Advertisement

Annals of Biomedical Engineering

, Volume 38, Issue 4, pp 1647–1654 | Cite as

IGF-1 and BMP-2 Induces Differentiation of Adipose-Derived Mesenchymal Stem Cells into Chondrocytes-Like Cells

  • Chunhou AnEmail author
  • Yang Cheng
  • Quan Yuan
  • Jianjun Li
Article

Abstract

Articular cartilage defects are common, causing significant morbidities. Tissue engineering using pluripotent stem cells is a new promising modality for cartilage repair. In the current study, we investigated the chondrogenesis of rabbit adipose-derived stem cells (ADSCs). We isolated rabbit ADSCs and transfected these cells with constructs encoding human insulin growth like factor 1 (IGF-1) and bone morphogenic protein 2 (BMP-2). We examined the growth and morphology of these transfected cells and their production of type II collagen and MMP-3. We found that IGF-1 and BMP-2 drove the chondrogenesis of ADSCs, which showed mature chondrocyte-like cells and formed cartilage nodules. These cells also produced type II collagen with a reduced production of MMP-3. Our findings suggested that human ADSCs could differentiate into chondrocyte-like cells driven by IGF-1 and BMP-2 and held promises as an abundant and ready source of stem cells for cartilage repair and regeneration.

Keywords

Stem cells Cartilage regeneration IGF-1 BMP-2 

References

  1. 1.
    Alhadlaq, A., J. H. Elisseeff, L. Hong, C. G. Williams, A. I. Caplan, B. Sharma, R. A. Kopher, S. Tomkoria, D. P. Lennon, and A. Lopez. Adult stem cell driven genesis of human-shaped articular condyle. Ann. Biomed. Eng. 32(7):911–923, 2004.CrossRefPubMedGoogle Scholar
  2. 2.
    Banfi, A., G. Bianchi, R. Notaro, L. Luzzatto, R. Cancedda, and R. Quarto. Replicative aging and gene expression in long-term cultures of human bone marrow stromal cells. Tissue. Eng. 8(6):901–910, 2002.CrossRefPubMedGoogle Scholar
  3. 3.
    Bhosale, A. M., and J. B. Richardson. Articular cartilage: structure, injuries and review of management. Br. Med. Bull. 87:77–95, 2008.CrossRefPubMedGoogle Scholar
  4. 4.
    Cui, B., S. P. Johnson, N.H. Bullock, F. Ali-Osman, D.D. Bigner, and H.S. Friedman. Bifunctional DNA alkylator 1,3-bis(2-chloroethyl)-1-nitrosourea activates the ATR-Chk1 pathway independently of the mismatch repair pathway. Mol. Pharmacol. 2009.Google Scholar
  5. 5.
    De Ugarte, D. A., K. Morizono, A. Elbarbary, Z. Alfonso, P. A. Zuk, M. Zhu, J. L. Dragoo, P. Ashjian, B. Thomas, and P. Benhaim. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 174(3):101–109, 2003.CrossRefPubMedGoogle Scholar
  6. 6.
    Delany, A. M., S. Rydziel, and E. Canalis. Autocrine down-regulation of collagenase-3 in rat bone cell cultures by insulin-like growth factors. Endocrinology 137(11):4665–4670, 1996.CrossRefPubMedGoogle Scholar
  7. 7.
    Dell’Accio, F., C. De Bari, N. M. El Tawil, F. Barone, T. A. Mitsiadis, J. O’Dowd, and C. Pitzalis. Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury. Arthritis Res. Ther. 8(5):R139, 2006.CrossRefPubMedGoogle Scholar
  8. 8.
    Erickson, G. R., J. M. Gimble, D. M. Franklin, H. E. Rice, H. Awad, and F. Guilak. Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. Biochem. Biophys. Res. Commun. 290(2):763–769, 2002.CrossRefPubMedGoogle Scholar
  9. 9.
    Fraser, J. K., I. Wulur, Z. Alfonso, and M. H. Hedrick. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol. 24(4):150–154, 2006.CrossRefPubMedGoogle Scholar
  10. 10.
    Fukumoto, T., J. W. Sperling, A. Sanyal, J. S. Fitzsimmons, G. G. Reinholz, C. A. Conover, and S. W. O’Driscoll. Combined effects of insulin-like growth factor-1 and transforming growth factor-beta1 on periosteal mesenchymal cells during chondrogenesis in vitro. Osteoarthr. Cartil. 11(1):55–64, 2003.CrossRefPubMedGoogle Scholar
  11. 11.
    Gelse, K., C. Muhle, K. Knaup, B. Swoboda, M. Wiesener, F. Hennig, A. Olk, and H. Schneider. Chondrogenic differentiation of growth factor-stimulated precursor cells in cartilage repair tissue is associated with increased HIF-1alpha activity. Osteoarthr. Cartil. 16(12):1457–1465, 2008.CrossRefPubMedGoogle Scholar
