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Published in: Knee Surgery, Sports Traumatology, Arthroscopy 6/2014

01-06-2014 | Experimental Study

Cartilage repair using mesenchymal stem cell (MSC) sheet and MSCs-loaded bilayer PLGA scaffold in a rabbit model

Authors: Yiying Qi, Yi Du, Weixu Li, Xuesong Dai, Tengfei Zhao, Weiqi Yan

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 6/2014

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Abstract

Purpose

The integration of regenerated cartilage with surrounding native cartilage is a major challenge for the success of cartilage tissue-engineering strategies. The purpose of this study is to investigate whether incorporation of the power of mesenchymal stem cell (MSC) sheet to MSCs-loaded bilayer poly-(lactic-co-glycolic acid) (PLGA) scaffolds can improve the integration and repair of cartilage defects in a rabbit model.

Methods

Rabbit bone marrow-derived MSCs were cultured and formed cell sheet. Full-thickness cylindrical osteochondral defects (4 mm in diameter, 3 mm in depth) were created in the patellar groove of 18 New Zealand white rabbits and the osteochondral defects were treated with PLGA scaffold (n = 6), PLGA/MSCs (n = 6) or MSC sheet-encapsulated PLGA/MSCs (n = 6). After 6 and 12 weeks, the integration and tissue response were evaluated histologically.

Results

The MSC sheet-encapsulated PLGA/MCSs group showed significantly more amounts of hyaline cartilage and higher histological scores than PLGA/MSCs group and PLGA group (P < 0.05). In addition, the MSC sheet-encapsulated PLGA/MCSs group showed the best integration between the repaired cartilage and surrounding normal cartilage and subchondral bone compared to other two groups.

