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Published in: Arthritis Research & Therapy 1/2009

01-02-2009 | Review

Tissue engineering in the rheumatic diseases

Authors: Jochen Ringe, Michael Sittinger

Published in: Arthritis Research & Therapy | Issue 1/2009

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Abstract

Diseases such as degenerative or rheumatoid arthritis are accompanied by joint destruction. Clinically applied tissue engineering technologies like autologous chondrocyte implantation, matrix-assisted chondrocyte implantation, or in situ recruitment of bone marrow mesenchymal stem cells target the treatment of traumatic defects or of early osteoarthritis. Inflammatory conditions in the joint hamper the application of tissue engineering during chronic joint diseases. Here, most likely, cartilage formation is impaired and engineered neocartilage will be degraded. Based on the observations that mesenchymal stem cells (a) develop into joint tissues and (b) in vitro and in vivo show immunosuppressive and anti-inflammatory qualities indicating a transplant-protecting activity, these cells are prominent candidates for future tissue engineering approaches for the treatment of rheumatic diseases. Tissue engineering also provides highly organized three-dimensional in vitro culture models of human cells and their extracellular matrix for arthritis research.
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Literature
1.
go back to reference Simon TM, Jackson DW: Articular cartilage: injury pathways and treatment options. Sports Med Arthrosc. 2006, 14: 146-154. 10.1097/00132585-200609000-00006.CrossRefPubMed Simon TM, Jackson DW: Articular cartilage: injury pathways and treatment options. Sports Med Arthrosc. 2006, 14: 146-154. 10.1097/00132585-200609000-00006.CrossRefPubMed
2.
go back to reference Steadman JR, Ramappa AJ, Maxwell RB, Briggs KK: An arthroscopic treatment regimen for osteoarthritis of the knee. Arthroscopy. 2007, 23: 948-955.CrossRefPubMed Steadman JR, Ramappa AJ, Maxwell RB, Briggs KK: An arthroscopic treatment regimen for osteoarthritis of the knee. Arthroscopy. 2007, 23: 948-955.CrossRefPubMed
3.
go back to reference Hollander AP, Dickinson SC, Sims TJ, Brun P, Cortivo R, Kon E, Marcacci M, Zanasi S, Borrione A, De Luca C, Pavesio A, Soranzo C, Abatangelo G: Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees. Tissue Eng. 2006, 12: 1787-1798. 10.1089/ten.2006.12.1787.CrossRefPubMed Hollander AP, Dickinson SC, Sims TJ, Brun P, Cortivo R, Kon E, Marcacci M, Zanasi S, Borrione A, De Luca C, Pavesio A, Soranzo C, Abatangelo G: Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees. Tissue Eng. 2006, 12: 1787-1798. 10.1089/ten.2006.12.1787.CrossRefPubMed
4.
go back to reference Ossendorf C, Kaps C, Kreuz PC, Burmester GR, Sittinger M, Erggelet C: Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee with autologous polymer-based three-dimensional chondrocyte grafts: 2-year clinical results. Arthritis Res Ther. 2007, 9: R41-10.1186/ar2180.PubMedCentralCrossRefPubMed Ossendorf C, Kaps C, Kreuz PC, Burmester GR, Sittinger M, Erggelet C: Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee with autologous polymer-based three-dimensional chondrocyte grafts: 2-year clinical results. Arthritis Res Ther. 2007, 9: R41-10.1186/ar2180.PubMedCentralCrossRefPubMed
5.
go back to reference Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 1999, 284: 143-147. 10.1126/science.284.5411.143.CrossRefPubMed Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 1999, 284: 143-147. 10.1126/science.284.5411.143.CrossRefPubMed
6.
go back to reference Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU: In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 1998, 238: 265-272. 10.1006/excr.1997.3858.CrossRefPubMed Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU: In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 1998, 238: 265-272. 10.1006/excr.1997.3858.CrossRefPubMed
7.
go back to reference Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP: Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem. 1997, 64: 295-312. 10.1002/(SICI)1097-4644(199702)64:2<295::AID-JCB12>3.0.CO;2-I.CrossRefPubMed Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP: Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem. 1997, 64: 295-312. 10.1002/(SICI)1097-4644(199702)64:2<295::AID-JCB12>3.0.CO;2-I.CrossRefPubMed
8.
go back to reference Caplan AI, Dennis JE: Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006, 98: 1076-1084. 10.1002/jcb.20886.CrossRefPubMed Caplan AI, Dennis JE: Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006, 98: 1076-1084. 10.1002/jcb.20886.CrossRefPubMed
9.
