenerative medicine. Stem Cell Reviews and Reports, 7(3), 544–559.

    PubMed  Article  Google Scholar 

  74. 74.

    Toh, W. S., Lee, E. H., Guo, X. M., Chan, J. K., Yeow, C. H., Choo, A. B., et al. (2010). Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells. Biomaterials, 31(27), 6968–6980.

    CAS  PubMed  Article  Google Scholar 

  75. 75.

    Toh, W. S., Guo, X. M., Choo, A. B., Lu, K., Lee, E. H., & Cao, T. (2009). Differentiation and enrichment of expandable chondrogenic cells from human embryonic stem cells in vitro. Journal of Cellular and Molecular Medicine, 13(9b), 3570–3590.

    PubMed Central  PubMed  Article  Google Scholar 

  76. 76.

    Cao, T., Heng, B. C., Ye, C. P., Liu, H., Toh, W. S., Robson, P., et al. (2005). Osteogenic differentiation within intact human embryoid bodies result in a marked increase in osteocalcin secretion after 12 days of in vitro culture, and formation of morphologically distinct nodule-like structures. Tissue and Cell, 37(4), 325–334.

    CAS  PubMed  Article  Google Scholar 

  77. 77.

    Hu, J., Smith, L. A., Feng, K., Liu, X., Sun, H., & Ma, P. X. (2010). Response of human embryonic stem cell-derived mesenchymal stem cells to osteogenic factors and architectures of materials during in vitro osteogenesis. Tissue Engineering Part A, 16(11), 3507–3514.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  78. 78.

    Heng, B. C., Toh, W. S., Pereira, B. P., Tan, B. L., Fu, X., Liu, H., et al. (2008). An autologous cell lysate extract from human embryonic stem cell (hESC) derived osteoblasts can enhance osteogenesis of hESC. Tissue and Cell, 40(3), 219–228.

    PubMed  Article  Google Scholar 

  79. 79.

    Zhang, S. C., Wernig, M., Duncan, I. D., Brüstle, O., & Thomson, J. A. (2001). In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nature Biotechnology, 19(12), 1129–1133.

    CAS  PubMed  Article  Google Scholar 

  80. 80.

    Parsons, X. H., Teng, Y. D., Parsons, J. F., Snyder, E. Y., Smotrich, D. B., & Moore, D. A. (2011). Efficient derivation of human neuronal progenitors and neurons from pluripotent human embryonic stem cells with small molecule induction. Journal of Visualized Experiments: JoVE, 56, e3273.

    PubMed  Google Scholar 

  81. 81.

    Ozolek, J. A., Jane, E. P., Esplen, J. E., Petrosko, P., Wehn, A. K., Erb, T. M., et al. (2010). In vitro neural differentiation of human embryonic stem cells using a low-density mouse embryonic fibroblast feeder protocol. Methods in Molecular Biology (Clifton, NJ), 584, 71–95.

    CAS  Article  Google Scholar 

  82. 82.

    Chan, A. A., Hertsenberg, A. J., Funderburgh, M. L., Mann, M. M., Du, Y., Davoli, K. A., et al. (2013). Differentiation of human embryonic stem cells into cells with corneal keratocyte phenotype. PLoS ONE, 8(2), e56831.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  83. 83.

    Kidwai, F. K., Liu, H., Toh, W. S., Fu, X., Jokhun, D. S., Movahednia, M. M., et al. (2013). Differentiation of human embryonic stem cells into clinically amenable keratinocytes in an autogenic environment. Journal of Investigative Dermatology, 133(3), 618–628.

    CAS  PubMed  Article  Google Scholar 

  84. 84.

    Hay, D. C., Zhao, D., Fletcher, J., Hewitt, Z. A., McLean, D., Urruticoechea‐Uriguen, A., et al. (2008). Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo. Stem Cells, 26(4), 894–902.

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Park, I. H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., et al. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 451(7175), 141–146.

    CAS  PubMed  Article  Google Scholar 

  86. 86.

    Chun, Y. S., Chaudhari, P., & Jang, Y. Y. (2010). Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease. International Journal of Biological Sciences, 6(7), 796–805.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  87. 87.