  12. 12.
    Guilak, F., H. A. Awad, B. Fermor, H. A. Leddy, and J. M. Gimble. Adipose-derived adult stem cells for cartilage tissue engineering. Biorheology 41(3–4):389–399, 2004.PubMedGoogle Scholar
  13. 13.
    Guilak, F., K. E. Lott, H. A. Awad, Q. Cao, K. C. Hicok, B. Fermor, and J. M. Gimble. Clonal analysis of the differentiation potential of human adipose-derived adult stem cells. J. Cell. Physiol. 206(1):229–237, 2006.CrossRefPubMedGoogle Scholar
  14. 14.
    Hicok, K. C., T. V. Du Laney, Y. S. Zhou, Y. D. Halvorsen, D. C. Hitt, L. F. Cooper, and J. M. Gimble. Human adipose-derived adult stem cells produce osteoid in vivo. Tissue. Eng. 10(3–4):371–380, 2004.CrossRefPubMedGoogle Scholar
  15. 15.
    Huang, J. I., P. A. Zuk, N. F. Jones, M. Zhu, H. P. Lorenz, M. H. Hedrick, and P. Benhaim. Chondrogenic potential of multipotential cells from human adipose tissue. Plast. Reconstr. Surg. 113(2):585–594, 2004.CrossRefPubMedGoogle Scholar
  16. 16.
    Hubbell, J. A. Materials as morphogenetic guides in tissue engineering. Curr. Opin. Biotechnol. 14(5):551–558, 2003.CrossRefPubMedGoogle Scholar
  17. 17.
    Hunziker, E. B. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr. Cartil. 10(6):432–463, 2002.CrossRefPubMedGoogle Scholar
  18. 18.
    Jin, E. J., S. Y. Lee, Y. A. Choi, J. C. Jung, O. S. Bang, and S. S. Kang. BMP-2-enhanced chondrogenesis involves p38 MAPK-mediated down-regulation of Wnt-7a pathway. Mol. Cells 22(3):353–359, 2006.PubMedGoogle Scholar
  19. 19.
    Kern, S., H. Eichler, J. Stoeve, H. Kluter, and K. Bieback. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24(5):1294–1301, 2006.CrossRefPubMedGoogle Scholar
  20. 20.
    Kessler, M. W., G. Ackerman, J. S. Dines, and D. Grande. Emerging technologies and fourth generation issues in cartilage repair. Sports Med. Arthrosc. 16(4):246–254, 2008.CrossRefPubMedGoogle Scholar
  21. 21.
    Knippenberg, M., M. N. Helder, B. Zandieh Doulabi, P. I. Wuisman, and J. Klein-Nulend. Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells. Biochem. Biophys. Res. Commun. 342(3):902–908, 2006.CrossRefPubMedGoogle Scholar
  22. 22.
    Loeser, R. F., C. A. Pacione, and S. Chubinskaya. The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes. Arthritis Rheum. 48(8):2188–2196, 2003.CrossRefPubMedGoogle Scholar
  23. 23.
    Madry, H., G. Kaul, M. Cucchiarini, U. Stein, D. Zurakowski, K. Remberger, M. D. Menger, D. Kohn, and S. B. Trippel. Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I). Gene Ther. 12(15):1171–1179, 2005.CrossRefPubMedGoogle Scholar
  24. 24.
    Martin, I., V. P. Shastri, R. F. Padera, J. Yang, A. J. Mackay, R. Langer, G. Vunjak-Novakovic, and L. E. Freed. Selective differentiation of mammalian bone marrow stromal cells cultured on three-dimensional polymer foams. J. Biomed. Mater. Res. 55(2):229–235, 2001.CrossRefPubMedGoogle Scholar
  25. 25.
    Nakae, J., Y. Kido, and D. Accili. Distinct and overlapping functions of insulin and IGF-I receptors. Endocr. Rev. 22(6):818–835, 2001.CrossRefPubMedGoogle Scholar
  26. 26.
    Nixon, A. J., L. R. Goodrich, M. S. Scimeca, T. H. Witte, L. V. Schnabel, A. E. Watts, and P. D. Robbins. Gene therapy in musculoskeletal repair. Ann. NY Acad. Sci. 1117:310–327, 2007.CrossRefPubMedGoogle Scholar
  27. 27.
    Oh, C. D., and J. S. Chun. Signaling mechanisms leading to the regulation of differentiation and apoptosis of articular chondrocytes by insulin-like growth factor-1. J. Biol. Chem. 278(38):36563–36571, 2003.CrossRefPubMedGoogle Scholar
  28. 28.
    Park, J., K. Gelse, S. Frank, K. von der Mark, T. Aigner, and H. Schneider. Transgene-activated mesenchymal cells for articular cartilage repair: a comparison of primary bone marrow-, perichondrium/periosteum- and fat-derived cells. J. Gene Med. 8(1):112–125, 2006.CrossRefPubMedGoogle Scholar
  29. 29.