go back to reference Jorgensen C, Djouad F, Bouffi C, Mrugala D, Noël D: Multipotent mesenchymal stromal cells in articular diseases. Best Pract Res Clin Rheumatol. 2008, 22: 269-284. 10.1016/j.berh.2008.01.005.CrossRefPubMed Jorgensen C, Djouad F, Bouffi C, Mrugala D, Noël D: Multipotent mesenchymal stromal cells in articular diseases. Best Pract Res Clin Rheumatol. 2008, 22: 269-284. 10.1016/j.berh.2008.01.005.CrossRefPubMed
10.
go back to reference Fedewa MM, Oegema TR, Schwartz MH, MacLeod A, Lewis JL: Chondrocytes in culture produce a mechanically functional tissue. J Orthop Res. 1998, 16: 227-236. 10.1002/jor.1100160210.CrossRefPubMed Fedewa MM, Oegema TR, Schwartz MH, MacLeod A, Lewis JL: Chondrocytes in culture produce a mechanically functional tissue. J Orthop Res. 1998, 16: 227-236. 10.1002/jor.1100160210.CrossRefPubMed
11.
go back to reference Andreas K, Lübke C, Häupl T, Dehne T, Morawietz L, Ringe J, Kaps C, Sittinger M: Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitro study. Arthritis Res Ther. 2008, 10: R9-10.1186/ar2358.PubMedCentralCrossRefPubMed Andreas K, Lübke C, Häupl T, Dehne T, Morawietz L, Ringe J, Kaps C, Sittinger M: Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitro study. Arthritis Res Ther. 2008, 10: R9-10.1186/ar2358.PubMedCentralCrossRefPubMed
12.
go back to reference Ibold Y, Frauenschuh S, Kaps C, Sittinger M, Ringe J, Goetz PM: Development of a high-throughput screening assay based on the 3-dimensional pannus model for rheumatoid arthritis. J Biomol Screen. 2007, 12: 956-965. 10.1177/1087057107307147.CrossRefPubMed Ibold Y, Frauenschuh S, Kaps C, Sittinger M, Ringe J, Goetz PM: Development of a high-throughput screening assay based on the 3-dimensional pannus model for rheumatoid arthritis. J Biomol Screen. 2007, 12: 956-965. 10.1177/1087057107307147.CrossRefPubMed
13.
go back to reference Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994, 331: 889-895. 10.1056/NEJM199410063311401.CrossRefPubMed Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994, 331: 889-895. 10.1056/NEJM199410063311401.CrossRefPubMed
14.
go back to reference Micheli LJ, Browne JE, Erggelet C, Fu F, Mandelbaum B, Moseley JB, Zurakowski D: Autologous chondrocyte implantation of the knee: multicenter experience and minimum 3-year follow-up. Clin J Sport Med. 2001, 11: 223-228. 10.1097/00042752-200110000-00003.CrossRefPubMed Micheli LJ, Browne JE, Erggelet C, Fu F, Mandelbaum B, Moseley JB, Zurakowski D: Autologous chondrocyte implantation of the knee: multicenter experience and minimum 3-year follow-up. Clin J Sport Med. 2001, 11: 223-228. 10.1097/00042752-200110000-00003.CrossRefPubMed
15.
go back to reference Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A: Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000, 374: 212-234. 10.1097/00003086-200005000-00020.CrossRefPubMed Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A: Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000, 374: 212-234. 10.1097/00003086-200005000-00020.CrossRefPubMed
16.
go back to reference Roberts S, McCall IW, Darby AJ, Menage J, Evans H, Harrison PE, Richardson JB: Autologous chondrocyte implantation for cartilage repair: monitoring its success by magnetic resonance imaging and histology. Arthritis Res Ther. 2003, 5: R60-73. 10.1186/ar613.PubMedCentralCrossRefPubMed Roberts S, McCall IW, Darby AJ, Menage J, Evans H, Harrison PE, Richardson JB: Autologous chondrocyte implantation for cartilage repair: monitoring its success by magnetic resonance imaging and histology. Arthritis Res Ther. 2003, 5: R60-73. 10.1186/ar613.PubMedCentralCrossRefPubMed
17.
go back to reference Steinwachs M, Kreuz PC: Autologous chondrocyte implantation in chondral defects of the knee with a type I/III collagen membrane: a prospective study with a 3-year follow-up. Arthroscopy. 2007, 23: 381-387.CrossRefPubMed Steinwachs M, Kreuz PC: Autologous chondrocyte implantation in chondral defects of the knee with a type I/III collagen membrane: a prospective study with a 3-year follow-up. Arthroscopy. 2007, 23: 381-387.CrossRefPubMed
18.
go back to reference Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O: A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am. 2007, 89: 2105-2112. 10.2106/JBJS.G.00003.CrossRefPubMed Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O: A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am. 2007, 89: 2105-2112. 10.2106/JBJS.G.00003.CrossRefPubMed
19.