Conclusions

The novel method of incorporation of MSC sheet to PLGA/MCSs could enhance the ability of cartilage regeneration and integration between repair cartilage and the surrounding cartilage. Transplantation of autologous MSC sheet combined with traditional strategies or cartilage debris might provide therapeutic opportunities for improving cartilage regeneration and integration in humans.
Literature
1.
go back to reference Ahsan T, Lottman LM, Harwood F, Amiel D, Sah RL (1999) Integrative cartilage repair: inhibition by beta-aminopropionitrile. J Orthop Res 17:850–857PubMedCrossRef Ahsan T, Lottman LM, Harwood F, Amiel D, Sah RL (1999) Integrative cartilage repair: inhibition by beta-aminopropionitrile. J Orthop Res 17:850–857PubMedCrossRef
2.
3.
go back to reference Bentley G, Greer RB 3rd (1971) Homotransplantation of isolated epiphyseal and articular cartilage chondrocytes into joint surfaces of rabbits. Nature 230:385–388PubMedCrossRef Bentley G, Greer RB 3rd (1971) Homotransplantation of isolated epiphyseal and articular cartilage chondrocytes into joint surfaces of rabbits. Nature 230:385–388PubMedCrossRef
4.
go back to reference Bos PK, DeGroot J, Budde M, Verhaar JA, van Osch GJ (2002) Specific enzymatic treatment of bovine and human articular cartilage: implications for integrative cartilage repair. Arthr Rheum 46:976–985CrossRef Bos PK, DeGroot J, Budde M, Verhaar JA, van Osch GJ (2002) Specific enzymatic treatment of bovine and human articular cartilage: implications for integrative cartilage repair. Arthr Rheum 46:976–985CrossRef
5.
go back to reference Breinan HA, Martin SD, Hsu HP, Spector M (2000) Healing of canine articular cartilage defects treated with microfracture, a type-II collagen matrix, or cultured autologous chondrocytes. J Orthop Res 18:781–789PubMedCrossRef Breinan HA, Martin SD, Hsu HP, Spector M (2000) Healing of canine articular cartilage defects treated with microfracture, a type-II collagen matrix, or cultured autologous chondrocytes. J Orthop Res 18:781–789PubMedCrossRef
6.
go back to reference Brittberg M, Tallheden T, Sjogren-Jansson B, Lindahl A, Peterson L (2001) Autologous chondrocytes used for articular cartilage repair: an update. Clin Orthop Relat Res 391(suppl):S337–S348PubMedCrossRef Brittberg M, Tallheden T, Sjogren-Jansson B, Lindahl A, Peterson L (2001) Autologous chondrocytes used for articular cartilage repair: an update. Clin Orthop Relat Res 391(suppl):S337–S348PubMedCrossRef
7.
go back to reference Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084PubMedCrossRef Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084PubMedCrossRef
8.
go back to reference Chen FH, Tuan RS (2008) Mesenchymal stem cells in arthritic diseases. Arthr Res Ther 10:223CrossRef Chen FH, Tuan RS (2008) Mesenchymal stem cells in arthritic diseases. Arthr Res Ther 10:223CrossRef
9.
go back to reference Chen X, Armstrong MA, Li G (2006) Mesenchymal stem cells in immunoregulation. Immunol Cell Biol 84:413–421PubMedCrossRef Chen X, Armstrong MA, Li G (2006) Mesenchymal stem cells in immunoregulation. Immunol Cell Biol 84:413–421PubMedCrossRef
10.
go back to reference Chu CR, Coutts RD, Yoshioka M, Harwood FL, Monosov AZ, Amiel D (1995) Articular cartilage repair using allogeneic perichondrocyte-seeded biodegradable porous polylactic acid (PLA): a tissue-engineering study. J Biomed Mater Res 29:1147–1154PubMedCrossRef Chu CR, Coutts RD, Yoshioka M, Harwood FL, Monosov AZ, Amiel D (1995) Articular cartilage repair using allogeneic perichondrocyte-seeded biodegradable porous polylactic acid (PLA): a tissue-engineering study. J Biomed Mater Res 29:1147–1154PubMedCrossRef
11.
go back to reference Chu CR, Dounchis JS, Yoshioka M, Sah RL, Coutts RD, Amiel D (1997) Osteochondral repair using perichondrial cells. A 1 year study in rabbits. Clin Orthop Relat Res 340:220–229PubMedCrossRef Chu CR, Dounchis JS, Yoshioka M, Sah RL, Coutts RD, Amiel D (1997) Osteochondral repair using perichondrial cells. A 1 year study in rabbits. Clin Orthop Relat Res 340:220–229PubMedCrossRef
12.
go back to reference DiMicco MA, Sah RL (2001) Integrative cartilage repair: adhesive strength is correlated with collagen deposition. J Orthop Res 19:1105–1112PubMedCrossRef DiMicco MA, Sah RL (2001) Integrative cartilage repair: adhesive strength is correlated with collagen deposition. J Orthop Res 19:1105–1112PubMedCrossRef
13.
go back to reference Fan H, Hu Y, Zhang C et al (2006) Cartilage regeneration using mesenchymal stem cells and a PLGA-gelatin/chondroitin/hyaluronate hybrid scaffold. Biomaterials 27:4573–4580PubMedCrossRef Fan H, Hu Y, Zhang C et al (2006) Cartilage regeneration using mesenchymal stem cells and a PLGA-gelatin/chondroitin/hyaluronate hybrid scaffold. Biomaterials 27:4573–4580PubMedCrossRef
