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Top) Alcian Blue staining of constructs seeded with bovine chondrocytes or MSCs in chondrogenic medium with TGF-ß3 (CM+, day 14). Bottom) Compressive Young's modulus of constructs on day 28. *p<0.001 vs. CM- and BM; **p<0.05 vs. chond, n=3.
McKay Orthopaedic Research Laboratory > Mauck Lab > Mesenchymal Stem Cells and Cartilage Tissue Engineering

Mesenchymal Stem Cells and Cartilage Tissue Engineering

The high prevalence of osteoarthritis (OA) [5,6] and the poor intrinsic healing capacity of articular cartilage engender a demand for cell-based strategies for cartilage repair. Consequently, studies have attempted to engineer cartilage via the combination of biodegradable or biocompatible scaffolds with differentiated chondrocytes (e.g., [4,7-9,11,14,15,18,19]). While instrumental for these studies, it is unlikely that a sufficient supply of differentiated cells will be available for clinical applications [3,13]. Mesenchymal stem cells (MSCs) may prove to be a useful alternative, as they retain their chondrogenic differentiation capacity through multiple passages in culture [2,16,17]. While MSCs have been shown to undergo chondrogenic differentiation in a variety of tissue culture systems, few studies have assessed the mechanical integrity of the matrix formed by these newly differentiated cells [4]. Furthermore, the efficacy of these cells in forming a functional matrix must be compared directly to healthy chondrocytes for a proper comparison to be made. Successful replacements for articular cartilage using tissue engineered constructs will require grown tissue possessing functional mechanical properties similar to the native tissue [1,10,12]. This aim of this project is to determine if MSCs seeded in hydrogel constructs exposed to a chondrogenic medium will differentiate and increase in mechanical properties at the same rate as those seeded with chondrocytes. It is hypothesized that increases in mechanical properties of MSC-laden gels will correlate positively with the initial cell seeding density and culture duration and depend on the hydrogel in which they are seeded. This project will define the optimal conditions through which functional articular cartilage replacements may be engineered for clinical applications.

References
  1. Butler DL, Goldstein SA, Guilak F, 2000, "Functional tissue engineering: the role of biomechanics," J Biomech Eng, 122: 570-5.
  2. Caplan AI, 1991, "Mesenchymal stem cells," J Orthop Res, 9: 641-50.
  3. Carver SE, Heath CA, 1999, "Influence of intermittent pressure, fluid flow, and mixing on the regenerative properties of articular chondrocytes," Biotechnol Bioeng, 65: 274-81.
  4. Chang SC, Rowley JA, Tobias G, Genes NG, Roy AK, Mooney DJ, Vacanti CA, Bonassar LJ, 2001, "Injection molding of chondrocyte/alginate constructs in the shape of facial implants," J Biomed Mater Res, 55: 503-11.
  5. Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF, 2000, "Osteoarthritis: new insights. Part 1: the disease and its risk factors," Ann Intern Med, 133: 635-46.
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  7. Freed LE, Marquis JC, Nohria A, Emmanual J, Mikos AG, Langer R, 1993, "Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers," J Biomed Mater Res, 27: 11-23.
  8. Freed LE, Marquis JC, Vunjak-Novakovic G, Emmanual J, Langer R, 1994, "Composition of cell-polymer cartilage implants," Biotech. Bioeng., 43: 605-14.
  9. Freed LE, Martin I, Vunjak-Novakovic G, 1999, "Frontiers in tissue engineering. In vitro modulation of chondrogenesis," Clin Orthop, S46-58.
  10. Garrett JC, 1998, "Osteochonral allografts for reconstruction of articular defects of the knee," Instr Course Lect, 47: 517-22.
  11. Gooch KJ, Kwon JH, Blunk T, Langer R, Freed LE, Vunjak-Novakovic G, 2001, "Effects of mixing intensity on tissue-engineered cartilage," Biotechnol Bioeng, 72: 402-7.
  12. Guilak F, Butler DL, Goldstein SA, 2001, "Functional tissue engineering: the role of biomechanics in articular cartilage repair," Clin Orthop, S295-305.
  13. Lee CR, Grodzinsky AJ, Hsu HP, Martin SD, Spector M, 2000, "Effects of harvest and selected cartilage repair procedures on the physical and biochemical properties of articular cartilage in the canine knee," J Orthop Res, 18: 790-9.
  14. Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK, 2002, "Electrospun nanofibrous structure: a novel scaffold for tissue engineering," J Biomed Mater Res, 60: 613-21.
  15. Martin I, Obradovic B, Treppo S, Grodzinsky AJ, Langer R, Freed LE, Vunjak-Novakovic G, 2000, "Modulation of the mechanical properties of tissue engineered cartilage," Biorheology, 37: 141-7.
  16. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR, 1999, "Multilineage potential of adult human mesenchymal stem cells," Science, 284: 143-7.
  17. Prockop DJ, 1997, "Marrow stromal cells as stem cells for nonhematopoietic tissues," Science, 276: 71-4.
  18. Vunjak-Novakovic G, Obradovic B, Martin I, Bursac PM, Langer R, Freed LE, 1998, "Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering," Biotechnol Prog, 14: 193-202.
  19. Vunjak-Novakovic G, Obradovic B, Martin I, Freed LE, 2002, "Bioreactor studies of native and tissue engineered cartilage," Biorheology, 39: 259-68.

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