go back to reference Saris DB, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, Vandekerckhove B, Almqvist KF, Claes T, Handelberg F, Lagae K, Bauwhede van der J, Vandenneucker H, Yang KG, Jelic M, Verdonk R, Veulemans N, Bellemans J, Luyten FP: Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med. 2008, 36: 235-246. 10.1177/0363546507311095.CrossRefPubMed Saris DB, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, Vandekerckhove B, Almqvist KF, Claes T, Handelberg F, Lagae K, Bauwhede van der J, Vandenneucker H, Yang KG, Jelic M, Verdonk R, Veulemans N, Bellemans J, Luyten FP: Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med. 2008, 36: 235-246. 10.1177/0363546507311095.CrossRefPubMed
20.
go back to reference Behrens P, Bitter T, Kurz B, Russlies M: Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI) – 5-year follow-up. Knee. 2006, 13: 194-202. 10.1016/j.knee.2006.02.012.CrossRefPubMed Behrens P, Bitter T, Kurz B, Russlies M: Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI) – 5-year follow-up. Knee. 2006, 13: 194-202. 10.1016/j.knee.2006.02.012.CrossRefPubMed
21.
go back to reference Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzini L, Rosa D, Sacchetti GL, Stefani G, Zanasi S: Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res. 2005, 96-105. 10.1097/01.blo.0000165737.87628.5b. 435 Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzini L, Rosa D, Sacchetti GL, Stefani G, Zanasi S: Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res. 2005, 96-105. 10.1097/01.blo.0000165737.87628.5b. 435
22.
go back to reference Erggelet C, Sittinger M, Lahm A: The arthroscopic implantation of autologous chondrocytes for the treatment of full-thickness cartilage defects of the knee joint. Arthroscopy. 2003, 19: 108-110.CrossRefPubMed Erggelet C, Sittinger M, Lahm A: The arthroscopic implantation of autologous chondrocytes for the treatment of full-thickness cartilage defects of the knee joint. Arthroscopy. 2003, 19: 108-110.CrossRefPubMed
23.
go back to reference Drobnic M, Radosavljevic D, Ravnik D, Pavlovcic V, Hribernik M: Comparison of four techniques for the fixation of a collagen scaffold in the human cadaveric knee. Osteoarthritis Cartilage. 2006, 14: 337-344. 10.1016/j.joca.2005.11.007.CrossRefPubMed Drobnic M, Radosavljevic D, Ravnik D, Pavlovcic V, Hribernik M: Comparison of four techniques for the fixation of a collagen scaffold in the human cadaveric knee. Osteoarthritis Cartilage. 2006, 14: 337-344. 10.1016/j.joca.2005.11.007.CrossRefPubMed
24.
go back to reference Bartlett W, Skinner JA, Gooding CR, Carrington RW, Flanagan AM, Briggs TW, Bentley G: Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. J Bone Joint Surg Br. 2005, 87: 640-645. 10.1302/0301-620X.87B5.15905.CrossRefPubMed Bartlett W, Skinner JA, Gooding CR, Carrington RW, Flanagan AM, Briggs TW, Bentley G: Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. J Bone Joint Surg Br. 2005, 87: 640-645. 10.1302/0301-620X.87B5.15905.CrossRefPubMed
25.
go back to reference Mark von der K, Kirsch T, Nerlich A, Kuss A, Weseloh G, Gluckert K, Stoss H: Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum. 1992, 35: 806-811. 10.1002/art.1780350715.CrossRefPubMed Mark von der K, Kirsch T, Nerlich A, Kuss A, Weseloh G, Gluckert K, Stoss H: Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum. 1992, 35: 806-811. 10.1002/art.1780350715.CrossRefPubMed
26.
go back to reference Aigner T, Bertling W, Stoss H, Weseloh G, Mark von der K: Independent expression of fibril-forming collagens I, II, and III in chondrocytes of human osteoarthritic cartilage. J Clin Invest. 1993, 91: 829-837. 10.1172/JCI116303.PubMedCentralCrossRefPubMed Aigner T, Bertling W, Stoss H, Weseloh G, Mark von der K: Independent expression of fibril-forming collagens I, II, and III in chondrocytes of human osteoarthritic cartilage. J Clin Invest. 1993, 91: 829-837. 10.1172/JCI116303.PubMedCentralCrossRefPubMed
27.
go back to reference Dehne T, Karlsson C, Ringe J, Lindahl A, Sittinger M: Gene expression profiling of HYAFF-11 cartilage transplants generated by chondrocytes from OA donors [abstract]. Tissue Eng Part A. 2008, 14: 737- Dehne T, Karlsson C, Ringe J, Lindahl A, Sittinger M: Gene expression profiling of HYAFF-11 cartilage transplants generated by chondrocytes from OA donors [abstract]. Tissue Eng Part A. 2008, 14: 737-
28.
