Articular cartilage (AC) is a highly organized connective tissue lining, covering the ends of bones within articulating joints. Its highly ordered structure is essential for stable motion and provides a frictionless surface easing load transfer. AC is vulnerable to lesions and, because it is aneural and avascular, it has limited self-repair potential which often leads to osteoarthritis. To date, no fully successful treatment for osteoarthritis has been reported. Thus, the development of innovative therapeutic approaches is desperately needed. Autologous chondrocyte implantation, the only cell-based surgical intervention approved in the United States for treating cartilage defects, has limitations because of de-differentiation of articular chondrocytes (AChs) upon in vitro expansion. De-differentiation can be abated if initial populations of AChs are co-cultured with mesenchymal stem cells (MSCs), which not only undergo chondrogenesis themselves but also support chondrocyte vitality. In this review we summarize studies utilizing AChs, non-AChs, and MSCs and compare associated outcomes. Moreover, a comprehensive set of recent human studies using chondrocytes to direct MSC differentiation, MSCs to support chondrocyte re-differentiation and proliferation in co-culture environments, and exploratory animal intra- and inter-species studies are systematically reviewed and discussed in an innovative manner allowing side-by-side comparisons of protocols and outcomes. Finally, a comprehensive set of recommendations are made for future studies.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Autologous bone marrow derived mesenchymal stem cell transplantation
Autologous chondrocyte implantation
Articular cartilage tissue engineering
Adipose derived mesenchymal stem cell
Adipose mesenchymal stem cell transplantation
Bone morphogenic protein
Bone marrow derived mesenchymal stem cell
Col I/III-covered ACI
Cartilage oligomeric matrix protein
Fibroblast growth factor
Green fluorescent protein
Insulin like growth factor
Induced MSC w/specified GFs
Mesenchymal stem cell
Parathyroid hormone related peptide
Quantitative polymerase chain reaction
Quantitative reverse transcription polymerase chain reaction
Real time polymerase chain reaction
Severe combined immunodeficiency
Transforming growth factor
Tissue inhibitor metallopeptidase
United State Food & Drug Administration
Acharya, C., A. Adesida, P. Zajac, M. Mumme, J. Riesle, I. Martin, and A. Barbero. Enhanced chondrocyte proliferation and mesenchymal stromal cells chondrogenesis in coculture pellets mediate improved cartilage formation. J. Cell. Physiol. 227:88–97, 2012.
Adesida, A. B., A. Mulet-Sierra, and N. M. Jomha. Hypoxia mediated isolation and expansion enhances the chondrogenic capacity of bone marrow mesenchymal stromal cells. Stem Cell Res. Ther. 3:9, 2012.
Afizah, H., Z. Yang, J. H. Hui, H. W. Ouyang, and E. H. Lee. A comparison between the chondrogenic potential of human bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs) taken from the same donors. Tissue Eng. 13:659–666, 2007.
Ahmed, N., R. Dreier, A. Gopferich, J. Grifka, and S. Grassel. Soluble signalling factors derived from differentiated cartilage tissue affect chondrogenic differentiation of rat adult marrow stromal cells. Cell Physiol. Biochem. 20:665–678, 2007.
Alsalameh, S., R. Amin, T. Gemba, and M. Lotz. Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage. Arthritis Rheum. 50:1522–1532, 2004.
Angele, P., J. U. Yoo, C. Smith, J. Mansour, K. J. Jepsen, M. Nerlich, and B. Johnstone. Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J. Orthop. Res. 21:451–457, 2003.
Arufe, M. C., A. De la Fuente, I. Fuentes, F. J. De Toro, and F. J. Blanco. Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes. J. Cell Biochem. 111:834–845, 2010.
Aung, A., G. Gupta, G. Majid, and S. Varghese. Osteoarthritic chondrocyte-secreted morphogens induce chondrogenic differentiation of human mesenchymal stem cells. Arthritis Rheum. 63:148–158, 2011.
Baksh, D., L. Song, and R. S. Tuan. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J. Cell Mol. Med. 8:301–316, 2004.
Baksh, D., R. Yao, and R. S. Tuan. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells 25:1384–1392, 2007.
Barbero, A., S. Grogan, D. Schafer, M. Heberer, P. Mainil-Varlet, and I. Martin. Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacity. Osteoarthr. Cartil. 12:476–484, 2004.
Bark, S., T. Piontek, P. Behrens, S. Mkalaluh, D. Varoga, and J. Gille. Enhanced microfracture techniques in cartilage knee surgery: fact or fiction? World J. Orthop. 5:444–449, 2014.
Bartlett, W., J. A. Skinner, C. R. Gooding, R. W. Carrington, A. M. Flanagan, T. W. Briggs, and G. Bentley. Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. J. Bone Joint Surg. Br. 87:640–645, 2005.
Bathe, M., G. C. Rutledge, A. J. Grodzinsky, and B. Tidor. A coarse-grained molecular model for glycosaminoglycans: application to chondroitin, chondroitin sulfate, and hyaluronic acid. Biophys. J. 88:3870–3887, 2005.
Batty, L., S. Dance, S. Bajaj, and B. J. Cole. Autologous chondrocyte implantation: an overview of technique and outcomes. ANZ J. Surg. 81:18–25, 2011.
Baxter, M. A., R. F. Wynn, S. N. Jowitt, J. E. Wraith, L. J. Fairbairn, and I. Bellantuono. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells 22:675–682, 2004.
Beiser, I. H., and I. O. Kanat. Subchondral bone drilling: a treatment for cartilage defects. J. Foot Surg. 29:595–601, 1990.
Bernstein, P., M. Dong, S. Graupher, D. Corbeil, M. Gelinsky, K. P. Gunther, and S. Fickert. Sox9 expression of alginate-encapsulated chondrocytes is stimulated by low cell density. J. Biomed. Mater. Res. A 91:910–918, 2009.