    Colman, A., & Dreesen, O. (2009). Pluripotent stem cells and disease modeling. Cell Stem Cell, 5(3), 244–247.

    CAS  PubMed  Article  Google Scholar 

  88. 88.

    Rosa, V., Toh, W. S., Cao, T., & Shim, W. (2014). Inducing pluripotency for disease modeling, drug development and craniofacial applications. Expert Opinion on Biological Therapy, 14(9), 1233–1240.

    PubMed  Article  Google Scholar 

  89. 89.

    Saha, K., & Jaenisch, R. (2009). Technical challenges in using human induced pluripotent stem cells to model disease. Cell Stem Cell, 5(6), 584–595.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  90. 90.

    Kim, M. J., Son, M. J., Son, M. Y., Seol, B., Kim, J., Park, J., et al. (2011). Generation of human induced pluripotent stem cells from osteoarthritis patient-derived synovial cells. Arthritis and Rheumatism, 63(10), 3010–3021.

    CAS  PubMed  Article  Google Scholar 

  91. 91.

    Wei, Y., Zeng, W., Wan, R., Wang, J., Zhou, Q., Qiu, S., et al. (2012). Chondrogenic differentiation of induced pluripotent stem cells from osteoarthritic chondrocytes in alginate matrix. European Cells & Materials, 23, 1–12.

    CAS  Google Scholar 

  92. 92.

    Lee, J., Kim, Y., Yi, H., Diecke, S., Kim, J., Jung, H., et al. (2014). Generation of disease-specific induced pluripotent stem cells from patients with rheumatoid arthritis and osteoarthritis. Arthritis Reseach and Therapy, 16(1), R41.

    Article  Google Scholar 

  93. 93.

    Craft, A. M., Ahmed, N., Rockel, J. S., Baht, G. S., Alman, B. A., Kandel, R. A., et al. (2013). Specification of chondrocytes and cartilage tissues from embryonic stem cells. Development, 140(12), 2597–2610.

    CAS  PubMed  Article  Google Scholar 

  94. 94.

    Khillan, J. S. (2006). Generation of chondrocytes from embryonic stem cells. Methods in Molecular Biology (Clifton, NJ), 330, 161–170.

    CAS  Google Scholar 

  95. 95.

    Heng, B. C., Cao, T., & Lee, E. H. (2004). Directing stem cell differentiation into the chondrogenic lineage in vitro. Stem Cells, 22(7), 1152–1167.

    PubMed  Article  Google Scholar 

  96. 96.

    Toh, W. S., Lee, E. H., Richards, M., & Cao, T. (2010). In vitro derivation of chondrogenic cells from human embryonic stem cells. Methods in Molecular Biology (Clifton, NJ), 584, 317–331.

    CAS  Article  Google Scholar 

  97. 97.

    Hoben, G. M., Willard, V. P., & Athanasiou, K. A. (2009). Fibrochondrogenesis of hESCs: growth factor combinations and cocultures. Stem Cells and Development, 18(2), 283–292.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  98. 98.

    Nakayama, N., Duryea, D., Manoukian, R., Chow, G., & Han, C. Y. (2003). Macroscopic cartilage formation with embryonic stem-cell-derived mesodermal progenitor cells. Journal of Cell Science, 116(10), 2015–2028.

    CAS  PubMed  Article  Google Scholar 

  99. 99.

    Yang, Z., Sui, L., Toh, W. S., Lee, E. H., & Cao, T. (2009). Stage-dependent effect of TGF-β1 on chondrogenic differentiation of human embryonic stem cells. Stem Cells and Development, 18(6), 929–940.

    CAS  PubMed  Article  Google Scholar 

  100. 100.

    Umeda, K., Zhao, J., Simmons, P., Stanley, E., Elefanty, A., & Nakayama, N. (2012). Human chondrogenic paraxial mesoderm, directed specification and prospective isolation from pluripotent stem cells. Scientific Reports, 2, 455–465.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  101. 101.