14.
go back to reference Gross AE, Kim W, Las Heras F, Backstein D, Safir O, Pritzker KP (2008) Fresh osteochondral allograft for posttraumatic knee defects: long-term followup. Clin Orthop Relat Res 466:1863–1870PubMedCentralPubMedCrossRef Gross AE, Kim W, Las Heras F, Backstein D, Safir O, Pritzker KP (2008) Fresh osteochondral allograft for posttraumatic knee defects: long-term followup. Clin Orthop Relat Res 466:1863–1870PubMedCentralPubMedCrossRef
15.
go back to reference Ho ST, Hutmacher DW, Ekaputra AK, Hitendra D, Hui JH (2010) The evaluation of a biphasic osteochondral implant coupled with an electro spun membrane in a large animal model. Tissue Eng Part A 16:1123–1141PubMedCrossRef Ho ST, Hutmacher DW, Ekaputra AK, Hitendra D, Hui JH (2010) The evaluation of a biphasic osteochondral implant coupled with an electro spun membrane in a large animal model. Tissue Eng Part A 16:1123–1141PubMedCrossRef
16.
go back to reference Horas U, Pelinkovic D, Herr G, Aigner T, Schnettler R (2003) Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. a prospective, comparative trial. J Bone Joint Surg Am 85-A:185–192 Horas U, Pelinkovic D, Herr G, Aigner T, Schnettler R (2003) Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. a prospective, comparative trial. J Bone Joint Surg Am 85-A:185–192
17.
go back to reference Hunziker EB (1999) Articular cartilage repair: are the intrinsic biological constraints undermining this process insuperable? Osteoarthr Cartil 7:15–28PubMedCrossRef Hunziker EB (1999) Articular cartilage repair: are the intrinsic biological constraints undermining this process insuperable? Osteoarthr Cartil 7:15–28PubMedCrossRef
18.
go back to reference Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. a review of the current status and prospects. Osteoarthr Cartil 10:432–463PubMedCrossRef Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. a review of the current status and prospects. Osteoarthr Cartil 10:432–463PubMedCrossRef
19.
go back to reference Jiang Y, Chen LK, Zhu DC et al (2010) The inductive effect of bone morphogenetic protein-4 on chondral-lineage differentiation and in situ cartilage repair. Tissue Eng Part A 16:1621–1632PubMedCrossRef Jiang Y, Chen LK, Zhu DC et al (2010) The inductive effect of bone morphogenetic protein-4 on chondral-lineage differentiation and in situ cartilage repair. Tissue Eng Part A 16:1621–1632PubMedCrossRef
20.
go back to reference Koelling S, Miosge N (2009) Stem cell therapy for cartilage regeneration in osteoarthritis. Expert Opin Biol Ther 9(11):1399–1405PubMedCrossRef Koelling S, Miosge N (2009) Stem cell therapy for cartilage regeneration in osteoarthritis. Expert Opin Biol Ther 9(11):1399–1405PubMedCrossRef
21.
go back to reference Labbe B, Marceau-Fortier G, Fradette J (2011) Cell sheet technology for tissue engineering: the self-assembly approach using adipose-derived stromal cells. Methods Mol Biol 702:429–441PubMedCrossRef Labbe B, Marceau-Fortier G, Fradette J (2011) Cell sheet technology for tissue engineering: the self-assembly approach using adipose-derived stromal cells. Methods Mol Biol 702:429–441PubMedCrossRef
22.
go back to reference Lane JG, Massie JB, Ball ST et al (2004) Follow-up of osteochondral plug transfers in a goat model: a 6 month study. Am J Sports Med 32:1440–1450PubMedCrossRef Lane JG, Massie JB, Ball ST et al (2004) Follow-up of osteochondral plug transfers in a goat model: a 6 month study. Am J Sports Med 32:1440–1450PubMedCrossRef
23.
go back to reference Lee CS, Gleghorn JP, Won Choi N, Cabodi M, Stroock AD, Bonassar LJ (2007) Integration of layered chondrocyte-seeded alginate hydrogel scaffolds. Biomaterials 28:2987–2993PubMedCrossRef Lee CS, Gleghorn JP, Won Choi N, Cabodi M, Stroock AD, Bonassar LJ (2007) Integration of layered chondrocyte-seeded alginate hydrogel scaffolds. Biomaterials 28:2987–2993PubMedCrossRef
24.
go back to reference Levy AS, Lohnes J, Sculley S, LeCroy M, Garrett W (1996) Chondral delamination of the knee in soccer players. Am J Sports Med 24:634–639PubMedCrossRef Levy AS, Lohnes J, Sculley S, LeCroy M, Garrett W (1996) Chondral delamination of the knee in soccer players. Am J Sports Med 24:634–639PubMedCrossRef
25.
go back to reference Mainil-Varlet P, Aigner T, Brittberg M et al. (2003) Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS). J Bone Joint Surg Am 85-A(suppl 2): S45–S57 Mainil-Varlet P, Aigner T, Brittberg M et al. (2003) Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS). J Bone Joint Surg Am 85-A(suppl 2): S45–S57
26.
go back to reference Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR (2009) Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 37:2053–2063PubMedCrossRef Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR (2009) Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 37:2053–2063PubMedCrossRef