Bian, L., D. Y. Zhai, R. L. Mauck, and J. A. Burdick. Coculture of human mesenchymal stem cells and articular chondrocytes reduces hypertrophy and enhances functional properties of engineered cartilage. Tissue Eng. Part A 17:1137–1145, 2011.
Bieback, K., S. Kern, A. Kocaomer, K. Ferlik, and P. Bugert. Comparing mesenchymal stromal cells from different human tissues: bone marrow, adipose tissue and umbilical cord blood. Biomed. Mater. Eng. 18:S71–S76, 2008.
Bohme, K., K. H. Winterhalter, and P. Bruckner. Terminal differentiation of chondrocytes in culture is a spontaneous process and is arrested by transforming growth factor-beta 2 and basic fibroblast growth factor in synergy. Exp. Cell Res. 216:191–198, 1995.
Brittberg, M., A. Lindahl, A. Nilsson, C. Ohlsson, O. Isaksson, and L. Peterson. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N. Engl. J. Med. 331:889–895, 1994.
Buckwalter, J. A. Articular cartilage injuries. Clin. Orthop. Relat. Res. 402:21–37, 2002.
Buravkova, L. B., E. R. Andreeva, V. Gogvadze, and B. Zhivotovsky. Mesenchymal stem cells and hypoxia: where are we? Mitochondrion 19 Pt A:105–112, 2014.
Candrian, C., D. Vonwil, A. Barbero, E. Bonacina, S. Miot, J. Farhadi, D. Wirz, S. Dickinson, A. Hollander, M. Jakob, Z. Li, M. Alini, M. Heberer, and I. Martin. Engineered cartilage generated by nasal chondrocytes is responsive to physical forces resembling joint loading. Arthritis Rheum. 58:197–208, 2008.
Chang, Q., W. D. Cui, and W. M. Fan. Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components. Braz. J. Med. Biol. Res. 44:303–310, 2011.
Chen, W. H., M. T. Lai, A. T. Wu, C. C. Wu, J. G. Gelovani, C. T. Lin, S. C. Hung, W. T. Chiu, and W. P. Deng. In vitro stage-specific chondrogenesis of mesenchymal stem cells committed to chondrocytes. Arthritis Rheum. 60:450–459, 2009.
Chen, F. H., K. T. Rousche, and R. S. Tuan. Technology insight: adult stem cells in cartilage regeneration and tissue engineering. Nat. Clin. Pract. Rheumatol. 2:373–382, 2006.
Cherubino, P., F. A. Grassi, P. Bulgheroni, and M. Ronga. Autologous chondrocyte implantation using a bilayer collagen membrane: a preliminary report. J. Orthop. Surg. 11:10–15, 2003.
Cheung, W. H., K. M. Lee, K. P. Fung, P. Y. Lui, and K. S. Leung. TGF-beta1 is the factor secreted by proliferative chondrocytes to inhibit neo-angiogenesis. J. Cell Biochem. Suppl. 36:79–88, 2001.
Chu, C. R., M. Szczodry, and S. Bruno. Animal models for cartilage regeneration and repair. Tissue Eng. Part B Rev. 16:105–115, 2010.
Cook, J. L., C. T. Hung, K. Kuroki, A. M. Stoker, C. R. Cook, F. M. Pfeiffer, S. L. Sherman, and J. P. Stannard. Animal models of cartilage repair. Bone Joint Res. 3:89–94, 2014.
Cooke, M. E., A. A. Allon, T. Cheng, A. C. Kuo, H. T. Kim, T. P. Vail, R. S. Marcucio, R. A. Schneider, J. C. Lotz, and T. Alliston. Structured three-dimensional co-culture of mesenchymal stem cells with chondrocytes promotes chondrogenic differentiation without hypertrophy. Osteoarthr. Cartil. 19:1210–1218, 2011.
da Silva Meirelles, L., P. C. Chagastelles, and N. B. Nardi. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J. Cell Sci. 119:2204–2213, 2006.
Dahlin, R. L., L. A. Kinard, J. Lam, C. J. Needham, S. Lu, F. K. Kasper, and A. G. Mikos. Articular chondrocytes and mesenchymal stem cells seeded on biodegradable scaffolds for the repair of cartilage in a rat osteochondral defect model. Biomaterials 35:7460–7469, 2014.
Dahlin, R. L., M. Ni, V. V. Meretoja, F. K. Kasper, and A. G. Mikos. TGF-beta3-induced chondrogenesis in co-cultures of chondrocytes and mesenchymal stem cells on biodegradable scaffolds. Biomaterials 35:123–132, 2014.
De Bari, C., F. Dell’Accio, and F. P. Luyten. Failure of in vitro-differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo. Arthritis Rheum. 50:142–150, 2004.
De Bari, C., F. Dell’Accio, P. Tylzanowski, and F. P. Luyten. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 44:1928–1942, 2001.
Diao, H. J., C. W. Yeung, C. H. Yan, G. C. Chan, and B. P. Chan. Bidirectional and mutually beneficial interactions between human mesenchymal stem cells and osteoarthritic chondrocytes in micromass co-cultures. Regen. Med. 8:257–269, 2013.
Dickhut, A., K. Pelttari, P. Janicki, W. Wagner, V. Eckstein, M. Egermann, and W. Richter. Calcification or dedifferentiation: requirement to lock mesenchymal stem cells in a desired differentiation stage. J. Cell Physiol. 219:219–226, 2009.
Djouad, F., B. Delorme, M. Maurice, C. Bony, F. Apparailly, P. Louis-Plence, F. Canovas, P. Charbord, D. Noel, and C. Jorgensen. Microenvironmental changes during differentiation of mesenchymal stem cells towards chondrocytes. Arthritis Res. Ther. 9:R33, 2007.
