Advertisement

Chondrogenesis from Human Mesenchymal Stem Cells: Role of Culture Conditions

  • Jean F. Welter
  • Luis A. Solchaga
  • Harihara Baskaran
Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 5)

Abstract

Tissue engineering has experienced significant advances in recent years. The application of cell-based tissue engineering approaches to articular cartilage repair has been a primary focus because articular cartilage is avascular and without a significant source of reparative cells. With recent advances in MSC biology, cell-based repair or regeneration of articular cartilage is becoming a practical possibility. However, isolation, and chondrogenic differentiation of the MSCs require further optimization.

Three phases are critical for MSC-based cartilage tissue engineering: isolation of the primary cells, mitotic expansion, and chondrogenic differentiation. Multiple variables play significant roles in each of these phases. Media composition, growth factor supplementation, and scaffold effects are just a few examples of the culture-condition variables critical to the success of MSC-based cartilage tissue engineering. These variables and their effects on MSC isolation, expansion, and differentiation will be discussed in this chapter.

Keywords

Tissue Engineering Articular Cartilage Chondrogenic Differentiation Tissue Culture Plastic Scaffold Material 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors wish to acknowledge funding from the National Institutes of Health AR050208 and AR053622. We thank Ms. Kitsie Penick, Ms. Lori Duesler, and Ms. Chih-Ling Chou for technical assistance. We also wish to acknowledge the contributions to the field of MSC chondrogenesis by the hundreds of researchers who could not be cited due to formatting constraints on this chapter.

