Skip to main content
SpringerLink
Log in

Chondrogenic Differentiation of Amniotic Fluid Stem Cells and Their Potential for Regenerative Therapy

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Chronic articular cartilage defects are the most common disabling conditions of humans in the western world. The incidence for cartilage defects is increasing with age and the most prominent risk factors are overweight and sports associated overloading. Damage of articular cartilage frequently leads to osteoarthritis due to the aneural and avascular nature of articular cartilage, which impairs regeneration and repair. Hence, patients affected by cartilage defects will benefit from a cell-based transplantation strategy. Autologous chondrocytes, mesenchymal stem cells and embryonic stem cells are suitable donor cells for regeneration approaches and most recently the discovery of amniotic fluid stem cells has opened a plethora of new therapeutic options. It is the aim of this review to summarize recent advances in the use of amniotic fluid stem cells as novel cell sources for the treatment of articular cartilage defects. Molecular aspects of articular cartilage formation as well as degeneration are summarized and the role of growth factor triggered signaling pathways, scaffolds, hypoxia and autophagy during the process of chondrogenic differentiation are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Nehrer, S., & Minas, T. (2000). Treatment of articular cartilage defects. Investigative Radiology, 35, 639–646.

    Article  PubMed  CAS  Google Scholar 

  2. Jiang, L., Tian, W., Wang, Y., et al. (2011). Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis. Joint Bone Spine.

  3. Jiang, Y. Z., Zhang, S. F., Qi, Y. Y., Wang, L. L., & Ouyang, H. W. (2011). Cell transplantation for articular cartilage defects: principles of past, present, and future practice. Cell Transplantation, 20, 593–607.

    Article  PubMed  Google Scholar 

  4. Bedi, A., Feeley, B. T., & Williams, R. J., 3rd. (2010). Management of articular cartilage defects of the knee. The Journal of Bone and Joint Surgery. American Volume, 92, 994–1009.

    Article  PubMed  Google Scholar 

  5. Nehrer, S., Dorotka, R., Domayer, S., Stelzeneder, D., & Kotz, R. (2009). Treatment of full-thickness chondral defects with hyalograft C in the knee: a prospective clinical case series with 2 to 7 years’ follow-up. The American Journal of Sports Medicine, 37(Suppl 1), 81S–87S.

    Article  PubMed  Google Scholar 

  6. Salzmann, G. M., Sauerschnig, M., Berninger, M. T., et al. (2011). The dependence of autologous chondrocyte transplantation on varying cellular passage, yield and culture duration. Biomaterials, 32, 5810–5818.

    Article  PubMed  CAS  Google Scholar 

  7. Schnabel, M., Marlovits, S., Eckhoff, G., et al. (2002). Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthritis and Cartilage, 10, 62–70.

    Article  PubMed  CAS  Google Scholar 

  8. 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, 2521–2529.

    Article  PubMed  Google Scholar 

  9. Vinardell, T., Buckley, C. T., Thorpe, S. D., & Kelly, D. J. (2011). Composition-function relations of cartilaginous tissues engineered from chondrocytes and mesenchymal stem cells isolated from bone marrow and infrapatellar fat pad. Journal of Tissue Engineering and Regenerative Medicine, 5, 673–683.

    Article  PubMed  CAS  Google Scholar 

  10. Erickson, I. E., Huang, A. H., Chung, C., Li, R. T., Burdick, J. A., & Mauck, R. L. (2009). Differential maturation and structure-function relationships in mesenchymal stem cell- and chondrocyte-seeded hydrogels. Tissue Engineering. Part A, 15, 1041–1052.

    Article  PubMed  CAS  Google Scholar 

  11. De Coppi, P., Bartsch, G., Jr., Siddiqui, M. M., et al. (2007). Isolation of amniotic stem cell lines with potential for therapy. Nature Biotechnology, 25, 100–106.

    Article  PubMed  Google Scholar 

  12. Rosner, M., Dolznig, H., Schipany, K., Mikula, M., Brandau, O., & Hengstschlager, M. (2011). Human amniotic fluid stem cells as a model for functional studies of genes involved in human genetic diseases or oncogenesis. Oncotarget, 2, 705–712.