Dominici, M., K. Le Blanc, I. Mueller, I. Slaper-Cortenbach, F. Marini, D. Krause, R. Deans, A. Keating, D. Prockop, and E. Horwitz. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317, 2006.
Erices, A., P. Conget, and J. J. Minguell. Mesenchymal progenitor cells in human umbilical cord blood. Br. J. Haematol. 109:235–242, 2000.
Fehrer, C., and G. Lepperdinger. Mesenchymal stem cell aging. Exp. Gerontol. 40:926–930, 2005.
Fischer, J., A. Dickhut, M. Rickert, and W. Richter. Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis. Arthritis Rheum. 62:2696–2706, 2010.
Foldager, C. B. Advances in autologous chondrocyte implantation and related techniques for cartilage repair. Dan. Med. J. 60:B4600, 2013.
Foldager, C. B., C. Bunger, A. B. Nielsen, M. Ulrich-Vinther, S. Munir, H. Everland, and M. Lind. Dermatan sulphate in methoxy polyethylene glycol-polylactide-co-glycolic acid scaffolds upregulates fibronectin gene expression but has no effect on in vivo osteochondral repair. Int. Orthop. 36:1507–1513, 2012.
Foldager, C. B., S. Munir, M. Ulrik-Vinther, K. Soballe, C. Bunger, and M. Lind. Validation of suitable house keeping genes for hypoxia-cultured human chondrocytes. BMC Mol. Biol. 10:1471–2199, 2009.
Foldager, C. B., A. B. Nielsen, S. Munir, M. Ulrich-Vinther, K. Soballe, C. Bunger, and M. Lind. Combined 3D and hypoxic culture improves cartilage-specific gene expression in human chondrocytes. Acta Orthop. 82:234–240, 2011.
Francioli, S. E., C. Candrian, K. Martin, M. Heberer, I. Martin, and A. Barbero. Effect of three-dimensional expansion and cell seeding density on the cartilage-forming capacity of human articular chondrocytes in type II collagen sponges. J. Biomed. Mater. Res. A 95:924–931, 2010.
Fraser, J. K., I. Wulur, Z. Alfonso, and M. H. Hedrick. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol. 24:150–154, 2006.
Fu, W. L., C. Y. Zhou, and J. K. Yu. 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. Am. J. Sports Med. 10:10, 2013.
Giovannini, S., J. Diaz-Romero, T. Aigner, P. Heini, P. Mainil-Varlet, and D. Nesic. Micromass co-culture of human articular chondrocytes and human bone marrow mesenchymal stem cells to investigate stable neocartilage tissue formation in vitro. Eur. Cells Mater. 20:245–259, 2010.
Glowacki, J., and S. Mizuno. Collagen scaffolds for tissue engineering. Biopolymers 89:338–344, 2008.
Goldring, M. B., and K. B. Marcu. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res. Ther. 11:19, 2009.
Goldring, M. B., M. Otero, D. A. Plumb, C. Dragomir, M. Favero, K. El Hachem, K. Hashimoto, H. I. Roach, E. Olivotto, R. M. Borzi, and K. B. Marcu. Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur. Cell Mater. 21:202–220, 2011.
Gooding, C. R., W. Bartlett, G. Bentley, J. A. Skinner, R. Carrington, and A. Flanagan. A prospective, randomised study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: periosteum covered versus type I/III collagen covered. Knee 13:203–210, 2006.
Grad, S., D. Eglin, M. Alini, and M. J. Stoddart. Physical stimulation of chondrogenic cells in vitro: a review. Clin. Orthop. Relat. Res. 469:2764–2772, 2011.
Han, B., J. Li, Z. Li, L. Guo, S. Wang, P. Liu, and Y. Wu. Trichostatin A stabilizes the expression of pluripotent genes in human mesenchymal stem cells during ex vivo expansion. PLoS One 8:e81781, 2013.
Hansen, O. M., C. B. Foldager, B. B. Christensen, H. Everland, and M. Lind. Increased chondrocyte seeding density has no positive effect on cartilage repair in an MPEG-PLGA scaffold. Knee Surg. Sports Traumatol. Arthrosc. 21:485–493, 2013.
Hao, H., G. Chen, J. Liu, D. Ti, Y. Zhao, S. Xu, X. Fu, and W. Han. Culturing on Wharton’s jelly extract delays mesenchymal stem cell senescence through p53 and p16INK4a/pRb pathways. Plos One 8:13, 2013.
Heath, C. A., and S. R. Magari. Mini-review: mechanical factors affecting cartilage regeneration in vitro. Biotechnol. Bioeng. 50:430–437, 1996.
Hildner, F., S. Concaro, A. Peterbauer, S. Wolbank, M. Danzer, A. Lindahl, P. Gatenholm, H. Redl, and M. van Griensven. Human adipose-derived stem cells contribute to chondrogenesis in coculture with human articular chondrocytes. Tissue Eng. Part A 15:3961–3969, 2009.
Hilkens, P., P. Gervois, Y. Fanton, J. Vanormelingen, W. Martens, T. Struys, C. Politis, I. Lambrichts, and A. Bronckaers. Effect of isolation methodology on stem cell properties and multilineage differentiation potential of human dental pulp stem cells. Cell Tissue Res. 353:65–78, 2013.
Hubka, K. M., R. L. Dahlin, V. V. Meretoja, F. K. Kasper, and A. G. Mikos. Enhancing chondrogenic phenotype for cartilage tissue engineering: monoculture and coculture of articular chondrocytes and mesenchymal stem cells. Tissue Eng. Part B Rev. 20:641–654, 2014.
Hunziker, E. B. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr. Cartil. 10:432–463, 2002.
Hwang, N. S., and J. Elisseeff. Application of stem cells for articular cartilage regeneration. J. Knee Surg. 22:60–71, 2009.