go back to reference Stevens MM, George JH: Exploring and engineering the cell surface interface. Science. 2005, 310: 1135-1138. 10.1126/science.1106587.CrossRefPubMed Stevens MM, George JH: Exploring and engineering the cell surface interface. Science. 2005, 310: 1135-1138. 10.1126/science.1106587.CrossRefPubMed
29.
go back to reference Teo WE, He W, Ramakrishna S: Electrospun scaffold tailored for tissue-specific extracellular matrix. Biotechnol J. 2006, 1: 918-929. 10.1002/biot.200600044.CrossRefPubMed Teo WE, He W, Ramakrishna S: Electrospun scaffold tailored for tissue-specific extracellular matrix. Biotechnol J. 2006, 1: 918-929. 10.1002/biot.200600044.CrossRefPubMed
30.
go back to reference Sohier J, Moroni L, van Blitterswijk C, de Groot K, Bezemer JM: Critical factors in the design of growth factor releasing scaffolds for cartilage tissue engineering. Expert Opin Drug Deliv. 2008, 5: 543-566. 10.1517/17425247.5.5.543.CrossRefPubMed Sohier J, Moroni L, van Blitterswijk C, de Groot K, Bezemer JM: Critical factors in the design of growth factor releasing scaffolds for cartilage tissue engineering. Expert Opin Drug Deliv. 2008, 5: 543-566. 10.1517/17425247.5.5.543.CrossRefPubMed
31.
32.
go back to reference Kuo CK, Li WJ, Mauck RL, Tuan RS: Cartilage tissue engineering: its potential and uses. Curr Opin Rheumatol. 2006, 18: 64-73. 10.1097/01.bor.0000198005.88568.df.CrossRefPubMed Kuo CK, Li WJ, Mauck RL, Tuan RS: Cartilage tissue engineering: its potential and uses. Curr Opin Rheumatol. 2006, 18: 64-73. 10.1097/01.bor.0000198005.88568.df.CrossRefPubMed
33.
go back to reference Murphy JM, Dixon K, Beck S, Fabian D, Feldman A, Barry F: Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum. 2002, 46: 704-713. 10.1002/art.10118.CrossRefPubMed Murphy JM, Dixon K, Beck S, Fabian D, Feldman A, Barry F: Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum. 2002, 46: 704-713. 10.1002/art.10118.CrossRefPubMed
34.
go back to reference Scharstuhl A, Schewe B, Benz K, Gaissmaier C, Buhring HJ, Stoop R: Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology. Stem Cells. 2007, 25: 3244-3251. 10.1634/stemcells.2007-0300.CrossRefPubMed Scharstuhl A, Schewe B, Benz K, Gaissmaier C, Buhring HJ, Stoop R: Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology. Stem Cells. 2007, 25: 3244-3251. 10.1634/stemcells.2007-0300.CrossRefPubMed
35.
go back to reference Kafienah W, Mistry S, Dickinson SC, Sims TJ, Learmonth I, Hollander AP: Three-dimensional cartilage tissue engineering using adult stem cells from osteoarthritis patients. Arthritis Rheum. 2007, 56: 177-187. 10.1002/art.22285.CrossRefPubMed Kafienah W, Mistry S, Dickinson SC, Sims TJ, Learmonth I, Hollander AP: Three-dimensional cartilage tissue engineering using adult stem cells from osteoarthritis patients. Arthritis Rheum. 2007, 56: 177-187. 10.1002/art.22285.CrossRefPubMed
36.
go back to reference Eder J, Dehne T, Perka C, Ringe J, Sittinger M: Towards in situ tissue repair of osteoarthritis: differentiation and migration potential of patient-derived mesenchymal stem cells [abstract]. Tissue Eng Part A. 2008, 14: 923- Eder J, Dehne T, Perka C, Ringe J, Sittinger M: Towards in situ tissue repair of osteoarthritis: differentiation and migration potential of patient-derived mesenchymal stem cells [abstract]. Tissue Eng Part A. 2008, 14: 923-
37.
go back to reference Murphy JM, Fink DJ, Hunziker EB, Barry FP: Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003, 48: 3464-3474. 10.1002/art.11365.CrossRefPubMed Murphy JM, Fink DJ, Hunziker EB, Barry FP: Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003, 48: 3464-3474. 10.1002/art.11365.CrossRefPubMed
39.
go back to reference Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D: Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008, 11: 343-353.PubMed Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D: Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008, 11: 343-353.PubMed
40.
go back to reference Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M: Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002, 10: 199-206. 10.1053/joca.2001.0504.CrossRefPubMed Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M: Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002, 10: 199-206. 10.1053/joca.2001.0504.CrossRefPubMed
41.
go back to reference Wakitani S, Nawata M, Tensho K, Okabe T, Machida H, Ohgushi H: Repair of articular cartilage defects in the patellofemoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med. 2007, 1: 74-79. 10.1002/term.8.CrossRefPubMed Wakitani S, Nawata M, Tensho K, Okabe T, Machida H, Ohgushi H: Repair of articular cartilage defects in the patellofemoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med. 2007, 1: 74-79. 10.1002/term.8.CrossRefPubMed
42.
