The restoration of full-thickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model

Qi, Yiying; Zhao, Tengfei; Xu, Ke; Dai, Tianyang; Yan, Wei

doi:10.1007/s11033-011-0853-8

Cited by 39 publications

(31 citation statements)

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“…However, cartilage tissue engineering systems with either cell type have been shown to be successful in some cases and to different extents in various animal models (Grässel and Anders, 2012). Although large animal models (such as pigs, goats, and horses) may more closely resemble the human system, the herein used rabbit model is one of the well accepted small animal models for evaluation of GF or cell-loaded scaffolds in cartilage defects (Sellers et al, 1997;Sellers et al, 2000;Rudert, 2002;Shao et al, 2006;Holland et al, 2007;Qi et al, 2009;Im and Lee, 2010;Jiang et al, 2010;Tokuhara et al, 2010;Wang et al, 2010;Chen et al, 2011;Qi et al, 2011;Yang et al, 2011;Qi et al, 2012;Zhang et al, 2013). Additional to the choice of an adequate animal model, there are still a number of challenges to be overcome in the search for optimum cartilage repair conditions as e.g., the recognition of the optimal cell source, scaffolds, and GFs.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, scaffolds may be loaded with GFs such as bone morphogenetic protein (BMP)-2 and TGF-b1 (Sellers et al, 1997;Sellers et al, 2000;Holland et al, 2005;Holland et al, 2007;Reyes et al, 2012), seeded with chondrocytes or MSCs Qi et al, 2011;Ito et al, 2012), or employed with combinations of both GFs and cells (Im and Lee, 2010;Wang et al, 2010). To date, only few studies compare MSCs and chondrocytes in cartilage defect repair.…”

Section: Introductionmentioning

confidence: 99%

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Comparative, osteochondral defect repair: Stem cells versus chondrocytes versus Bone Morphogenetic Protein-2, solely or in combination

Reyes

Pec²,

Sánchez³

et al. 2013

eCM

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Full-thickness articular cartilage damage does not resolve spontaneously. Studies with growth factors, implantation of autologous chondrocytes and mesenchymal stem cells have led to variable, to some extent inconsistent, results. This work compares osteochondral knee-defect repair in rabbits upon implantation of a previously described alginate/ (poly(lactic-co-glycolic) acid (PLGA) osteochondral scaffold in distinct conditions. Systems were either in vitro pre-cultured with a small number of allogeneic chondrocytes under fibroblast growth factor (FGF)-2 stimulation or the same amount of allogeneic, marrow derived, mesenchymal stem cells (without any pre-differentiation), or loaded with microsphere-encapsulated bone morphogenetic protein (BMP)-2 within the alginate layer, or holding combinations of one or the other cell type with BMP-2. The experimental limit was 12 weeks, because a foregoing study with this release system had shown a maintained tissue response for at least 24 weeks post-operation. After only 6 weeks, histological analyses revealed newly formed cartilage-like tissue, which resembled the adjacent, normal cartilage in cell as well as BMP-2 treated defects, but cell therapy gave higher histological scores. This advantage evened out until 12 weeks. Combinations of cells and BMP-2 did not result in any additive or synergistic effect. Equally efficient osteochondral defect repair was achieved with chondrocyte, stem cell, and BMP-2 treatment. Expression of collagen X and collagen I, signs of ongoing ossification, were histologically undetectable, and the presence of aggrecan protein indicated cartilage-like tissue. In conclusion, further work should demonstrate whether spatiotemporally controlled, on-site BMP-2 release alone could become a feasible therapeutic approach to repair large osteochondral defects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative, osteochondral defect repair: Stem cells versus chondrocytes versus Bone Morphogenetic Protein-2, solely or in combination

Reyes

Pec²,

Sánchez³

et al. 2013

eCM

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“…For implantation purposes in vivo, BMSC seeding densities of 1-50 × 10 6 cells/cm 3 of biomaterial matrix have been used in preclinical animal studies. 1,14,[23][24][25][26][27][28][29][30][31][32] In clinical studies, a density of 5 × 10 6 cells/cm 3 has been reported although the rationale for adopting this seeding density was not described. 3,4 The objective of this study was to assess the impact of cell seeding density within a clinically relevant, collagen I scaffold on in vitro BMSC chondrogenesis following 2D and 3D isolation and expansion.…”

Section: Introductionmentioning

confidence: 99%

Optimal Seeding Densities for In Vitro Chondrogenesis of Two- and Three-Dimensional-Isolated and -Expanded Bone Marrow-Derived Mesenchymal Stromal Stem Cells Within a Porous Collagen Scaffold