    Vats, A., Bielby, R. C., Tolley, N., Dickinson, S. C., Boccaccini, A. R., Hollander, A. P., et al. (2006). Chondrogenic differentiation of human embryonic stem cells: the effect of the micro-environment. Tissue Engineering, 12(6), 1687–1697.

    CAS  PubMed  Article  Google Scholar 

  102. 102.

    Bigdeli, N., Karlsson, C., Strehl, R., Concaro, S., Hyllner, J., & Lindahl, A. (2009). Coculture of human embryonic stem cells and human articular chondrocytes results in significantly altered phenotype and improved chondrogenic differentiation. Stem Cells, 27(8), 1812–1821.

    PubMed  Article  Google Scholar 

  103. 103.

    Hwang, N. S., Varghese, S., & Elisseeff, J. (2008). Derivation of chondrogenically-committed cells from human embryonic cells for cartilage tissue regeneration. PLoS ONE, 3(6), e2498.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  104. 104.

    Lian, Q., Lye, E., Suan Yeo, K., Khia Way Tan, E., Salto‐Tellez, M., Liu, T. M., et al. (2007). Derivation of clinically compliant MSCs from CD105+, CD24− differentiated human ESCs. Stem Cells, 25(2), 425–436.

    CAS  PubMed  Article  Google Scholar 

  105. 105.

    Olee, T., Grogan, S. P., Lotz, M. K., Colwell, C. W., Jr., D’Lima, D. D., & Snyder, E. Y. (2014). Repair of cartilage defects in arthritic tissue with differentiated human embryonic stem cells. Tissue Engineering Part A, 20(3–4), 683–692.

    PubMed Central  PubMed  Google Scholar 

  106. 106.

    Cheng, A., Kapacee, Z., Peng, J., Lu, S., Lucas, R. J., Hardingham, T. E., et al. (2014). Cartilage repair using human embryonic stem cell-derived chondroprogenitors. Stem Cells Translational Medicine, 3(11), 1287–1294.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  107. 107.

    Barberi, T., Willis, L. M., Socci, N. D., & Studer, L. (2005). Derivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS Medicine, 2(6), e161.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  108. 108.

    Chen, X., Song, X. H., Yin, Z., Zou, X. H., Wang, L. L., Hu, H., et al. (2009). Stepwise differentiation of human embryonic stem cells promotes tendon regeneration by secreting fetal tendon matrix and differentiation factors. Stem Cells, 27(6), 1276–1287.

    CAS  PubMed  Article  Google Scholar 

  109. 109.

    Karlsson, C., Emanuelsson, K., Wessberg, F., Kajic, K., Axell, M. Z., Eriksson, P. S., et al. (2009). Human embryonic stem cell-derived mesenchymal progenitors—potential in regenerative medicine. Stem Cell Research, 3(1), 39–50.

    PubMed  Article  Google Scholar 

  110. 110.

    Lee, E. J., Lee, H. N., Kang, H. J., Kim, K. H., Hur, J., Cho, H. J., et al. (2009). Novel embryoid body-based method to derive mesenchymal stem cells from human embryonic stem cells. Tissue Engineering Part A, 16(2), 705–715.

    Article  CAS  Google Scholar 

  111. 111.

    Ankrum, J., & Karp, J. M. (2010). Mesenchymal stem cell therapy: two steps forward, one step back. Trends in Molecular Medicine, 16(5), 203–209.

    PubMed Central  PubMed  Article  Google Scholar 

  112. 112.

    Lai, R. C., Tan, S. S., Teh, B. J., Sze, S. K., Arslan, F., de Kleijn, D. P., et al. (2012). Proteolytic potential of the MSC exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome. International Journal of Proteomics, 2012, 971907.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  113. 113.

    Lai, R.C., Yeo, R.W.Y., Tan, S.S., Zhang, B., Yin, Y., Sze, N.S.K., et al. (2012). Mesenchymal stem cell exosomes: The future MSC-based therapy? Mesenchymal Stem Cell Therapy, 39–61. Humana press.

  114. 114.

    MacFarlane, R. J., Graham, S. M., Davies, P. S., Korres, N., Tsouchnica, H., Heliotis, M., et al. (2013). Anti-inflammatory role and immunomodulation of mesenchymal stem cells in systemic joint diseases: potential for treatment. Expert Opinion on Therapeutic Targets, 17(3), 243–254.