References

  1. Abrahamsson CK, Yang F, Park H, Brunger JM, Valonen PK, Langer R, Welter JF, Caplan AI, Guilak F, Freed LE (2010) Chondrogenesis and mineralization during in vitro culture of human mesenchymal stem cells on three-dimensional woven scaffolds. Tissue Eng Part A 16:3709–3718PubMedCrossRefGoogle Scholar
  2. Ahmed N, Dreier R, Gopferich A, Grifka J, Grassel S (2007) Soluble signalling factors derived from differentiated cartilage tissue affect chondrogenic differentiation of rat adult marrow stromal cells. Cell Physiol Biochem 20:665–678PubMedGoogle Scholar
  3. Ballock RT, Heydemann A, Wakefield LM, Flanders KC, Roberts AB, Sporn MB (1993) TGF-beta 1 prevents hypertrophy of epiphyseal chondrocytes: regulation of gene expression for cartilage matrix proteins and metalloproteases. Dev Biol 158:414–429PubMedCrossRefGoogle Scholar
  4. Barry F, Boynton RE, Liu B, Murphy JM (2001) Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. Exp Cell Res 268:189–200PubMedCrossRefGoogle Scholar
  5. Caplan AI (1994) The mesengenic process. Clin Plast Surg 21:429–435PubMedGoogle Scholar
  6. Curran JM, Pu F, Chen R, Hunt JA (2011) The use of dynamic surface chemistries to control msc isolation and function. Biomaterials 32:4753–4760PubMedCrossRefGoogle Scholar
  7. DiGirolamo CM, Stokes D, Colter D, Phinney DG, Class R, Prockop DJ (1999) Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol 107:275–281PubMedCrossRefGoogle Scholar
  8. Friedenstein AJ (1976) Precursor cells of mechanocytes. Int Rev Cytol 47:327–359PubMedCrossRefGoogle Scholar
  9. Giovannini S, Diaz-Romero J, Aigner T, Heini P, Mainil-Varlet P, Nesic D (2010) Micromass co-culture of human articular chondrocytes and human bone marrow mesenchymal stem cells to investigate stable neocartilage tissue formation in vitro. Eur Cell Mater 20:245–259PubMedGoogle Scholar
  10. Guilak F, Estes BT, Diekman BO, Moutos FT, Gimble JM (2010) 2010 Nicolas Andry Award: multipotent adult stem cells from adipose tissue for musculoskeletal tissue engineering. Clin Orthop 468:2530–2540PubMedCrossRefGoogle Scholar
  11. Hennig T, Lorenz H, Thiel A, Goetzke K, Dickhut A, Geiger F, Richter W (2007) Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6. J Cell Physiol 211:682–691PubMedCrossRefGoogle Scholar
  12. Holzwarth C, Vaegler M, Gieseke F, Pfister SM, Handgretinger R, Kerst G, Müller I (2010) Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells. BMC Cell Biol 11:11PubMedCrossRefGoogle Scholar
  13. Huang AH, Farrell MJ, Kim M, Mauck RL (2010) Long-term dynamic loading improves the mechanical pro­perties of chondrogenic mesenchymal stem cell-laden hydrogel. Eur Cell Mater 19:72–85PubMedGoogle Scholar
  14. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238:265–272PubMedCrossRefGoogle Scholar
  15. Kolf CM, Cho E, Tuan RS (2007) Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther 9:204PubMedCrossRefGoogle Scholar
  16. Lennon DP, Haynesworth SE, Bruder SP, Jaiswal N, Caplan AI (1996) Human and animal mesenchymal progenitor cells from bone marrow: identification of serum for optimal selection and proliferation. In Vitro Cell Dev Biol 32:602–611CrossRefGoogle Scholar
  17. Longobardi L, O’Rear L, Aakula S, Johnstone B, Shimer K, Chytil A, Horton WA, Moses HL, Spagnoli A (2006) Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling. J Bone Miner Res 21:626–636PubMedCrossRefGoogle Scholar
  18. Manwaring ME, Walsh JF, Tresco PA (2004) Contact guidance induced organization of extracellular matrix. Biomaterials 25:3631–3638PubMedCrossRefGoogle Scholar
  19. Mauck RL, Yuan X, Tuan RS (2006) Chondrogenic differentiation and functional maturation of bovine mesenchymal stem cells in long-term agarose culture. Osteoarthritis Cartilage 14:179–189PubMedCrossRefGoogle Scholar
  20. Mueller MB, Tuan RS (2008) Functional characterization of hypertrophy in chondrogenesis of human mesenchymal stem cells. Arthritis Rheum 58:1377–1388PubMedCrossRefGoogle Scholar
  21. Müller I, Kordowich S, Holzwarth C, Spano C, Isensee G, Staiber A, Viebahn S, Gieseke F, Langer H, Gawaz MP, Horwitz EM, Conte P, Handgretinger R, Dominici M (2006) Animal serum-free culture conditions for isolation and expansion of multipotent mesenchymal stromal cells from human BM. Cytotherapy 8:437–444PubMedCrossRefGoogle Scholar
  22. Owen M (1988) Marrow stromal stem cells. J Cell Sci Suppl 10:63–76PubMedGoogle Scholar
  23. Pelttari K, Winter A, Steck E, Goetzke K, Hennig T, Ochs BG, Aigner T, Richter W (2006) Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum 54:3254–3266PubMedCrossRefGoogle Scholar
  24. Penick KJ, Solchaga LA, Welter JF (2005) High-throughput aggregate culture system to assess the chondrogenic potential of mesenchymal stem cells. Biotechniques 39:687–691PubMedCrossRefGoogle Scholar
  25. Puetzer JL, Petitte JN, Loboa EG (2010) Comparative review of growth factors for induction of three-dimensional in vitro chondrogenesis in human mesenchymal stem cells isolated from bone marrow and adipose tissue. Tissue Eng Part B Rev 16:435–444PubMedCrossRefGoogle Scholar
  26. Shirazi R, Shirazi-Adl A, Hurtig M (2008) Role of cartilage collagen fibrils networks in knee joint biomechanics under compression. J Biomech 41:3340–3348PubMedCrossRefGoogle Scholar
  27. Solchaga LA, Penick K, Porter JD, Goldberg VM, Caplan AI, Welter JF (2005) FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J Cell Physiol 203:398–409PubMedCrossRefGoogle Scholar
  28. Solchaga LA, Penick K, Goldberg VM, Caplan AI, Welter JF (2010) Fibroblast growth factor-2 enhances proliferation and delays loss of chondrogenic potential in human adult bone-marrow-derived mesenchymal stem cells. Tissue Eng Part A 16:1009–1019PubMedCrossRefGoogle Scholar
  29. Solchaga LA, Penick KJ, Welter JF (2011) Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells: tips and tricks. Methods Mol Biol 698:253–278PubMedCrossRefGoogle Scholar
  30. Solorio LD, Fu AS, Hernandez-Irizarry R, Alsberg E (2010) Chondrogenic differentiation of human mesenchymal stem cell aggregates via controlled release of TGF-beta1 from incorporated polymer microspheres. J Biomed Mater Res 92:1139–1144Google Scholar
  31. Solursh M, Linsenmayer TF, Jensen KL (1982) Chondrogenesis from single limb mesenchyme cells. Dev Biol 94:259–264PubMedCrossRefGoogle Scholar
  32. Valonen PK, Moutos FT, Kusanagi A, Moretti MG, Diekman BO, Welter JF, Caplan AI, Guilak F, Freed LE (2010) In vitro generation of mechanically functional cartilage grafts based on adult human stem cells and 3D-woven poly(epsilon-caprolactone) scaffolds. Biomaterials 31:2193–2200PubMedCrossRefGoogle Scholar
  33. Varghese S, Hwang NS, Canver AC, Theprungsirikul P, Lin DW, Elisseeff J (2008) Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells. Matrix Biol 27:12–21PubMedCrossRefGoogle Scholar
  34. Weiss S, Hennig T, Bock R, Steck E, Richter W (2010) Impact of growth factors and PTHrP on early and late chondrogenic differentiation of human mesenchymal stem cells. J Cell Physiol 223:84–93PubMedGoogle Scholar
  35. Worster AA, Brower-Toland BD, Fortier LA, Bent SJ, Williams J, Nixon AJ (2001) Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-beta1 in monolayer and insulin-like growth factor-I in a three-dimensional matrix. J Orthop Res 19:738–749PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Jean F. Welter
    • 1
  • Luis A. Solchaga
    • 2
  • Harihara Baskaran
    • 3
  1. 1.Department of Biology, Skeletal Research CenterCase Western Reserve University, Millis Science CenterClevelandUSA
  2. 2.Principal Scientist, Research and DevelopmentBioMimetic Therapeutics, Inc.FranklinUSA
  3. 3.Department of Chemical Engineering111C A.W.Smith Building, Case Western Reserve UniversityClevelandUSA

Personalised recommendations