Hwang, N. S., S. G. Im, P. B. Wu, D. A. Bichara, X. Zhao, M. A. Randolph, R. Langer, and D. G. Anderson. Chondrogenic priming adipose-mesenchymal stem cells for cartilage tissue regeneration. Pharm. Res. 28:1395–1405, 2011.
Hwang, N. S., S. Varghese, C. Puleo, Z. Zhang, and J. Elisseeff. Morphogenetic signals from chondrocytes promote chondrogenic and osteogenic differentiation of mesenchymal stem cells. J. Cell Physiol. 212:281–284, 2007.
Ikenoue, T., M. C. Trindade, M. S. Lee, E. Y. Lin, D. J. Schurman, S. B. Goodman, and R. L. Smith. Mechanoregulation of human articular chondrocyte aggrecan and type II collagen expression by intermittent hydrostatic pressure in vitro. J. Orthop. Res. 21:110–116, 2003.
Im, G. I., Y. W. Shin, and K. B. Lee. Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthr. Cartil. 13:845–853, 2005.
In ‘t Anker, P. S., S. A. Scherjon, C. Kleijburg-van der Keur, G. M. de Groot-Swings, F. H. Claas, W. E. Fibbe, and H. H. Kanhai. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 22:1338–1345, 2004.
Inada, M., Y. Wang, M. H. Byrne, M. U. Rahman, C. Miyaura, C. Lopez-Otin, and S. M. Krane. Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification. Proc. Natl. Acad. Sci. USA 101:17192–17197, 2004.
Iwata, H., S. Ono, K. Sato, T. Sato, and M. Kawamura. Bone morphogenetic protein-induced muscle- and synovium-derived cartilage differentiation in vitro. Clin. Orthop. Relat. Res. 296:295–300, 1993.
Izadpanah, R., C. Trygg, B. Patel, C. Kriedt, J. Dufour, J. M. Gimble, and B. A. Bunnell. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J. Cell Biochem. 99:1285–1297, 2006.
Jakob, M., O. Demarteau, D. Schafer, B. Hintermann, W. Dick, M. Heberer, and I. Martin. Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro. J. Cell Biochem. 81:368–377, 2001.
Jakob, M., O. Demarteau, D. Schafer, M. Stumm, M. Heberer, and I. Martin. Enzymatic digestion of adult human articular cartilage yields a small fraction of the total available cells. Connect. Tissue Res. 44:173–180, 2003.
Johnson, T. S., J. W. Xu, V. V. Zaporojan, J. M. Mesa, C. Weinand, M. A. Randolph, L. J. Bonassar, J. M. Winograd, and M. J. Yaremchuk. Integrative repair of cartilage with articular and nonarticular chondrocytes. Tissue Eng. 10:1308–1315, 2004.
Johnson, K., S. T. Zhu, M. S. Tremblay, J. N. Payette, J. N. Wang, L. C. Bouchez, S. Meeusen, A. Althage, C. Y. Cho, X. Wu, and P. G. Schultz. A stem cell-based approach to cartilage repair. Science 336:717–721, 2012.
Johnstone, B., T. M. Hering, A. I. Caplan, V. M. Goldberg, and J. U. Yoo. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp. Cell Res. 238:265–272, 1998.
Jonitz, A., K. Lochner, T. Tischer, D. Hansmann, and R. Bader. TGF-beta1 and IGF-1 influence the re-differentiation capacity of human chondrocytes in 3D pellet cultures in relation to different oxygen concentrations. Int. J. Mol. Med. 30:666–672, 2012.
Kafienah, W., M. Jakob, O. Demarteau, A. Frazer, M. D. Barker, I. Martin, and A. P. Hollander. Three-dimensional tissue engineering of hyaline cartilage: comparison of adult nasal and articular chondrocytes. Tissue Eng. 8:817–826, 2002.
Kane, P., R. Frederick, B. Tucker, C. C. Dodson, J. A. Anderson, M. G. Ciccotti, and K. B. Freedman. Surgical restoration/repair of articular cartilage injuries in athletes. Phys. Sportsmed. 41:75–86, 2013.
Keller, B., T. Yang, Y. Chen, E. Munivez, T. Bertin, B. Zabel, and B. Lee. Interaction of TGFbeta and BMP signaling pathways during chondrogenesis. PLoS One 6:0016421, 2011.
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 24:1294–1301, 2006.
Kim, Y. J., H. J. Kim, and G. I. Im. PTHrP promotes chondrogenesis and suppresses hypertrophy from both bone marrow-derived and adipose tissue-derived MSCs. Biochem. Biophys. Res. Commun. 373:104–108, 2008.
Kim, J. S., Z. Y. Ryoo, and J. S. Chun. Cytokine-like 1 (Cytl1) regulates the chondrogenesis of mesenchymal cells. J. Biol. Chem. 282:29359–29367, 2007.
Kino-Oka, M., S. Yashiki, Y. Ota, Y. Mushiaki, K. Sugawara, T. Yamamoto, T. Takezawa, and M. Taya. Subculture of chondrocytes on a collagen type I-coated substrate with suppressed cellular dedifferentiation. Tissue Eng. 11:597–608, 2005.
Knauper, V., S. Cowell, B. Smith, C. Lopez-Otin, M. O’Shea, H. Morris, L. Zardi, and G. Murphy. The role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction. J. Biol. Chem. 272:7608–7616, 1997.
Knutsen, G., J. O. Drogset, L. Engebretsen, T. Grontvedt, V. Isaksen, T. C. Ludvigsen, S. Roberts, E. Solheim, T. Strand, and O. Johansen. A Randomized trial comparing autologous chondrocyte implantation with microfracture. J. Bone Joint Surg. Am. 89A:2105–2112, 2007.