    CAS  PubMed  Article  Google Scholar 

  115. 115.

    Yagi, H., Soto-Gutierrez, A., Parekkadan, B., Kitagawa, Y., Tompkins, R. G., Kobayashi, N., et al. (2010). Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplantation, 19(6), 667–679.

    PubMed Central  PubMed  Article  Google Scholar 

  116. 116.

    Sze, S. K., de Kleijn, D. P., Lai, R. C., Tan, E. K. W., Zhao, H., Yeo, K. S., et al. (2007). Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. Molecular & Cellular Proteomics, 6(10), 1680–1689.

    CAS  Article  Google Scholar 

  117. 117.

    Lee, M. J., Kim, J., Kim, M. Y., Bae, Y., Ryu, S. H., Lee, T. G., et al. (2010). Proteomic analysis of tumor necrosis factor-alpha-induced secretome of human adipose tissue-derived mesenchymal stem cells. Journal of Proteome Research, 9(4), 1754–1762.

    CAS  PubMed  Article  Google Scholar 

  118. 118.

    YlÖstalo, J. H., Bartosh, T. J., Coble, K., & Prockop, D. J. (2012). Human mesenchymal stem/stromal cells cultured as spheroids are self‐activated to produce prostaglandin E2 that directs stimulated macrophages into an anti‐inflammatory phenotype. Stem Cells, 30(10), 2283–2296.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  119. 119.

    Khan, M., Akhtar, S., Mohsin, S., Khan, N. S., & Riazuddin, S. (2011). Growth factor preconditioning increases the function of diabetes-impaired mesenchymal stem cells. Stem Cells and Development, 20(1), 67–75.

    CAS  PubMed  Article  Google Scholar 

  120. 120.

    Cho, G. W., Kang, B. Y., Kim, K. S., & Kim, S. H. (2012). Effects of valproic acid on the expression of trophic factors in human bone marrow mesenchymal stromal cells. Neuroscience Letters, 526(2), 100–105.

    CAS  PubMed  Article  Google Scholar 

  121. 121.

    Liu, G. S., Peshavariya, H. M., Higuchi, M., Chan, E. C., Dusting, G. J., & Jiang, F. (2013). Pharmacological priming of adipose‐derived stem cells for paracrine VEGF production with deferoxamine. Journal of Tissue Engineering and Regenerative Medicine. doi:10.1002/term.1796.

    Google Scholar 

  122. 122.

    Bartosh, T. J., Ylöstalo, J. H., Mohammadipoor, A., Bazhanov, N., Coble, K., Claypool, K., et al. (2010). Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proceedings of the National Academy of Sciences, 107(31), 13724–13729.

    CAS  Article  Google Scholar 

  123. 123.

    Tse, W. T., Pendleton, J. D., Beyer, W. M., Egalka, M. C., & Guinan, E. C. (2003). Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation, 75(3), 389–397.

    CAS  PubMed  Article  Google Scholar 

  124. 124.

    Krampera, M., Glennie, S., Dyson, J., Scott, D., Laylor, R., Simpson, E., & Dazzi, F. (2003). Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood, 101(9), 3722–3729.

    CAS  PubMed  Article  Google Scholar 

  125. 125.

    Liu, H., Lu, K., MacAry, P. A., Wong, K. L., Heng, A., Cao, T., et al. (2012). Soluble molecules are key in maintaining the immunomodulatory activity of murine mesenchymal stromal cells. Journal of Cell Science, 125(1), 200–208.

    CAS  PubMed  Article  Google Scholar 

  126. 126.

    English, K., Barry, F., Field-Corbett, C., & Mahon, B. (2007). IFN- gamma and TNF- alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunology Letters, 110(2), 91–100.

    CAS  PubMed  Article  Google Scholar 

  127. 127.

    Ortiz, L. A., DuTreil, M., Fattman, C., Pandey, A. C., Torres, G., Go, K., et al. (2007). Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proceedings of the National Academy of Sciences of the United States of America, 104(26), 11002–11007.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  128. 128.