    PubMed  Google Scholar 

  13. Da Sacco, S., De Filippo, R. E., & Perin, L. (2010). Amniotic fluid as a source of pluripotent and multipotent stem cells for organ regeneration. Current Opinion in Organ Transplantation.

  14. Rosner, M., Schipany, K., Gundacker, C., et al. (2012). Renal differentiation of amniotic fluid stem cells: perspectives for clinical application and for studies on specific human genetic diseases. European Journal of Clinical Investigation, 42, 677–684.

    Article  PubMed  CAS  Google Scholar 

  15. Rosner, M., Mikula, M., Preitschopf, A., Feichtinger, M., Schipany, K., & Hengstschlager, M. (2012). Neurogenic differentiation of amniotic fluid stem cells. Amino Acids, 42, 1591–1596.

    Article  PubMed  CAS  Google Scholar 

  16. Rountree, R. B., Schoor, M., Chen, H., et al. (2004). BMP receptor signaling is required for postnatal maintenance of articular cartilage. PLoS Biology, 2, e355.

    Article  PubMed  Google Scholar 

  17. Francis-West, P. H., Abdelfattah, A., Chen, P., et al. (1999). Mechanisms of GDF-5 action during skeletal development. Development, 126, 1305–1315.

    PubMed  CAS  Google Scholar 

  18. Koyama, E., Shibukawa, Y., Nagayama, M., et al. (2008). A distinct cohort of progenitor cells participates in synovial joint and articular cartilage formation during mouse limb skeletogenesis. Developmental Biology, 316, 62–73.

    Article  PubMed  CAS  Google Scholar 

  19. Pacifici, M., Koyama, E., & Iwamoto, M. (2005). Mechanisms of synovial joint and articular cartilage formation: recent advances, but many lingering mysteries. Birth Defects Research. Part C, Embryo Today, 75, 237–248.

    Article  CAS  Google Scholar 

  20. Brunet, L. J., McMahon, J. A., McMahon, A. P., & Harland, R. M. (1998). Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science, 280, 1455–1457.

    Article  PubMed  CAS  Google Scholar 

  21. Hartmann, C., & Tabin, C. J. (2001). Wnt-14 plays a pivotal role in inducing synovial joint formation in the developing appendicular skeleton. Cell, 104, 341–351.

    Article  PubMed  CAS  Google Scholar 

  22. Iwamoto, M., Higuchi, Y., Koyama, E., et al. (2000). Transcription factor ERG variants and functional diversification of chondrocytes during limb long bone development. The Journal of Cell Biology, 150, 27–40.

    Article  PubMed  CAS  Google Scholar 

  23. Storm, E. E., Huynh, T. V., Copeland, N. G., Jenkins, N. A., Kingsley, D. M., & Lee, S. J. (1994). Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily. Nature, 368, 639–643.

    Article  PubMed  CAS  Google Scholar 

  24. Craig, F. M., Bentley, G., & Archer, C. W. (1987). The spatial and temporal pattern of collagens I and II and keratan sulphate in the developing chick metatarsophalangeal joint. Development, 99, 383–391.

    PubMed  CAS  Google Scholar 

  25. Bell, D. M., Leung, K. K., Wheatley, S. C., et al. (1997). SOX9 directly regulates the type-II collagen gene. Nature Genetics, 16, 174–178.

    Article  PubMed  CAS  Google Scholar 

  26. Kou, I., & Ikegawa, S. (2004). SOX9-dependent and -independent transcriptional regulation of human cartilage link protein. Journal of Biological Chemistry, 279, 50942–50948.

    Article  PubMed  CAS  Google Scholar 

  27. Sekiya, I., Tsuji, K., Koopman, P., et al. (2000). SOX9 enhances aggrecan gene promoter/enhancer activity and is up-regulated by retinoic acid in a cartilage-derived cell line, TC6. Journal of Biological Chemistry, 275, 10738–10744.

    Article  PubMed  CAS  Google Scholar 

  28. Zhang, P., Jimenez, S. A., & Stokes, D. G. (2003). Regulation of human COL9A1 gene expression. Activation of the proximal promoter region by SOX9. Journal of Biological Chemistry, 278, 117–123.