Komarek, J., P. Valis, M. Repko, R. Chaloupka, and M. Krbec. Treatment of deep cartilage defects of the knee with autologous chondrocyte transplantation: long-term results. Acta Chir. Orthop. Traumatol. Cech. 77:291–295, 2010.
Kon, E., A. Roffi, G. Filardo, G. Tesei, and M. Marcacci. Scaffold-based cartilage treatments: with or without cells? A systematic review of preclinical and clinical evidence. Arthroscopy 31:767–775, 2015.
Kurtz, S., K. Ong, E. Lau, F. Mowat, and M. Halpern. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J. Bone Joint Surg. Am. 89:780–785, 2007.
Lee, J. S., and G. I. Im. Influence of chondrocytes on the chondrogenic differentiation of adipose stem cells. Tissue Eng. Part A 16:3569–3577, 2010.
Lee, R. H., B. Kim, I. Choi, H. Kim, H. S. Choi, K. Suh, Y. C. Bae, and J. S. Jung. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell. Physiol. Biochem. 14:311–324, 2004.
Leyh, M., A. Seitz, L. Durselen, J. Schaumburger, A. Ignatius, J. Grifka, and S. Grassel. Subchondral bone influences chondrogenic differentiation and collagen production of human bone marrow-derived mesenchymal stem cells and articular chondrocytes. Arthritis Res. Ther. 16:453, 2014.
Leyh, M., A. Seitz, L. Dürselen, H. R. Springorum, P. Angele, A. Ignatius, J. Grifka, and S. Grässel. Osteoarthritic cartilage explants affect extracellular matrix production and composition in cocultured bone marrow-derived mesenchymal stem cells and articular chondrocytes. Stem Cell Res. Ther. 5:77, 2014.
Li, Z., C. Liu, Z. Xie, P. Song, R. C. Zhao, L. Guo, Z. Liu, and Y. Wu. Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation. PLoS One 6:9, 2011.
Lopa, S., A. Colombini, V. Sansone, F. W. Preis, and M. Moretti. Influence on chondrogenesis of human osteoarthritic chondrocytes in co-culture with donor-matched mesenchymal stem cells from infrapatellar fat pad and subcutaneous adipose tissue. Int. J. Immunopathol. Pharmacol. 26:23–31, 2013.
Lutolf, M. P., and J. A. Hubbell. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat. Biotechnol. 23:47–55, 2005.
Ma, B., J. C. Leijten, L. Wu, M. Kip, C. A. van Blitterswijk, J. N. Post, and M. Karperien. Gene expression profiling of dedifferentiated human articular chondrocytes in monolayer culture. Osteoarthr. Cartil. 21:599–603, 2013.
Mahmoudifar, N., and P. M. Doran. Effect of seeding and bioreactor culture conditions on the development of human tissue-engineered cartilage. Tissue Eng. 12:1675–1685, 2006.
Makris, E. A., A. H. Gomoll, K. N. Malizos, J. C. Hu, and K. A. Athanasiou. Repair and tissue engineering techniques for articular cartilage. Nat. Rev. Rheumatol. 11:21–34, 2015.
Manferdini, C., M. Maumus, E. Gabusi, A. Piacentini, G. Filardo, J. A. Peyrafitte, C. Jorgensen, P. Bourin, S. Fleury-Cappellesso, A. Facchini, D. Noel, and G. Lisignoli. Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2. Arthritis Rheum. 65:1271–1281, 2013.
Marcacci, M., S. Zaffagnini, E. Kon, A. Visani, F. Iacono, and I. Loreti. Arthroscopic autologous chondrocyte transplantation: technical note. Knee Surg. Sports Traumatol. Arthrosc. 10:154–159, 2002.
Maumus, M., C. Manferdini, K. Toupet, J. A. Peyrafitte, R. Ferreira, A. Facchini, E. Gabusi, P. Bourin, C. Jorgensen, G. Lisignoli, and D. Noel. Adipose mesenchymal stem cells protect chondrocytes from degeneration associated with osteoarthritis. Stem Cell Res. 11:834–844, 2013.
Mayan, M. D., P. Carpintero-Fernandez, R. Gago-Fuentes, O. Martinez-de-Ilarduya, H. Z. Wang, V. Valiunas, P. Brink, and F. J. Blanco. Human articular chondrocytes express multiple gap junction proteins: differential expression of connexins in normal and osteoarthritic cartilage. Am. J. Pathol. 12:018, 2013.
Mehlhorn, A. T., P. Niemeyer, S. Kaiser, G. Finkenzeller, G. B. Stark, N. P. Sudkamp, and H. Schmal. Differential expression pattern of extracellular matrix molecules during chondrogenesis of mesenchymal stem cells from bone marrow and adipose tissue. Tissue Eng. 12:2853–2862, 2006.
Mesallati, T., E. J. Sheehy, T. Vinardell, C. T. Buckley, and D. J. Kelly. Tissue engineering scaled-up, anatomically shaped osteochondral constructs for joint resurfacing. Eur. Cell Mater. 30:163–185, 2015; (discussion 185–166).
Micheli, L. J., J. E. Browne, C. Erggelet, F. Fu, B. Mandelbaum, J. B. Moseley, and D. Zurakowski. Autologous chondrocyte implantation of the knee: multicenter experience and minimum 3-year follow-up. Clin. J. Sport Med. 11:223–228, 2001.
Miller, M. J., S. Ahmed, P. Bobrowski, and T. M. Haqqi. The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta. BMC Complement Altern. Med. 6:13, 2006.
Minas, T. Autologous chondrocyte implantation for focal chondral defects of the knee. Clin. Orthop. Relat. Res. 391:S349–S361, 2001.
Mo, X.-T., S.-C. Guo, H.-Q. Xie, L. Deng, W. Zhi, Z. Xiang, X.-Q. Li, and Z.-M. Yang. Variations in the ratios of co-cultured mesenchymal stem cells and chondrocytes regulate the expression of cartilaginous and osseous phenotype in alginate constructs. Bone 45:42–51, 2009.