go back to reference Marcacci M, Kon E, Moukhachev V, Lavroukov A, Kutepov S, Quarto R, Mastrogiacomo M, Cancedda R: Stem cells associated with macroporous bioceramics for long bone repair: 6-to 7-year outcome of a pilot clinical study. Tissue Eng. 2007, 13: 947-955. 10.1089/ten.2006.0271.CrossRefPubMed Marcacci M, Kon E, Moukhachev V, Lavroukov A, Kutepov S, Quarto R, Mastrogiacomo M, Cancedda R: Stem cells associated with macroporous bioceramics for long bone repair: 6-to 7-year outcome of a pilot clinical study. Tissue Eng. 2007, 13: 947-955. 10.1089/ten.2006.0271.CrossRefPubMed
43.
go back to reference Tanaka T, Komaki H, Chazono M, Fujii K: Use of a biphasic graft constructed with chondrocytes overlying a beta-tricalcium phosphate block in the treatment of rabbit osteochondral defects. Tissue Eng. 2005, 11: 331-339. 10.1089/ten.2005.11.331.CrossRefPubMed Tanaka T, Komaki H, Chazono M, Fujii K: Use of a biphasic graft constructed with chondrocytes overlying a beta-tricalcium phosphate block in the treatment of rabbit osteochondral defects. Tissue Eng. 2005, 11: 331-339. 10.1089/ten.2005.11.331.CrossRefPubMed
44.
go back to reference Ringe J, Häupl T, Sittinger M: Future of tissue engineering in rheumatic diseases. Expert Opin Biol Ther. 2007, 7: 283-287. 10.1517/14712598.7.3.283.CrossRefPubMed Ringe J, Häupl T, Sittinger M: Future of tissue engineering in rheumatic diseases. Expert Opin Biol Ther. 2007, 7: 283-287. 10.1517/14712598.7.3.283.CrossRefPubMed
45.
go back to reference Chamberlain G, Fox J, Ashton B, Middleton J: Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007, 25: 2739-2749. 10.1634/stemcells.2007-0197.CrossRefPubMed Chamberlain G, Fox J, Ashton B, Middleton J: Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007, 25: 2739-2749. 10.1634/stemcells.2007-0197.CrossRefPubMed
46.
go back to reference Erggelet C, Neumann K, Endres M, Haberstroh K, Sittinger M, Kaps C: Regeneration of ovine articular cartilage defects by cell-free polymer-based implants. Biomaterials. 2007, 28: 5570-5580. 10.1016/j.biomaterials.2007.09.005.CrossRefPubMed Erggelet C, Neumann K, Endres M, Haberstroh K, Sittinger M, Kaps C: Regeneration of ovine articular cartilage defects by cell-free polymer-based implants. Biomaterials. 2007, 28: 5570-5580. 10.1016/j.biomaterials.2007.09.005.CrossRefPubMed
48.
go back to reference Ringe J, Strassburg S, Neumann K, Endres M, Notter M, Burmester GR, Kaps C, Sittinger M: Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2. J Cell Biochem. 2007, 101: 135-146. 10.1002/jcb.21172.CrossRefPubMed Ringe J, Strassburg S, Neumann K, Endres M, Notter M, Burmester GR, Kaps C, Sittinger M: Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2. J Cell Biochem. 2007, 101: 135-146. 10.1002/jcb.21172.CrossRefPubMed
49.
go back to reference Fiedler J, Roderer G, Gunther KP, Brenner RE: BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. J Cell Biochem. 2002, 87: 305-312. 10.1002/jcb.10309.CrossRefPubMed Fiedler J, Roderer G, Gunther KP, Brenner RE: BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. J Cell Biochem. 2002, 87: 305-312. 10.1002/jcb.10309.CrossRefPubMed
50.
go back to reference Endres M, Neumann K, Häupl T, Erggelet C, Ringe J, Sittinger M, Kaps C: Synovial fluid recruits human mesenchymal progenitors from subchondral spongious bone marrow. J Orthop Res. 2007, 25: 1299-1307. 10.1002/jor.20394.CrossRefPubMed Endres M, Neumann K, Häupl T, Erggelet C, Ringe J, Sittinger M, Kaps C: Synovial fluid recruits human mesenchymal progenitors from subchondral spongious bone marrow. J Orthop Res. 2007, 25: 1299-1307. 10.1002/jor.20394.CrossRefPubMed
52.
go back to reference Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R: Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002, 30: 42-48. 10.1016/S0301-472X(01)00769-X.CrossRefPubMed Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R: Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002, 30: 42-48. 10.1016/S0301-472X(01)00769-X.CrossRefPubMed
53.