    Van Koppen, A., Joles, J. A., van Balkom, B. W., Lim, S. K., de Kleijn, D., Giles, R. H., et al. (2012). Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease. PLoS ONE, 7(6), e38746.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  129. 129.

    Timmers, L., Lim, S. K., Hoefer, I. E., Arslan, F., Lai, R. C., van Oorschot, A. A., et al. (2011). Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Research, 6(3), 206–214.

    PubMed  Article  Google Scholar 

  130. 130.

    Locatelli, F., Bersano, A., Ballabio, E., Lanfranconi, S., Papadimitriou, D., Strazzer, S., et al. (2009). Stem cell therapy in stroke. Cellular and Molecular Life Sciences, 66(5), 757–772.

    CAS  PubMed  Article  Google Scholar 

  131. 131.

    Linero, I., & Chaparro, O. (2014). Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS ONE, 9(9), e107001.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  132. 132.

    Diekman, B. O., Wu, C. L., Louer, C. R., Furman, B. D., Huebner, J. L., Kraus, V. B., et al. (2013). Intra-articular delivery of purified mesenchymal stem cells from C57BL/6 or MRL/MpJ superhealer mice prevents post-traumatic arthritis. Cell Transplantation, 22(8), 1395–1408.

    PubMed Central  PubMed  Article  Google Scholar 

  133. 133.

    Horie, M., Choi, H., Lee, R. H., Reger, R. L., Ylostalo, J., Muneta, T., et al. (2012). Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthritis and Cartilage, 20(10), 1197–1207.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  134. 134.

    Van Buul, G. M., Villafuertes, E., Bos, P. K., Waarsing, J. H., Kops, N., Narcisi, R., et al. (2012). Mesenchymal stem cells secrete factors that inhibit inflammatory processes in short-term osteoarthritic synovium and cartilage explant culture. Osteoarthritis and Cartilage, 20(10), 1186–1196.

    PubMed  Article  Google Scholar 

  135. 135.

    Wu, L., Leijten, J. C., Georgi, N., Post, J. N., van Blitterswijk, C. A., & Karperien, M. (2011). Trophic effects of mesenchymal stem cells increase chondrocyte proliferation and matrix formation. Tissue Engineering Part A, 17(9–10), 1425–1436.

    CAS  PubMed  Article  Google Scholar 

  136. 136.

    Wu, L., Prins, H. J., Helder, M. N., van Blitterswijk, C. A., & Karperien, M. (2012). Trophic effects of mesenchymal stem cells in chondrocyte co-cultures are independent of culture conditions and cell sources. Tissue Engineering Part A, 18(15–16), 1542–1551.

    CAS  PubMed  Article  Google Scholar 

  137. 137.

    Petrovic, V., Zivkovic, P., Petrovic, D., & Stefanovic, V. (2012). Craniofacial bone tissue engineering. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 114(3), e1–e9.

    PubMed  Article  Google Scholar 

  138. 138.

    Toh, W. S., Spector, M., Lee, E. H., & Cao, T. (2011). Biomaterial-mediated delivery of microenvironmental cues for repair and regeneration of articular cartilage. Molecular Pharmaceutics, 8(4), 994–1001.

    CAS  PubMed  Article  Google Scholar 

  139. 139.

    Allen, K. D., & Athanasiou, K. A. (2008). Scaffold and growth factor selection in temporomandibular joint disc engineering. Journal of Dental Research, 87(2), 180–185.

    CAS  PubMed  Article  Google Scholar 

  140. 140.

    Almarza, A. J., & Athanasiou, K. A. (2004). Seeding techniques and scaffolding choice for tissue engineering of the temporomandibular joint disc. Tissue Engineering, 10(11–12), 1787–1795.

    CAS  PubMed  Article  Google Scholar 

  141. 141.

    Chung, C., & Burdick, J. A. (2008). Engineering cartilage tissue. Advanced Drug Delivery Reviews, 60(2), 243–262.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  142. 142.