Moriguchi, Y., K. Tateishi, W. Ando, K. Shimomura, Y. Yonetani, Y. Tanaka, K. Kita, D. A. Hart, A. Gobbi, K. Shino, H. Yoshikawa, and N. Nakamura. Repair of meniscal lesions using a scaffold-free tissue-engineered construct derived from allogenic synovial MSCs in a miniature swine model. Biomaterials 34:2185–2193, 2013.
Munir, S., C. B. Foldager, M. Lind, V. Zachar, K. Soballe, and T. G. Koch. Hypoxia enhances chondrogenic differentiation of human adipose tissue-derived stromal cells in scaffold-free and scaffold systems. Cell Tissue Res. 1:1, 2013.
Murphy, L., T. A. Schwartz, C. G. Helmick, J. B. Renner, G. Tudor, G. Koch, A. Dragomir, W. D. Kalsbeek, G. Luta, and J. M. Jordan. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum. 59:1207–1213, 2008.
Musgrave, D. S., R. Pruchnic, V. Wright, P. Bosch, S. C. Ghivizzani, P. D. Robbins, and J. Huard. The effect of bone morphogenetic protein-2 expression on the early fate of skeletal muscle-derived cells. Bone 28:499–506, 2001.
Mwale, F., G. Yao, J. A. Ouellet, A. Petit, and J. Antoniou. Effect of parathyroid hormone on type X and type II collagen expression in mesenchymal stem cells from osteoarthritic patients. Tissue Eng. Part A 16:3449–3455, 2010.
Nejadnik, H., J. H. Hui, E. P. Feng Choong, B. C. Tal, and E. H. Lee. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am. J. Sports Med. 38:1110–1116, 2010.
Nevo, Z., A. Beit-Or, and Y. Eilam. Slowing down aging of cultured embryonal chick chondrocytes by maintenance under lowered oxygen tension. Mech. Ageing Dev. 45:157–165, 1988.
Ng, L., A. J. Grodzinsky, P. Patwari, J. Sandy, A. Plaas, and C. Ortiz. Individual cartilage aggrecan macromolecules and their constituent glycosaminoglycans visualized via atomic force microscopy. J. Struct. Biol. 143:242–257, 2003.
Noer, A., L. C. Lindeman, and P. Collas. Histone H3 modifications associated with differentiation and long-term culture of mesenchymal adipose stem cells. Stem Cells Dev. 18:725–736, 2009.
O’Driscoll, S. W. Preclinical cartilage repair: current status and future perspectives. Clin. Orthop. Relat. Res. 391:S397–S401, 2001.
Pelttari, K., B. Pippenger, M. Mumme, S. Feliciano, C. Scotti, P. Mainil-Varlet, A. Procino, B. von Rechenberg, T. Schwamborn, M. Jakob, C. Cillo, A. Barbero, and I. Martin. Adult human neural crest-derived cells for articular cartilage repair. Sci. Transl. Med. 6:251ra119, 2014.
Pelttari, K., A. Winter, E. Steck, K. Goetzke, T. Hennig, B. G. Ochs, T. Aigner, and W. Richter. 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. 54:3254–3266, 2006.
Peterson, L., M. Brittberg, I. Kiviranta, E. L. Akerlund, and A. Lindahl. Autologous chondrocyte transplantation. Biomechanics and long-term durability. Am. J. Sports Med. 30:2–12, 2002.
Peterson, L., T. Minas, M. Brittberg, and A. Lindahl. Treatment of osteochondritis dissecans of the knee with autologous chondrocyte transplantation: results at two to ten years. J. Bone Joint Surg. Am. 2:17–24, 2003.
Pfeiffer, E., S. M. Vickers, E. Frank, A. J. Grodzinsky, and M. Spector. The effects of glycosaminoglycan content on the compressive modulus of cartilage engineered in type II collagen scaffolds. Osteoarthr. Cartil. 16:1237–1244, 2008.
Pittenger, M. F., A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas, J. D. Mosca, M. A. Moorman, D. W. Simonetti, S. Craig, and D. R. Marshak. Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147, 1999.
Poole, A. R., T. Kojima, T. Yasuda, F. Mwale, M. Kobayashi, and S. Laverty. Composition and structure of articular cartilage: a template for tissue repair. Clin. Orthop. Relat. Res. 391:S26–S33, 2001.
Redman, S. N., S. F. Oldfield, and C. W. Archer. Current strategies for articular cartilage repair. Eur. Cell Mater. 9:23–32, 2005.
Richardson, S. M., R. V. Walker, S. Parker, N. P. Rhodes, J. A. Hunt, A. J. Freemont, and J. A. Hoyland. Intervertebral disc cell-mediated mesenchymal stem cell differentiation. Stem Cells 24:707–716, 2006.
Rider, D. A., C. Dombrowski, A. A. Sawyer, G. H. Ng, D. Leong, D. W. Hutmacher, V. Nurcombe, and S. M. Cool. Autocrine fibroblast growth factor 2 increases the multipotentiality of human adipose-derived mesenchymal stem cells. Stem Cells 26:1598–1608, 2008.
Ronziere, M. C., E. Perrier, F. Mallein-Gerin, and A. M. Freyria. Chondrogenic potential of bone marrow- and adipose tissue-derived adult human mesenchymal stem cells. Biomed. Mater. Eng. 20:145–158, 2010.
Rotter, N., L. J. Bonassar, G. Tobias, M. Lebl, A. K. Roy, and C. A. Vacanti. Age dependence of biochemical and biomechanical properties of tissue-engineered human septal cartilage. Biomaterials 23:3087–3094, 2002.