27.
go back to reference Nakamura A, Akahane M, Shigematsu H et al (2010) Cell sheet transplantation of cultured mesenchymal stem cells enhances bone formation in a rat nonunion model. Bone 46:418–424PubMedCrossRef Nakamura A, Akahane M, Shigematsu H et al (2010) Cell sheet transplantation of cultured mesenchymal stem cells enhances bone formation in a rat nonunion model. Bone 46:418–424PubMedCrossRef
28.
go back to reference Ng KW, Leong DT, Hutmacher DW (2005) The challenge to measure cell proliferation in two and three dimensions. Tissue Eng 11:182–191PubMedCrossRef Ng KW, Leong DT, Hutmacher DW (2005) The challenge to measure cell proliferation in two and three dimensions. Tissue Eng 11:182–191PubMedCrossRef
29.
go back to reference O’Driscoll SW (2001) Preclinical cartilage repair: current status and future perspectives. Clin Orthop Relat Res 391(suppl):S397–S401PubMedCrossRef O’Driscoll SW (2001) Preclinical cartilage repair: current status and future perspectives. Clin Orthop Relat Res 391(suppl):S397–S401PubMedCrossRef
30.
go back to reference Qi Y, Zhao T, Xu K, Dai T, Yan W (2012) The restoration of full-thickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model. Mol Biol Rep 39:1231–1237PubMedCrossRef Qi Y, Zhao T, Xu K, Dai T, Yan W (2012) The restoration of full-thickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model. Mol Biol Rep 39:1231–1237PubMedCrossRef
31.
go back to reference Qi YY, Chen X, Jiang YZ et al (2009) Local delivery of autologous platelet in collagen matrix simulated in situ articular cartilage repair. Cell Transpl 18:1161–1169CrossRef Qi YY, Chen X, Jiang YZ et al (2009) Local delivery of autologous platelet in collagen matrix simulated in situ articular cartilage repair. Cell Transpl 18:1161–1169CrossRef
32.
go back to reference Redman SN, Dowthwaite GP, Thomson BM, Archer CW (2004) The cellular responses of articular cartilage to sharp and blunt trauma. Osteoarthr Cartil 12:106–116PubMedCrossRef Redman SN, Dowthwaite GP, Thomson BM, Archer CW (2004) The cellular responses of articular cartilage to sharp and blunt trauma. Osteoarthr Cartil 12:106–116PubMedCrossRef
33.
go back to reference Reindel ES, Ayroso AM, Chen AC, Chun DM, Schinagl RM, Sah RL (1995) Integrative repair of articular cartilage in vitro: adhesive strength of the interface region. J Orthop Res 13:751–760PubMedCrossRef Reindel ES, Ayroso AM, Chen AC, Chun DM, Schinagl RM, Sah RL (1995) Integrative repair of articular cartilage in vitro: adhesive strength of the interface region. J Orthop Res 13:751–760PubMedCrossRef
34.
go back to reference Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG (2003) Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy 19:477–484PubMedCrossRef Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG (2003) Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy 19:477–484PubMedCrossRef
35.
go back to reference Uematsu K, Hattori K, Ishimoto Y et al (2005) Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold. Biomaterials 26:4273–4279PubMedCrossRef Uematsu K, Hattori K, Ishimoto Y et al (2005) Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold. Biomaterials 26:4273–4279PubMedCrossRef
36.
go back to reference Yang J, Yamato M, Kohno C, Nishimoto A, Sekine H, Fukai F (2005) Cell sheet engineering: recreating tissues without biodegradable scaffolds. Biomaterials 26:6415–6422PubMedCrossRef Yang J, Yamato M, Kohno C, Nishimoto A, Sekine H, Fukai F (2005) Cell sheet engineering: recreating tissues without biodegradable scaffolds. Biomaterials 26:6415–6422PubMedCrossRef
37.
go back to reference Zhang Z, McCaffery JM, Spencer RG, Francomano CA (2005) Growth and integration of neocartilage with native cartilage in vitro. J Orthop Res 23:433–439PubMedCrossRef Zhang Z, McCaffery JM, Spencer RG, Francomano CA (2005) Growth and integration of neocartilage with native cartilage in vitro. J Orthop Res 23:433–439PubMedCrossRef
38.
go back to reference Zou XH, Cai HX, Yin Z et al (2009) A novel strategy incorporated the power of mesenchymal stem cells to allografts for segmental bone tissue engineering. Cell Transpl 18:433–441CrossRef Zou XH, Cai HX, Yin Z et al (2009) A novel strategy incorporated the power of mesenchymal stem cells to allografts for segmental bone tissue engineering. Cell Transpl 18:433–441CrossRef
Metadata
Title
Cartilage repair using mesenchymal stem cell (MSC) sheet and MSCs-loaded bilayer PLGA scaffold in a rabbit model
Authors
Yiying Qi
Yi Du
Weixu Li
Xuesong Dai
Tengfei Zhao
Weiqi Yan
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 6/2014
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-012-2256-3

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