    Article  PubMed  CAS  Google Scholar 

  29. Liu, C. J., Zhang, Y., Xu, K., Parsons, D., Alfonso, D., & Di Cesare, P. E. (2007). Transcriptional activation of cartilage oligomeric matrix protein by Sox9, Sox5, and Sox6 transcription factors and CBP/p300 coactivators. Frontiers in Bioscience, 12, 3899–3910.

    Article  PubMed  CAS  Google Scholar 

  30. Ikeda, T., Kamekura, S., Mabuchi, A., et al. (2004). The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage. Arthritis and Rheumatism, 50, 3561–3573.

    Article  PubMed  CAS  Google Scholar 

  31. Archer, C. W., Dowthwaite, G. P., & Francis-West, P. (2003). Development of synovial joints. Birth Defects Research. Part C, Embryo Today, 69, 144–155.

    Article  CAS  Google Scholar 

  32. Grimshaw, M. J., & Mason, R. M. (2001). Modulation of bovine articular chondrocyte gene expression in vitro by oxygen tension. Osteoarthritis and Cartilage, 9, 357–364.

    Article  PubMed  CAS  Google Scholar 

  33. Buckwalter, J. A. (2002). Articular cartilage injuries. Clinical Orthopaedics and Related Research, (pp. 21–37).

  34. Goldring, M. B., & Goldring, S. R. (2010). Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Annals of the New York Academy of Sciences, 1192, 230–237.

    Article  PubMed  CAS  Google Scholar 

  35. Madry, H., Grun, U. W., & Knutsen, G. (2011). Cartilage repair and joint preservation: medical and surgical treatment options. Deutsches Ärzteblatt International, 108, 669–677.

    PubMed  Google Scholar 

  36. Goldring, M. B., & Goldring, S. R. (2007). Osteoarthritis. Journal of Cellular Physiology, 213, 626–634.

    Article  PubMed  CAS  Google Scholar 

  37. Murphy, G., & Nagase, H. (2008). Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nature Clinical Practice Rheumatology, 4, 128–135.

    Article  PubMed  CAS  Google Scholar 

  38. Goldring, S. R. (2009). Role of bone in osteoarthritis pathogenesis. Medicine Clinics of North America, 93, 25–35. xv.

    Article  Google Scholar 

  39. Schroeppel, J. P., Crist, J. D., Anderson, H. C., & Wang, J. (2011). Molecular regulation of articular chondrocyte function and its significance in osteoarthritis. Histology and Histopathology, 26, 377–394.

    PubMed  CAS  Google Scholar 

  40. Gadjanski, I., Spiller, K., & Vunjak-Novakovic, G. (2011). Time-dependent processes in stem cell-based tissue engineering of articular cartilage. Stem Cell Reviews.

  41. Zhao, Q., Eberspaecher, H., Lefebvre, V., & De Crombrugghe, B. (1997). Parallel expression of Sox9 and Col2a1 in cells undergoing chondrogenesis. Developmental Dynamics, 209, 377–386.

    Article  PubMed  CAS  Google Scholar 

  42. Ng, L. J., Wheatley, S., Muscat, G. E., et al. (1997). SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Developmental Biology, 183, 108–121.

    Article  PubMed  CAS  Google Scholar 

  43. Leung, V. Y., Gao, B., Leung, K. K., et al. (2011). SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression. PLoS Genetics, 7, e1002356.

    Article  PubMed  CAS  Google Scholar 

  44. Roberts, S., Genever, P., McCaskie, A., & De Bari, C. (2011). Prospects of stem cell therapy in osteoarthritis. Regenerative Medicine, 6, 351–366.

    Article  PubMed  Google Scholar 

  45. 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, 7, 544–559.

    Article  PubMed  Google Scholar 

  46. Pittenger, M. F., Mackay, A. M., Beck, S. C., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143–147.

    Article  PubMed  CAS  Google Scholar 

  47. Liu, T. M., Martina, M., Hutmacher, D. W., Hui, J. H., Lee, E. H., & Lim, B. (2007). Identification of common pathways mediating differentiation of bone marrow- and adipose tissue-derived human mesenchymal stem cells into three mesenchymal lineages. Stem Cells, 25, 750–760.