go back to reference Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, Giunti D, Ceravolo A, Cazzanti F, Frassoni F, Mancardi G, Uccelli A: Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. 2005, 106: 1755-1761. 10.1182/blood-2005-04-1496.CrossRefPubMed Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, Giunti D, Ceravolo A, Cazzanti F, Frassoni F, Mancardi G, Uccelli A: Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. 2005, 106: 1755-1761. 10.1182/blood-2005-04-1496.CrossRefPubMed
54.
go back to reference Augello A, Tasso R, Negrini SM, Cancedda R, Pennesi G: Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum. 2007, 56: 1175-1186. 10.1002/art.22511.CrossRefPubMed Augello A, Tasso R, Negrini SM, Cancedda R, Pennesi G: Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum. 2007, 56: 1175-1186. 10.1002/art.22511.CrossRefPubMed
55.
go back to reference Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE: Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood. 2006, 108: 2114-2120. 10.1182/blood-2005-11-011650.PubMedCentralCrossRefPubMed Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE: Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood. 2006, 108: 2114-2120. 10.1182/blood-2005-11-011650.PubMedCentralCrossRefPubMed
56.
go back to reference Sudres M, Norol F, Trenado A, Grégoire S, Charlotte F, Levacher B, Lataillade JJ, Bourin P, Holy X, Vernant JP, Klatzmann D, Cohen JL: Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J Immunol. 2006, 176: 7761-7767.CrossRefPubMed Sudres M, Norol F, Trenado A, Grégoire S, Charlotte F, Levacher B, Lataillade JJ, Bourin P, Holy X, Vernant JP, Klatzmann D, Cohen JL: Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J Immunol. 2006, 176: 7761-7767.CrossRefPubMed
57.
go back to reference Djouad F, Fritz V, Apparailly F, Louis-Plence P, Bony C, Sany J, Jorgensen C, Noel D: Reversal of the immunosuppressive properties of mesenchymal stem cells by tumor necrosis factor alpha in collagen-induced arthritis. Arthritis Rheum. 2005, 52: 1595-1603. 10.1002/art.21012.CrossRefPubMed Djouad F, Fritz V, Apparailly F, Louis-Plence P, Bony C, Sany J, Jorgensen C, Noel D: Reversal of the immunosuppressive properties of mesenchymal stem cells by tumor necrosis factor alpha in collagen-induced arthritis. Arthritis Rheum. 2005, 52: 1595-1603. 10.1002/art.21012.CrossRefPubMed
58.
go back to reference Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringdén O, Developmental Committee of the European Group for Blood and Marrow Transplantation: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008, 371: 1579-1586. 10.1016/S0140-6736(08)60690-X.CrossRefPubMed Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringdén O, Developmental Committee of the European Group for Blood and Marrow Transplantation: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008, 371: 1579-1586. 10.1016/S0140-6736(08)60690-X.CrossRefPubMed
59.
go back to reference Papadaki HA, Marsh JC, Eliopoulos GD: Bone marrow stem cells and stromal cells in autoimmune cytopenias. Leuk Lymphoma. 2002, 43: 753-760. 10.1080/10428190290016854.CrossRefPubMed Papadaki HA, Marsh JC, Eliopoulos GD: Bone marrow stem cells and stromal cells in autoimmune cytopenias. Leuk Lymphoma. 2002, 43: 753-760. 10.1080/10428190290016854.CrossRefPubMed
60.
go back to reference Kastrinaki MC, Sidiropoulos P, Roche S, Ringe J, Lehmann S, Kritikos H, Vlahava VM, Delorme B, Eliopoulos GD, Jorgensen C, Charbord P, Häupl T, Boumpas DT, Papadaki HA: Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis. Ann Rheum Dis. 2008, 67: 741-749. 10.1136/ard.2007.076174.CrossRefPubMed Kastrinaki MC, Sidiropoulos P, Roche S, Ringe J, Lehmann S, Kritikos H, Vlahava VM, Delorme B, Eliopoulos GD, Jorgensen C, Charbord P, Häupl T, Boumpas DT, Papadaki HA: Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis. Ann Rheum Dis. 2008, 67: 741-749. 10.1136/ard.2007.076174.CrossRefPubMed
61.
go back to reference Del Papa N, Quirici N, Soligo D, Scavullo C, Cortiana M, Borsotti C, Maglione W, Comina DP, Vitali C, Fraticelli P, Gabrielli A, Cortelezzi A, Lambertenghi-Deliliers G: Bone marrow endothelial progenitors are defective in systemic sclerosis. Arthritis Rheum. 2006, 54: 2605-2615. 10.1002/art.22035.CrossRefPubMed Del Papa N, Quirici N, Soligo D, Scavullo C, Cortiana M, Borsotti C, Maglione W, Comina DP, Vitali C, Fraticelli P, Gabrielli A, Cortelezzi A, Lambertenghi-Deliliers G: Bone marrow endothelial progenitors are defective in systemic sclerosis. Arthritis Rheum. 2006, 54: 2605-2615. 10.1002/art.22035.CrossRefPubMed
62.