Russlies, M., P. Behrens, E. M. Ehlers, C. Brohl, C. Vindigni, M. Spector, and B. Kurz. Periosteum stimulates subchondral bone densification in autologous chondrocyte transplantation in a sheep model. Cell Tissue Res. 319:133–142, 2005.
Schroer, W. C., K. R. Berend, A. V. Lombardi, C. L. Barnes, M. P. Bolognesi, M. E. Berend, M. A. Ritter, and R. M. Nunley. Why are total knees failing today? Etiology of total knee revision in 2010 and 2011. J. Arthroplast. 28:116–119, 2013.
Scotti, C., A. Osmokrovic, F. Wolf, S. Miot, G. M. Peretti, A. Barbero, and I. Martin. Response of human engineered cartilage based on articular or nasal chondrocytes to interleukin-1beta and low oxygen. Tissue Eng. Part A 18:362–372, 2012.
Seror, J., Y. Merkher, N. Kampf, L. Collinson, A. J. Day, A. Maroudas, and J. Klein. Articular cartilage proteoglycans as boundary lubricants: structure and frictional interaction of surface-attached hyaluronan and hyaluronan–aggrecan complexes. Biomacromolecules 12:3432–3443, 2011.
Shakibaei, M., P. De Souza, and H. J. Merker. Integrin expression and collagen type II implicated in maintenance of chondrocyte shape in monolayer culture: an immunomorphological study. Cell Biol. Int. 21:115–125, 1997.
Shapiro, F., S. Koide, and M. J. Glimcher. Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J. Bone Joint Surg. Am. 75:532–553, 1993.
Shen, Y., Y. Fu, J. Wang, G. Li, X. Zhang, Y. Xu, and Y. Lin. Biomaterial and mesenchymal stem cell for articular cartilage reconstruction. Curr. Stem Cell Res. Ther. 9:254–267, 2014.
Shintani, N., and E. B. Hunziker. Differential effects of dexamethasone on the chondrogenesis of mesenchymal stromal cells: influence of microenvironment, tissue origin and growth factor. Eur. Cell Mater. 22:302–319, 2011.
Shipley, R. J., and S. L. Waters. Fluid and mass transport modelling to drive the design of cell-packed hollow fibre bioreactors for tissue engineering applications. Math. Med. Biol. 29:329–359, 2012.
Singh, S., C. C. Lee, and B. K. Tay. Results of arthroscopic abrasion arthroplasty in osteoarthritis of the knee joint. Singap. Med. J. 32:34–37, 1991.
Sledge, S. L. Microfracture techniques in the treatment of osteochondral injuries. Clin. Sports Med. 20:365–377, 2001.
Slynarski, K., W. Widuchowski, M. Snow, W. Weiss, J. Kruczynski, J. Hendriks, J. Guidoux, and P. Verdonk. Primary chondrocytes and bone marrow cells on a 3D co-polymer scaffold: 2-year results of a prospective, multicenter, single-arm clinical trial in patients with cartilage defects of the knee. Revue de Chirurgie Orthopédique et Traumatologique 101:e17–e18, 2015.
Solorio, L. D., E. L. Vieregge, C. D. Dhami, and E. Alsberg. High-density cell systems incorporating polymer microspheres as microenvironmental regulators in engineered cartilage tissues. Tissue Eng. Part B Rev. 19:209–220, 2013.
Stickens, D., D. J. Behonick, N. Ortega, B. Heyer, B. Hartenstein, Y. Yu, A. J. Fosang, M. Schorpp-Kistner, P. Angel, and Z. Werb. Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Development 131:5883–5895, 2004.
Stockwell, R. A. The cell density of human articular and costal cartilage. J. Anat. 101:753–763, 1967.
Tan, J., H. Huang, W. Huang, L. Li, J. Guo, B. Huang, and J. Lu. The genomic landscapes of histone H3-Lys9 modifications of gene promoter regions and expression profiles in human bone marrow mesenchymal stem cells. J. Genet. Genom. 35:585–593, 2008.
Taylor, D. W., N. Ahmed, L. Gan, A. E. Gross, and R. A. Kandel. Proteoglycan and collagen accumulation by passaged chondrocytes can be enhanced through side-by-side culture with primary chondrocytes. Tissue Eng. Part A 16:643–651, 2010.
Thorpe, S. D., T. Nagel, S. F. Carroll, and D. J. Kelly. Modulating gradients in regulatory signals within mesenchymal stem cell seeded hydrogels: a novel strategy to engineer zonal articular cartilage. PLoS One 8:e60764, 2013.
Toyoda, T., B. B. Seedhom, J. Q. Yao, J. Kirkham, S. Brookes, and W. A. Bonass. Hydrostatic pressure modulates proteoglycan metabolism in chondrocytes seeded in agarose. Arthritis Rheum. 48:2865–2872, 2003.
Tsuchiya, K., G. Chen, T. Ushida, T. Matsuno, and T. Tateishi. The effect of coculture of chondrocytes with mesenchymal stem cells on their cartilaginous phenotype in vitro. Mater. Sci. Eng. C 24:391–396, 2004.
Tuli, R., W. J. Li, and R. S. Tuan. Current state of cartilage tissue engineering. Arthritis Research & Therapy 5:235–238, 2003.
Ulrich-Vinther, M., M. D. Maloney, E. M. Schwarz, R. Rosier, and R. J. O’Keefe. Articular cartilage biology. J. Am. Acad. Orthop. Surg. 11:421–430, 2003.
Vavken, P., F. Arrich, M. Pilz, and R. Dorotka. An in vitro model of biomaterial-augmented microfracture including chondrocyte-progenitor cell interaction. Arch. Orthop. Trauma Surg. 130:711–716, 2010.
Villiger, P. M., and M. Lotz. Differential expression of TGF beta isoforms by human articular chondrocytes in response to growth factors. J. Cell Physiol. 151:318–325, 1992.