    Article  PubMed  Google Scholar 

  48. Kaviani, A., Perry, T. E., Dzakovic, A., Jennings, R. W., Ziegler, M. M., & Fauza, D. O. (2001). The amniotic fluid as a source of cells for fetal tissue engineering. Journal of Pediatric Surgery, 36, 1662–1665.

    Article  PubMed  CAS  Google Scholar 

  49. Prusa, A. R., Marton, E., Rosner, M., Bernaschek, G., & Hengstschlager, M. (2003). Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research? Human Reproduction, 18, 1489–1493.

    Article  PubMed  Google Scholar 

  50. In’t Anker, P. S., Scherjon, S. A., Kleijburg-van der Keur, C., et al. (2003). Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood, 102, 1548–1549.

    Article  Google Scholar 

  51. Miranda-Sayago, J. M., Fernandez-Arcas, N., Benito, C., Reyes-Engel, A., Carrera, J., & Alonso, A. (2011). Lifespan of human amniotic fluid-derived multipotent mesenchymal stromal cells. Cytotherapy, 13, 572–581.

    Article  PubMed  CAS  Google Scholar 

  52. Kim, K., Doi, A., Wen, B., et al. (2010). Epigenetic memory in induced pluripotent stem cells. Nature, 467, 285–290.

    Article  PubMed  CAS  Google Scholar 

  53. Moschidou, D., Mukherjee, S., Blundell, M. P., et al. (2012). Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach. Molecular Therapy.

  54. Tsai, M. S., Lee, J. L., Chang, Y. J., & Hwang, S. M. (2004). Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Human Reproduction, 19, 1450–1456.

    Article  PubMed  Google Scholar 

  55. Siegel, N., Rosner, M., Unbekandt, M., et al. (2010). Contribution of human amniotic fluid stem cells to renal tissue formation depends on mTOR. Human Molecular Genetics, 19, 3320–3331.

    Article  PubMed  CAS  Google Scholar 

  56. Valli, A., Rosner, M., Fuchs, C., et al. (2010). Embryoid body formation of human amniotic fluid stem cells depends on mTOR. Oncogene, 29, 966–977.

    Article  PubMed  CAS  Google Scholar 

  57. Rosner, M., Siegel, N., Fuchs, C., Slabina, N., Dolznig, H., & Hengstschlager, M. (2010). Efficient siRNA-mediated prolonged gene silencing in human amniotic fluid stem cells. Nature Protocols, 5, 1081–1095.

    Article  PubMed  CAS  Google Scholar 

  58. Kunisaki, S. M., Jennings, R. W., & Fauza, D. O. (2006). Fetal cartilage engineering from amniotic mesenchymal progenitor cells. Stem Cells and Development, 15, 245–253.

    Article  PubMed  CAS  Google Scholar 

  59. Kim, J., Lee, Y., Kim, H., et al. (2007). Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells. Cell Proliferation, 40, 75–90.

    Article  PubMed  CAS  Google Scholar 

  60. Kolambkar, Y. M., Peister, A., Soker, S., Atala, A., & Guldberg, R. E. (2007). Chondrogenic differentiation of amniotic fluid-derived stem cells. Journal of Molecular Histology, 38, 405–413.

    Article  PubMed  CAS  Google Scholar 

  61. Arnhold, S., Gluer, S., Hartmann, K., et al. (2011). Amniotic-fluid stem cells: growth dynamics and differentiation potential after a CD-117-based selection procedure. Stem Cells International, 2011, 715341.

    Article  PubMed  CAS  Google Scholar 

  62. Park, J. S., Shim, M. S., Shim, S. H., et al. (2011). Chondrogenic potential of stem cells derived from amniotic fluid, adipose tissue, or bone marrow encapsulated in fibrin gels containing TGF-beta3. Biomaterials, 32, 8139–8149.

    Article  PubMed  CAS  Google Scholar 

  63. Merino, R., Macias, D., Ganan, Y., et al. (1999). Expression and function of Gdf-5 during digit skeletogenesis in the embryonic chick leg bud. Developmental Biology, 206, 33–45.

    Article  PubMed  CAS  Google Scholar 

  64. Storm, E. E., & Kingsley, D. M. (1999). GDF5 coordinates bone and joint formation during digit development. Developmental Biology, 209, 11–27.