go back to reference Bocelli-Tyndall C, Bracci L, Spagnoli G, Braccini A, Bouchenaki M, Ceredig R, Pistoia V, Martin I, Tyndall A: Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and autoimmune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro. Rheumatology (Oxford). 2007, 46: 403-408. 10.1093/rheumatology/kel267.CrossRef Bocelli-Tyndall C, Bracci L, Spagnoli G, Braccini A, Bouchenaki M, Ceredig R, Pistoia V, Martin I, Tyndall A: Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and autoimmune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro. Rheumatology (Oxford). 2007, 46: 403-408. 10.1093/rheumatology/kel267.CrossRef
63.
go back to reference Kwan MD, Slater BJ, Wan DC, Longaker MT: Cell-based therapies for skeletal regenerative medicine. Hum Mol Genet. 2008, 17: R93-98. 10.1093/hmg/ddn071.CrossRefPubMed Kwan MD, Slater BJ, Wan DC, Longaker MT: Cell-based therapies for skeletal regenerative medicine. Hum Mol Genet. 2008, 17: R93-98. 10.1093/hmg/ddn071.CrossRefPubMed
64.
go back to reference Fickert S, Fiedler J, Brenner RE: Identification of subpopulations with characteristics of mesenchymal progenitor cells from human osteoarthritic cartilage using triple staining for cell surface markers. Arthritis Res Ther. 2004, 6: R422-432. 10.1186/ar1210.PubMedCentralCrossRefPubMed Fickert S, Fiedler J, Brenner RE: Identification of subpopulations with characteristics of mesenchymal progenitor cells from human osteoarthritic cartilage using triple staining for cell surface markers. Arthritis Res Ther. 2004, 6: R422-432. 10.1186/ar1210.PubMedCentralCrossRefPubMed
65.
go back to reference Pei M, He F, Vunjak-Novakovic G: Synovium-derived stem cell-based chondrogenesis. Differentiation. 2008, 76: 1044-1056. 10.1111/j.1432-0436.2008.00299.x.PubMedCentralCrossRefPubMed Pei M, He F, Vunjak-Novakovic G: Synovium-derived stem cell-based chondrogenesis. Differentiation. 2008, 76: 1044-1056. 10.1111/j.1432-0436.2008.00299.x.PubMedCentralCrossRefPubMed
66.
go back to reference De Bari C, Dell'Accio F, Luyten FP: Failure of in vitro-differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo. Arthritis Rheum. 2004, 50: 142-150. 10.1002/art.11450.CrossRefPubMed De Bari C, Dell'Accio F, Luyten FP: Failure of in vitro-differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo. Arthritis Rheum. 2004, 50: 142-150. 10.1002/art.11450.CrossRefPubMed
67.
go back to reference Bielby RC, Boccaccini AR, Polak JM, Buttery LD: In vitro differentiation and in vivo mineralization of osteogenic cells derived from human embryonic stem cells. Tissue Eng. 2004, 10: 1518-1525.CrossRefPubMed Bielby RC, Boccaccini AR, Polak JM, Buttery LD: In vitro differentiation and in vivo mineralization of osteogenic cells derived from human embryonic stem cells. Tissue Eng. 2004, 10: 1518-1525.CrossRefPubMed
68.
go back to reference Wakitani S, Aoki H, Harada Y, Sonobe M, Morita Y, Mu Y, Tomita N, Nakamura Y, Takeda S, Watanabe TK, Tanigami A: Embryonic stem cells form articular cartilage, not teratomas, in osteochondral defects of rat joints. Cell Transplant. 2004, 13: 331-336. 10.3727/000000004783983891.CrossRefPubMed Wakitani S, Aoki H, Harada Y, Sonobe M, Morita Y, Mu Y, Tomita N, Nakamura Y, Takeda S, Watanabe TK, Tanigami A: Embryonic stem cells form articular cartilage, not teratomas, in osteochondral defects of rat joints. Cell Transplant. 2004, 13: 331-336. 10.3727/000000004783983891.CrossRefPubMed
69.
go back to reference Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007, 131: 861-872. 10.1016/j.cell.2007.11.019.CrossRefPubMed Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007, 131: 861-872. 10.1016/j.cell.2007.11.019.CrossRefPubMed
70.
go back to reference Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA: Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007, 318: 1917-1920. 10.1126/science.1151526.CrossRefPubMed Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA: Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007, 318: 1917-1920. 10.1126/science.1151526.CrossRefPubMed
71.