Viste, A., M. Piperno, R. Desmarchelier, S. Grosclaude, B. Moyen, and M. H. Fessy. Autologous chondrocyte implantation for traumatic full-thickness cartilage defects of the knee in 14 patients: 6-year functional outcomes. Orthop. Traumatol. Surg. Res. 98:737–743, 2012.
von der Mark, K., V. Gauss, H. von der Mark, and P. Muller. Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture. Nature 267:531–532, 1977.
Vunjak-Novakovic, G., L. E. Freed, R. J. Biron, and R. Langer. Effects of mixing on the composition and morphology of tissue-engineered cartilage. AIChE J. 42:850–860, 1996.
Wakitani, S., K. Imoto, T. Yamamoto, M. Saito, N. Murata, and M. Yoneda. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthr. Cartil. 10:199–206, 2002.
Wakitani, S., T. Mitsuoka, N. Nakamura, Y. Toritsuka, Y. Nakamura, and S. Horibe. Autologous bone marrow stromal cell transplantation for repair of full-thickness articular cartilage defects in human patellae: two case reports. Cell Transpl. 13:595–600, 2004.
Wakitani, S., M. Nawata, K. Tensho, T. Okabe, H. Machida, and H. Ohgushi. Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J. Tissue Eng. Regen. Med. 1:74–79, 2007.
Wakitani, S., T. Okabe, S. Horibe, T. Mitsuoka, M. Saito, T. Koyama, M. Nawata, K. Tensho, H. Kato, K. Uematsu, R. Kuroda, M. Kurosaka, S. Yoshiya, K. Hattori, and H. Ohgushi. Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J. Tissue Eng. Regen. Med. 5:146–150, 2011.
Wang, T. Y., and J. H. Wu. A continuous perfusion bioreactor for long-term bone marrow culture. Ann. N. Y. Acad. Sci. 665:274–284, 1992.
Watt, F. M. Effect of seeding density on stability of the differentiated phenotype of pig articular chondrocytes in culture. J. Cell Sci. 89(Pt 3):373–378, 1988.
Weiss, S., T. Hennig, R. Bock, E. Steck, and W. Richter. Impact of growth factors and PTHrP on early and late chondrogenic differentiation of human mesenchymal stem cells. J. Cell Physiol. 223:84–93, 2010.
Wescoe, K. E., R. C. Schugar, C. R. Chu, and B. M. Deasy. The role of the biochemical and biophysical environment in chondrogenic stem cell differentiation assays and cartilage tissue engineering. Cell Biochem. Biophys. 52:85–102, 2008.
Winter, A., S. Breit, D. Parsch, K. Benz, E. Steck, H. Hauner, R. M. Weber, V. Ewerbeck, and W. Richter. Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow-derived and adipose tissue-derived stromal cells. Arthritis Rheum. 48:418–429, 2003.
Wu, L., H. J. Prins, M. N. Helder, C. A. van Blitterswijk, and M. Karperien. Trophic effects of mesenchymal stem cells in chondrocyte co-cultures are independent of culture conditions and cell sources. Tissue Eng. Part A 18:1542–1551, 2012.
Yang, Y. H., A. J. Lee, and G. A. Barabino. Coculture-driven mesenchymal stem cell-differentiated articular chondrocyte-like cells support neocartilage development. Stem Cells Transl. Med. 1:843–854, 2012.
Yonenaga, K., S. Nishizawa, Y. Fujihara, Y. Asawa, K. Sanshiro, S. Nagata, T. Takato, and K. Hoshi. The optimal conditions of chondrocyte isolation and its seeding in the preparation for cartilage tissue engineering. Tissue Eng. Part C Methods 16:1461–1469, 2010.
Zaslav, K., B. Cole, R. Brewster, T. DeBerardino, J. Farr, P. Fowler, and C. Nissen. A prospective study of autologous chondrocyte implantation in patients with failed prior treatment for articular cartilage defect of the knee: results of the Study of the Treatment of Articular Repair (STAR) clinical trial. Am. J. Sports Med. 37:42–55, 2009.
Zeifang, F., D. Oberle, C. Nierhoff, W. Richter, B. Moradi, and H. Schmitt. Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: a randomized clinical trial. Am. J. Sports Med. 38:924–933, 2010.
Zhang, Y., L. Cao, C. Kiani, B. L. Yang, W. Hu, and B. B. Yang. Promotion of chondrocyte proliferation by versican mediated by G1 domain and EGF-like motifs. J. Cell Biochem. 73:445–457, 1999.
Zhang, L. M., P. Q. Su, C. X. Xu, J. L. Yang, W. H. Yu, and D. S. Huang. Chondrogenic differentiation of human mesenchymal stem cells: a comparison between micromass and pellet culture systems. Biotechnol. Lett. 32:1339–1346, 2010.
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. 7:211–228, 2001.
Zuo, Q., W. Cui, F. Liu, Q. Wang, Z. Chen, and W. Fan. Co-cultivated mesenchymal stem cells support chondrocytic differentiation of articular chondrocytes. Int. Orthop. 37:747–752, 2013.
The authors gratefully acknowledge NSF support through CBET EAGER Award #1212573, Regeneron Pharmaceuticals, Inc., and USDA NIFA WN.P WNP00807 for salary support. The efforts of Professor Elizabeth Siler in editing this manuscript are appreciated.
Conflict of interest
The authors have no conflict of interest to disclose.
Associate Editor Michael S. Detamore oversaw the review of this article.
About this article
Cite this article
Nazempour, A., Van Wie, B.J. Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine. Ann Biomed Eng 44, 1325–1354 (2016). https://doi.org/10.1007/s10439-016-1575-9
- Articular cartilage
- Articular cartilage tissue engineering
- Autologous chondrocyte implantation
- Mesenchymal stem cells
- Autologous mesenchymal stem cell transplantation
- Co-culture of mesenchymal stem cells with articular chondrocytes