    Mao, J. J., Giannobile, W. V., Helms, J. A., Hollister, S. J., Krebsbach, P. H., Longaker, M. T., et al. (2006). Craniofacial tissue engineering by stem cells. Journal of Dental Research, 85(11), 966–979.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  143. 143.

    Nicodemus, G. D., Villanueva, I., & Bryant, S. J. (2007). Mechanical stimulation of TMJ condylar chondrocytes encapsulated in PEG hydrogels. Journal of Biomedical Materials Research, Part A, 83(2), 323–331.

    Article  CAS  Google Scholar 

  144. 144.

    Toh, W. S., Lim, T. C., Kurisawa, M., & Spector, M. (2012). Modulation of mesenchymal stem cell chondrogenesis in a tunable hyaluronic acid hydrogel microenvironment. Biomaterials, 33(15), 3835–3845.

    CAS  PubMed  Article  Google Scholar 

  145. 145.

    MacBarb, R. F., Chen, A. L., Hu, J. C., & Athanasiou, K. A. (2013). Engineering functional anisotropy in fibrocartilage neotissues. Biomaterials, 34(38), 9980–9989.

    CAS  PubMed  Article  Google Scholar 

  146. 146.

    Toh, W. S., & Loh, X. J. (2014). Advances in hydrogel delivery systems for tissue regeneration. Materials Science and Engineering: C, 45, 690–697.

    CAS  Article  Google Scholar 

  147. 147.

    Detamore, M. S., & Athanasiou, K. A. (2003). Motivation, characterization, and strategy for tissue engineering the temporomandibular joint disc. Tissue Engineering, 9(6), 1065–1087.

    CAS  PubMed  Article  Google Scholar 

  148. 148.

    Moioli, E. K., Clark, P. A., Xin, X., Lal, S., & Mao, J. J. (2007). Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering. Advanced Drug Delivery Reviews, 59(4), 308–324.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  149. 149.

    Toh, W.S., Toh, Y.C., & Loh, X.J. (2015). Hydrogels for stem cell fate control and delivery in regenerative medicine. In: In-situ gelling polymers 187–214. Springer Singapore. doi:10.1007/978-981-287-152-7_8

  150. 150.

    Hagandora, C. K., Gao, J., Wang, Y., & Almarza, A. J. (2013). Poly (glycerol sebacate): a novel scaffold material for temporomandibular joint disc engineering. Tissue Engineering Part A, 19(5–6), 729–737.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  151. 151.

    Allen, K. D., & Athanasiou, K. A. (2006). Tissue engineering of the TMJ disc: a review. Tissue Engineering, 12(5), 1183–1196.

    PubMed  Article  Google Scholar 

  152. 152.

    Brown, B. N., Chung, W. L., Almarza, A. J., Pavlick, M., Reppas, S., Ochs, M. W., & Badylak, S. F. (2012). An inductive, scaffold-based, regenerative medicine approach to reconstruction of the temporomandibular joint disk. Journal of Oral and Maxillofacial Surgery, 70(11), 2656–2668.

    PubMed Central  PubMed  Article  Google Scholar 

  153. 153.

    Dimitroulis, G. (2005). The use of dermis grafts after discectomy for internal derangement of the temporomandibular joint. Journal of Oral and Maxillofacial Surgery, 63(2), 173–178.

    PubMed  Article  Google Scholar 

  154. 154.

    Thyne, G. M., Yoon, J. H., Luyk, N. H., & McMillan, M. D. (1992). Temporalis muscle as a disc replacement in the temporomandibular joint of sheep. Journal of Oral and Maxillofacial Surgery, 50(9), 979–987.

    CAS  PubMed  Article  Google Scholar 

  155. 155.

    Schek, R. M., Taboas, J. M., Segvich, S. J., Hollister, S. J., & Krebsbach, P. H. (2004). Engineered osteochondral grafts using biphasic composite solid free-form fabricated scaffolds. Tissue Engineering, 10(9–10), 1376–1385.

    CAS  PubMed  Article  Google Scholar 

  156. 156.

    Alhadlaq, A., & Mao, J. J. (2005). Tissue-engineered osteochondral constructs in the shape of an articular condyle. The Journal of Bone and Joint Surgery, 87(5), 936–944.