    Presta, M., P. Dell’Era, S. Mitola, E. Moroni, R. Ronca, and M. Rusnati. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 16(2):159–178, 2005.CrossRefPubMedGoogle Scholar
  30. 30.
    Ridgway, D. M., S. A. White, M. L. Nicholson, and R. M. Kimber. Pancreatic islet cell transplantation: progress in the clinical setting. Treat. Endocrinol. 2(3):173–189, 2003.CrossRefPubMedGoogle Scholar
  31. 31.
    Rumalla, V. K., and G. L. Borah. Cytokines, growth factors, and plastic surgery. Plast. Reconstr. Surg. 108(3):719–733, 2001.CrossRefPubMedGoogle Scholar
  32. 32.
    Schmidt, M. B., E. H. Chen, and S. E. Lynch. A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair. Osteoarthr. Cartil. 14(5):403–412, 2006.CrossRefPubMedGoogle Scholar
  33. 33.
    Schmitt, B., J. Ringe, T. Haupl, M. Notter, R. Manz, G. R. Burmester, M. Sittinger, and C. Kaps. BMP2 initiates chondrogenic lineage development of adult human mesenchymal stem cells in high-density culture. Differentiation 71(9–10):567–577, 2003.CrossRefPubMedGoogle Scholar
  34. 34.
    Schreml, S., P. Babilas, S. Fruth, E. Orsó, G. Schmitz, M. B. Mueller, M. Nerlich, and L. Prantl. Harvesting human adipose tissue-derived adult stem cells: resection versus liposuction. Cytotherapy 11(7):947–957, 2009.CrossRefPubMedGoogle Scholar
  35. 35.
    Smith, Jr., G. N. The role of collagenolytic matrix metalloproteinases in the loss of articular cartilage in osteoarthritis. Front. Biosci. 11:3081–3095, 2006.CrossRefPubMedGoogle Scholar
  36. 36.
    Sobajima, S., A. L. Shimer, R. C. Chadderdon, J. F. Kompel, J. S. Kim, L. G. Gilbertson, and J. D. Kang. Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction. Spine J. 5(1):14–23, 2005.CrossRefPubMedGoogle Scholar
  37. 37.
    Starkman, B. G., J. D. Cravero, M. Delcarlo, and R. F. Loeser. IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK. Biochem. J. 723–729, 2005.Google Scholar
  38. 38.
    Stenderup, K., J. Justesen, C. Clausen, and M. Kassem. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33(6):919–926, 2003.CrossRefPubMedGoogle Scholar
  39. 39.
    Suzuki, T., K. Bessho, K. Fujimura, Y. Okubo, N. Segami, and T. Iizuka. Regeneration of defects in the articular cartilage in rabbit temporomandibular joints by bone morphogenetic protein-2. Br. J. Oral Maxillofac. Surg. 40(3):201–216, 2002.CrossRefPubMedGoogle Scholar
  40. 40.
    Toh, W. S., Z. Yang, H. Liu, B. C. Heng, E. H. Lee, and T. Cao. Effects of culture conditions and bone morphogenetic protein 2 on extent of chondrogenesis from human embryonic stem cells. Stem Cells 25(4):950–960, 2007.CrossRefPubMedGoogle Scholar
  41. 41.
    Tyler, J. A. Insulin-like growth factor 1 can decrease degradation and promote synthesis of proteoglycan in cartilage exposed to cytokines. Biochem. J. 260(2):543–548, 1989.PubMedGoogle Scholar
  42. 42.
    Wagner, W., F. Wein, A. Seckinger, M. Frankhauser, U. Wirkner, U. Krause, J. Blake, C. Schwager, V. Eckstein, and W. Ansorge. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp. Hematol. 33(11):1402–1416, 2005.CrossRefPubMedGoogle Scholar
  43. 43.
    Wei, Y., Y. Hu, R. Lv, and D. Li. Regulation of adipose-derived adult stem cells differentiating into chondrocytes with the use of rhBMP-2. Cytotherapy 8(6):570–579, 2006.CrossRefPubMedGoogle Scholar
  44. 44.
    Zuk, P. A., M. Zhu, P. Ashjian, D. A. De Ugarte, J. I. Huang, H. Mizuno, Z. C. Alfonso, J. K. Fraser, P. Benhaim, and M. H. Hedrick. Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13(12):4279–4295, 2002.CrossRefPubMedGoogle Scholar
  45. 45.
    Zuk, P. A., M. Zhu, H. Mizuno, J. Huang, J. W. Futrell, A. J. Katz, P. Benhaim, H. P. Lorenz, and M. H. Hedrick. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7(2):211–228, 2001.CrossRefPubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2010

Authors and Affiliations

  1. 1.Department of Orthopedics, Shengjing HospitalChina Medical UniversityShenyangChina

Personalised recommendations