    Article  PubMed  CAS  Google Scholar 

  65. Narcisi, R., Quarto, R., Ulivi, V., Muraglia, A., Molfetta, L., & Giannoni, P. (2012). TGF beta-1 administration during ex vivo expansion of human articular chondrocytes in a serum-free medium redirects the cell phenotype toward hypertrophy. Journal of Cellular Physiology, 227, 3282–3290.

    Article  PubMed  CAS  Google Scholar 

  66. Guo, X., Day, T. F., Jiang, X., Garrett-Beal, L., Topol, L., & Yang, Y. (2004). Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation. Genes & Development, 18, 2404–2417.

    Article  CAS  Google Scholar 

  67. Day, T. F., Guo, X., Garrett-Beal, L., & Yang, Y. (2005). Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Developmental Cell, 8, 739–750.

    Article  PubMed  CAS  Google Scholar 

  68. Yang, Z., Zou, Y., Guo, X. M., et al. (2012). Temporal activation of beta-catenin signaling in the chondrogenic process of mesenchymal stem cells affects the phenotype of the cartilage generated. Stem Cells and Development.

  69. Saito, T., Ikeda, T., Nakamura, K., Chung, U. I., & Kawaguchi, H. (2007). S100A1 and S100B, transcriptional targets of SOX trio, inhibit terminal differentiation of chondrocytes. EMBO Reports, 8, 504–509.

    Article  PubMed  CAS  Google Scholar 

  70. Yamashita, S., Andoh, M., Ueno-Kudoh, H., Sato, T., Miyaki, S., & Asahara, H. (2009). Sox9 directly promotes Bapx1 gene expression to repress Runx2 in chondrocytes. Experimental Cell Research, 315, 2231–2240.

    Article  PubMed  CAS  Google Scholar 

  71. Higashikawa, A., Saito, T., Ikeda, T., et al. (2009). Identification of the core element responsive to runt-related transcription factor 2 in the promoter of human type X collagen gene. Arthritis and Rheumatism, 60, 166–178.

    Article  PubMed  CAS  Google Scholar 

  72. Soung do, Y., Dong, Y., Wang, Y., et al. (2007). Runx3/AML2/Cbfa3 regulates early and late chondrocyte differentiation. Journal of Bone and Mineral Research, 22, 1260–1270.

    Article  PubMed  CAS  Google Scholar 

  73. Mengshol, J. A., Vincenti, M. P., & Brinckerhoff, C. E. (2001). IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. Nucleic Acids Research, 29, 4361–4372.

    Article  PubMed  CAS  Google Scholar 

  74. Kunisaki, S. M., Fuchs, J. R., Steigman, S. A., & Fauza, D. O. (2007). A comparative analysis of cartilage engineered from different perinatal mesenchymal progenitor cells. Tissue Engineering, 13, 2633–2644.

    Article  PubMed  CAS  Google Scholar 

  75. Khan, W. S., Adesida, A. B., Tew, S. R., Lowe, E. T., & Hardingham, T. E. (2010). Bone marrow-derived mesenchymal stem cells express the pericyte marker 3 G5 in culture and show enhanced chondrogenesis in hypoxic conditions. Journal of Orthopaedic Research, 28, 834–840.

    PubMed  CAS  Google Scholar 

  76. Kay, A., Richardson, J., & Forsyth, N. R. (2011). Physiological normoxia and chondrogenic potential of chondrocytes. Frontiers in Bioscience (Elite Edition), 3, 1365–1374.

    Google Scholar 

  77. Zelzer, E., Amarilio, R., Viukov, S. V., Sharir, A., Eshkar-Oren, I., & Johnson, R. S. (2007). HIF1 alpha regulation of Sox9 is necessary to maintain differentiation of hypoxic prechondrogenic cells during early skeletogenesis. Development, 134, 3917–3928.

    Article  PubMed  Google Scholar 

  78. Murphy, C. L., Lafont, J. E., & Talma, S. (2007). Hypoxia-inducible factor 2 alpha is essential for hypoxic induction of the human articular chondrocyte phenotype. Arthritis and Rheumatism, 56, 3297–3306.

    Article  PubMed  Google Scholar 

  79. Hashimoto, S., Creighton-Achermann, L., Takahashi, K., Amiel, D., Coutts, R. D., & Lotz, M. (2002). Development and regulation of osteophyte formation during experimental osteoarthritis. Osteoarthritis and Cartilage, 10, 180–187.