go back to reference Zhang Z, McCaffery JM, Spencer RG, Francomano CA: Hyaline cartilage engineered by chondrocytes in pellet culture: histological, immunohistochemical and ultrastructural analysis in comparison with cartilage explants. J Anat. 2004, 205: 229-237. 10.1111/j.0021-8782.2004.00327.x.PubMedCentralCrossRefPubMed Zhang Z, McCaffery JM, Spencer RG, Francomano CA: Hyaline cartilage engineered by chondrocytes in pellet culture: histological, immunohistochemical and ultrastructural analysis in comparison with cartilage explants. J Anat. 2004, 205: 229-237. 10.1111/j.0021-8782.2004.00327.x.PubMedCentralCrossRefPubMed
72.
go back to reference Bonaventure J, Kadhom N, Cohen-Solal L, Ng KH, Bourguignon J, Lasselin C, Freisinger P: Reexpression of cartilage-specific genes by dedifferentiated human articular chondrocytes cultured in alginate beads. Exp Cell Res. 1994, 212: 97-104. 10.1006/excr.1994.1123.CrossRefPubMed Bonaventure J, Kadhom N, Cohen-Solal L, Ng KH, Bourguignon J, Lasselin C, Freisinger P: Reexpression of cartilage-specific genes by dedifferentiated human articular chondrocytes cultured in alginate beads. Exp Cell Res. 1994, 212: 97-104. 10.1006/excr.1994.1123.CrossRefPubMed
73.
go back to reference Lemare F, Steimberg N, Le Griel C, Demignot S, Adolphe M: Dedifferentiated chondrocytes cultured in alginate beads: restoration of the differentiated phenotype and of the metabolic responses to interleukin-1beta. J Cell Physiol. 1998, 176: 303-313. 10.1002/(SICI)1097-4652(199808)176:2<303::AID-JCP8>3.0.CO;2-S.CrossRefPubMed Lemare F, Steimberg N, Le Griel C, Demignot S, Adolphe M: Dedifferentiated chondrocytes cultured in alginate beads: restoration of the differentiated phenotype and of the metabolic responses to interleukin-1beta. J Cell Physiol. 1998, 176: 303-313. 10.1002/(SICI)1097-4652(199808)176:2<303::AID-JCP8>3.0.CO;2-S.CrossRefPubMed
74.
go back to reference Häupl T, Yahyawi M, Lübke C, Ringe J, Rohrlach T, Burmester GR, Sittinger M, Kaps C: Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007, 12: 328-340. 10.1177/1087057107299261.CrossRefPubMed Häupl T, Yahyawi M, Lübke C, Ringe J, Rohrlach T, Burmester GR, Sittinger M, Kaps C: Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007, 12: 328-340. 10.1177/1087057107299261.CrossRefPubMed
75.
go back to reference Huber LC, Distler O, Tarner I, Gay RE, Gay S, Pap T: Synovial fibroblasts: key players in rheumatoid arthritis. Rheumatology (Oxford). 2006, 45: 669-675. 10.1093/rheumatology/kel065.CrossRef Huber LC, Distler O, Tarner I, Gay RE, Gay S, Pap T: Synovial fibroblasts: key players in rheumatoid arthritis. Rheumatology (Oxford). 2006, 45: 669-675. 10.1093/rheumatology/kel065.CrossRef
76.
go back to reference Lübke C, Ringe J, Krenn V, Fernahl G, Pelz S, Kreusch-Brinker R, Sittinger M, Paulitschke M: Growth characterization of neo porcine cartilage pellets and their use in an interactive culture model. Osteoarthritis Cartilage. 2005, 13: 478-487. 10.1016/j.joca.2004.01.009.CrossRefPubMed Lübke C, Ringe J, Krenn V, Fernahl G, Pelz S, Kreusch-Brinker R, Sittinger M, Paulitschke M: Growth characterization of neo porcine cartilage pellets and their use in an interactive culture model. Osteoarthritis Cartilage. 2005, 13: 478-487. 10.1016/j.joca.2004.01.009.CrossRefPubMed
77.
go back to reference Lübke C, Andreas K, Yahyawi M, Krenn V, Morawietz L, Ringe J, Burmester GR, Häupl T, Kaps C, Sittinger M: Gene expression profiling of an in vitro tissue model for cartilage destruction [abstract]. Altex. 2006, 23: 113-http://www.altex.ch/resources/AbstractsLinz20064.pdf. Lübke C, Andreas K, Yahyawi M, Krenn V, Morawietz L, Ringe J, Burmester GR, Häupl T, Kaps C, Sittinger M: Gene expression profiling of an in vitro tissue model for cartilage destruction [abstract]. Altex. 2006, 23: 113-http://​www.​altex.​ch/​resources/​AbstractsLinz200​64.​pdf.​
Metadata
Title
Tissue engineering in the rheumatic diseases
Authors
Jochen Ringe
Michael Sittinger
Publication date
01-02-2009
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2009
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2572

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