    PubMed  Article  Google Scholar 

  157. 157.

    Lutolf, M. P., & Hubbell, J. A. (2005). Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nature Biotechnology, 23(1), 47–55.

    CAS  PubMed  Article  Google Scholar 

  158. 158.

    Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126(4), 677–689.

    CAS  PubMed  Article  Google Scholar 

  159. 159.

    Lim, T. C., Toh, W. S., Wang, L. S., Kurisawa, M., & Spector, M. (2012). The effect of injectable gelatin-hydroxyphenylpropionic acid hydrogel matrices on the proliferation, migration, differentiation and oxidative stress resistance of adult neural stem cells. Biomaterials, 33(12), 3446–3455.

    CAS  PubMed  Article  Google Scholar 

  160. 160.

    Wang, L. S., Boulaire, J., Chan, P. P., Chung, J. E., & Kurisawa, M. (2010). The role of stiffness of gelatin-hydroxyphenylpropionic acid hydrogels formed by enzyme-mediated crosslinking on the differentiation of human mesenchymal stem cell. Biomaterials, 31(33), 8608–8616.

    CAS  PubMed  Article  Google Scholar 

  161. 161.

    Wang, L. S., Du, C., Toh, W. S., Wan, A. C., Gao, S. J., & Kurisawa, M. (2014). Modulation of chondrocyte functions and stiffness-dependent cartilage repair using an injectable enzymatically crosslinked hydrogel with tunable mechanical properties. Biomaterials, 35(7), 2207–2217.

    CAS  PubMed  Article  Google Scholar 

  162. 162.

    Almarza, A. J., & Athanasiou, K. A. (2006). Effects of hydrostatic pressure on TMJ disc cells. Tissue Engineering, 12(5), 1285–1294.

    PubMed  Article  Google Scholar 

  163. 163.

    Terraciano, V., Hwang, N., Moroni, L., Park, H. B., Zhang, Z., Mizrahi, J., et al. (2007). Differential response of adult and embryonic mesenchymal progenitor cells to mechanical compression in hydrogels. Stem Cells, 25(11), 2730–2738.

    CAS  PubMed  Article  Google Scholar 

  164. 164.

    Steinmetz, N. J., & Bryant, S. J. (2012). Chondroitin sulfate and dynamic loading alter chondrogenesis of human MSCs in PEG hydrogels. Biotechnology and Bioengineering, 109(10), 2671–2682.

    CAS  PubMed  Article  Google Scholar 

  165. 165.

    Mangan, B., Hurtig, M. B., & Dickey, J. P. (2010). Application of robotic technology in biomechanics to study joint laxity. Journal of Medical Engineering & Technology, 34(7–8), 399–407.

    CAS  Article  Google Scholar 

  166. 166.

    Poveda Roda, R., Bagán, J. V., Díaz Fernández, J. M., Hernández Bazán, S., & Jiménez Soriano, Y. (2007). Review of temporomandibular joint pathology: part I: classification, epidemiology and risk factors. Medicina Oral, Patología Oral y Cirugía Bucal, 12(4), 292–298.

    Google Scholar 

  167. 167.

    Jeong, S. Y., Kim, D. H., Ha, J., Jin, H. J., Kwon, S. J., Chang, J. W., et al. (2013). Thrombospondin‐2 secreted by human umbilical cord blood‐derived mesenchymal stem cells promotes chondrogenic differentiation. Stem Cells, 31(10), 2136–2148.

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National University Healthcare System, National University of Singapore (R221000067133, R221000070733, R221000077733 and R221000083112) and National Medical Research Council Singapore (R221000080511).

Conflict of interest

The authors declare that there is no conflict of interests regarding the publication of this paper.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Wei Seong Toh.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, S., Yap, A.U.J. & Toh, W.S. Stem Cells for Temporomandibular Joint Repair and Regeneration. Stem Cell Rev and Rep 11, 728–742 (2015). https://doi.org/10.1007/s12015-015-9604-x

Download citation

Keywords

  • Stem cells
  • Secretome
  • Temporomandibular joint
  • Cartilage
  • Tissue engineering
  • Tissue regeneration