    Article  PubMed  CAS  Google Scholar 

  80. Yang, D. C., Yang, M. H., Tsai, C. C., Huang, T. F., Chen, Y. H., & Hung, S. C. (2011). Hypoxia inhibits osteogenesis in human mesenchymal stem cells through direct regulation of RUNX2 by TWIST. PLoS One, 6, e23965.

    Article  PubMed  CAS  Google Scholar 

  81. Lotz, M. K., & Carames, B. (2011). Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA. Nature Reviews. Rheumatology, 7, 579–587.

    PubMed  CAS  Google Scholar 

  82. Carames, B., Taniguchi, N., Otsuki, S., Blanco, F. J., & Lotz, M. (2010). Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis and Rheumatism, 62, 791–801.

    Article  PubMed  CAS  Google Scholar 

  83. Carames, B., Hasegawa, A., Taniguchi, N., Miyaki, S., Blanco, F. J., & Lotz, M. (2012). Autophagy activation by rapamycin reduces severity of experimental osteoarthritis. Annals of the Rheumatic Diseases, 71, 575–581.

    Article  PubMed  CAS  Google Scholar 

  84. Shigemitsu, K., Tsujishita, Y., Hara, K., Nanahoshi, M., Avruch, J., Yonezawa, K., & Yonezawa, K. (1999). Regulation of translational effectors by amino acid and mammalian target of rapamycin signaling pathways. Possible involvement of autophagy in cultured hepatoma cells. Journal of Biological Chemistry, 274, 1058–1065.

    Article  PubMed  CAS  Google Scholar 

  85. Toschi, A., Lee, E., Gadir, N., Ohh, M., & Foster, D. A. (2008). Differential dependence of hypoxia-inducible factors 1 alpha and 2 alpha on mTORC1 and mTORC2. Journal of Biological Chemistry, 283, 34495–34499.

    Article  PubMed  CAS  Google Scholar 

  86. Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011). mTOR: from growth signal integration to cancer, diabetes and ageing. Nature Reviews Molecular Cell Biology, 12, 21–35.

    Article  PubMed  CAS  Google Scholar 

  87. Phornphutkul, C., Wu, K. Y., Auyeung, V., Chen, Q., & Gruppuso, P. A. (2008). mTOR signaling contributes to chondrocyte differentiation. Developmental Dynamics, 237, 702–712.

    Article  PubMed  CAS  Google Scholar 

  88. Qureshi, H. Y., Ahmad, R., Sylvester, J., & Zafarullah, M. (2007). Requirement of phosphatidylinositol 3-kinase/Akt signaling pathway for regulation of tissue inhibitor of metalloproteinases-3 gene expression by TGF-beta in human chondrocytes. Cellular Signalling, 19, 1643–1651.

    Article  PubMed  CAS  Google Scholar 

  89. Starkman, B. G., Cravero, J. D., Delcarlo, M., & Loeser, R. F. (2005). IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK. Biochemistry Journal, 389, 723–729.

    Article  CAS  Google Scholar 

Download references

Conflicts of interest

The authors declare no potential conflicts of interest.

Author information

Authors and Affiliations

  1. Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria

    Andrea Preitschopf, Kongzhao Li, Margit Rosner, Markus Hengstschläger & Mario Mikula

  2. Center for Regenerative Medicine, Danube University Krems, Krems, Austria

    Hannes Zwickl

  3. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria

    Kongzhao Li & Gert Lubec

  4. 1st Department of Obstetrics and Gynaecology, Semmelweis University Medical School, Baross utca 27, Budapest, 1088, Hungary

    Gabor Joo

Authors
  1. Andrea Preitschopf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hannes Zwickl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kongzhao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gert Lubec
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gabor Joo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Margit Rosner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Markus Hengstschläger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mario Mikula
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario Mikula.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Preitschopf, A., Zwickl, H., Li, K. et al. Chondrogenic Differentiation of Amniotic Fluid Stem Cells and Their Potential for Regenerative Therapy. Stem Cell Rev and Rep 8, 1267–1274 (2012). https://doi.org/10.1007/s12015-012-9405-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-012-9405-4

Keywords

Search

Navigation