Bornes

Jomha

Mulet‐Sierra

et al. 2016

Tissue Engineering Part C: Methods

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Bone marrow-derived mesenchymal stromal stem cells (BMSCs) are a promising cell source for treating articular cartilage defects. The objective of this study was to assess the impact of cell seeding density within a collagen I scaffold on in vitro BMSC chondrogenesis following isolation and expansion in two-dimensional (2D) and three-dimensional (3D) environments. It was hypothesized that both expansion protocols would produce BMSCs capable of hyaline-like chondrogenesis with an optimal seeding density of 10 × 10 6 cells/cm 3 . Ovine BMSCs were isolated in a 2D environment by plastic adherence, expanded to passage two in flasks containing an expansion medium, and seeded within collagen I scaffolds at densities of 50, 10, 5, 1, and 0.5 × 10 6 BMSCs/cm 3 . For 3D isolation and expansion, aspirates containing known quantities of mononucleated cells (bone marrow-derived mononucleated cells [BMNCs]) were seeded on scaffolds at 50, 10, 5, 1, and 0.5 × 10 6 BMNCs/cm 3 and cultured in the expansion medium for an equivalent duration to 2D expansion. Constructs were differentiated in vitro in the chondrogenic medium for 21 days and assessed with reverse-transcription quantitative polymerase chain reaction, safranin O staining, histological scoring using the Bern Score, collagen immunofluorescence, and glycosaminoglycan (GAG) quantification. Two-dimensional-expanded BMSCs seeded at all densities were capable of proteoglycan production and displayed increased expressions of aggrecan and collagen II messenger RNA (mRNA) relative to pre-differentiation controls. Collagen II deposition was apparent in scaffolds seeded at 0.5-10 × 10 6 BMSCs/cm 3 . Chondrogenesis of 2D-expanded BMSCs was most pronounced in scaffolds seeded at 5-10 × 10 6 BMSCs/cm 3 based on aggrecan and collagen II mRNA, safranin O staining, Bern Score, total GAG, and GAG/deoxyribonucleic acid (DNA). For 3D-expanded BMSC-seeded scaffolds, increased aggrecan and collagen II mRNA expressions relative to controls were noted with all densities. Proteoglycan deposition was present in scaffolds seeded at 0.5-50 × 10 6 BMNCs/cm 3 , while collagen II deposition occurred in scaffolds seeded at 10-50 × 10 6 BMNCs/cm 3 . The

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“…27 Scaffolds that provide sufficient mechanical support at implantation reduce the need for extended culture periods before the repair surgery. The regenerated tissue would develop under physiological loading conditions, which may ideally provide better functional tissue.Another approach is to first precondition the cell-scaffold construct in vitro before implantation into the defect (e.g., [28][29][30][31][32] ). In vitro cultivation provides a controlled nutrient supply and loading environment that may be optimized for matrix synthesis to produce stiff cartilage-like constructs that may ideally sustain physiological loading following implantation.…”

mentioning

confidence: 99%

Toward Engineering a Biological Joint Replacement

2013

Articular Cartilage Injury of the Knee: Basic Science to Surgical Repair

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Osteoarthritis is a major cause of disability and pain for patients in the United States. Treatments for this degenerative disease represent a significant challenge considering the poor regenerative capacity of adult articular cartilage. Tissue-engineering techniques have advanced over the last two decades such that cartilage-like tissue can be cultivated in the laboratory for implantation. Even so, major challenges remain for creating fully functional tissue. This review article overviews some of these challenges, including overcoming limitations in nutrient supply to cartilage, improving in vitro collagen production, improving integration of engineered cartilage with native tissue, and exploring the potential for engineering full articular surface replacements. Keywordsbiological joint replacement; cartilage; tissue-engineering; nutrient diffusion; collagen production Over 20% of the adults in the United States (25 years and above) have osteoarthritis (OA) of the hip or knee (>46 million Americans). 1 OA is ranked as one of the top three causes for disability and contributes more than $185 billion dollars a year in related medical costs. [2][3][4] More than 580,000 arthroplasty procedures are performed each year in the U.S. 5 While joint replacement generally succeeds in decreasing or eliminating pain and restoring joint function, the lifespan of prostheses are limited due to wear, loosening, infection, and fracture of the implant or surrounding bone. 6-9 Alternative treatments have not yet been successful in providing a viable long-term option for cartilage repair. For example, allografts are limited by donor tissue availability and graft viability, 10,11 while autografts are limited by the availability of healthy tissue and donor site morbidity. Bio-engineered repair strategies that circumvent these limitations, while preserving the natural function of the joint and using Copyright © 2012 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript a procedure less invasive than total joint arthroplasty, may be optimal for treating younger OA patients.Articular cartilage serves as the load-bearing material of joints and possesses excellent friction, lubrication, and wear characteristics. 12 Successful replacement of damaged or injured articular cartilage will hinge on the ability to recapitulate the mechanical and structural properties of the healthy native tissue before implantation. Over the past two decades, there has been a wide interest in developing functional engineered cartilage. To grow cartilage tissue, cells are cultured within a three-dimensional (3D) scaffold that provides an initial structure for the de novo tissue [13][14][15] ; alternatively, cells may be cultured using scaffold-less techniques. 16,17 For example, autologous chondrocyte implantation (ACI) is a cell-based strategy where cells are injected directly into focal lesions and covered with a periosteal flap 18,19 whereas CARTIPATCH 18 uses a 3D agarose hydrogel scaffold to prevent leakage of cells, stabilize t...

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The restoration of full-thickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model

Cited by 39 publications

References 31 publications

Comparative, osteochondral defect repair: Stem cells versus chondrocytes versus Bone Morphogenetic Protein-2, solely or in combination

Comparative, osteochondral defect repair: Stem cells versus chondrocytes versus Bone Morphogenetic Protein-2, solely or in combination

Optimal Seeding Densities for In Vitro Chondrogenesis of Two- and Three-Dimensional-Isolated and -Expanded Bone Marrow-Derived Mesenchymal Stromal Stem Cells Within a Porous Collagen Scaffold

Toward Engineering a Biological Joint Replacement

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