Tensile properties of engineered cartilage formed from chondrocyte- and MSC-laden hydrogels

Huang, Alice H.; Yeger-McKeever, Meira; Stein, Ashley; Mauck, Robert L.

doi:10.1016/j.joca.2008.02.005

Cited by 104 publications

(119 citation statements)

References 50 publications

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“…In contrast, we found juvenile bovine MSCs are inferior in terms of functional ECM production to donormatched chondrocytes in various hydrogels [17,23,25,33] but have not considered MSC age in our hyaluronic acid (HA) hydrogel system. Thus, although the literature demonstrates aging affects MSC and chondrocyte function, the relative effects of aging of bovine chondrocytes compared with MSCs is unknown.…”

Section: Introductionmentioning

confidence: 87%

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Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

Erickson

Veen

Sengupta

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Cartilage degeneration is common in the aged, and aged chondrocytes are inferior to juvenile chondrocytes in producing cartilage-specific extracellular matrix. Mesenchymal stem cells (MSCs) are an alternative cell type that can differentiate toward the chondrocyte phenotype. Aging may influence MSC chondrogenesis but remains less well studied, particularly in the bovine system. Questions/purposes The objectives of this study were (1) to confirm age-related changes in bovine articular cartilage, establish how age affects chondrogenesis in cultured pellets for (2) chondrocytes and (3) MSCs, and (4) determine age-related changes in the biochemical and biomechanical development of clinically relevant MSC-seeded hydrogels. Methods Native bovine articular cartilage from fetal (n = 3 donors), juvenile (n = 3 donors), and adult (n = 3 donors) animals was analyzed for mechanical and biochemical properties (n = 3-5 per donor). Chondrocyte and MSC pellets (n = 3 donors per age) were cultured for 6 weeks before analysis of biochemical content (n = 3 per donor). Bone marrow-derived MSCs of each age were also cultured within hyaluronic acid hydrogels for 3 weeks and analyzed for matrix deposition and mechanical properties (n = 4 per age). Results Articular cartilage mechanical properties and collagen content increased with age. We observed robust matrix accumulation in three-dimensional pellet culture by fetal chondrocytes with diminished collagen-forming capacity in adult chondrocytes. Chondrogenic induction of MSCs was greater in fetal and juvenile cell pellets. Likewise, fetal and juvenile MSCs in hydrogels imparted greater matrix and mechanical properties. Conclusions Donor age and biochemical microenvironment were major determinants of both bovine chondrocyte and MSC functional capacity. Clinical Relevance In vitro model systems should be evaluated in the context of age-related changes and should be benchmarked against human MSC data.

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Section: Introductionmentioning

confidence: 87%

“…Cartilage, pellet, and hydrogel samples were papaindigested and assayed for DNA, GAG, and collagen content using the Picogreen (Molecular Probes, Eugene, OR), 1,9-dimethylmethylene blue [19], and orthohydroxyproline assays [38,45], respectively, as described in Erickson et al [17] and Huang et al [25].…”

Section: Methodsmentioning

confidence: 99%

Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

Erickson

Veen

Sengupta

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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“…From a functional standpoint, however, constructs created from gel-seeded ASCs or MSCs generally are unable to achieve the mechanical properties of native articular cartilage in a short period of culture time, particularly with respect to tension ( [4,40,71,78]). Thus there is an important need to develop scaffold materials that can provide biomechanical function for engineered constructs until the cells can synthesize and assemble a functional matrix [64].…”

Section: Functional Properties Of Tissue-engineered Cartilage Construmentioning

confidence: 99%

2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering

Guilak

Estes

Diekman

et al. 2010

Clinical Orthopaedics &Amp; Related Research

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Background Cell-based therapies such as tissue engineering provide promising therapeutic possibilities to enhance the repair or regeneration of damaged or diseased tissues but are dependent on the availability and controlled manipulation of appropriate cell sources. Questions/purposes The goal of this study was to test the hypothesis that adult subcutaneous fat contains stem cells with multilineage potential and to determine the influence of specific soluble mediators and biomaterial scaffolds on their differentiation into musculoskeletal phenotypes. Methods We reviewed recent studies showing the stemlike characteristics and multipotency of adipose-derived stem cells (ASCs), and their potential application in cellbased therapies in orthopaedics.

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“…32 MSCs were maintained in medium containing 10% fetal bovine serum and 1% penicillin= streptomycin=Fungizone (PSF), with cultures up to passage 3 used for these studies. Chondrocytes were harvested from carpometacarpal articular cartilage, 32 digested with pronase and collagenase, 21,41 and encapsulated immediately upon isolation.…”

Section: Msc and Chondrocyte Isolation And Culturementioning

confidence: 99%

“…30 A number of studies have examined the effects of varying cell seeding density on MSC chondrogenesis, although in most studies, the seeding densities employed were lower (<10 million cells=mL) than those used in cartilage tissue engineering with chondrocytes, and functional properties were not assayed. [31][32][33][34][35][36] Cell-cell contact and communication is a recognized factor in the initiation of chondrogenesis in pellet cultures, 37 although the effect of variation in this parameter has yet to be investigated in the context of emerging mechanical properties of MSC-seeded 3D constructs.…”

Section: Introductionmentioning

confidence: 99%

Transient Exposure to Transforming Growth Factor Beta 3 Improves the Mechanical Properties of Mesenchymal Stem Cell–Laden Cartilage Constructs in a Density-Dependent Manner

Huang

Stein

Tuan

et al. 2009

Tissue Engineering Part A

132

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Mesenchymal stem cells (MSCs) are an attractive cell source for cartilage tissue engineering and regenerative medicine. However, the use of these cells has been limited by their reduced ability to form functional tissue compared to chondrocytes when placed in three-dimensional culture systems. To optimize MSC functional chondrogenesis, we examined the effects of increasing seeding density and transient application of transforming growth factor beta 3 (TGF-b3), two factors previously shown to improve growth of chondrocyte-based constructs. Chondrocytes seeded in agarose at 20 million cells=mL and MSCs seeded at 20 or 60 million cells=mL agarose were cultured for 7 weeks under continuous or transient application of TGF-b3. In the transient group, cell-laden constructs were exposed to TGF-b3 for the initial 3 weeks, followed by 4 weeks of culture in medium without TGFb3. Compressive properties, biochemical content, and gene expression were assessed at 3, 5, and 7 weeks. Matrix distribution and collagen type was determined using histology and immunohistochemistry, and chondrogenic and osteogenic markers were assessed using real-time polymerase chain reaction. When maintained continuously with TGF-b3, chondrocyte-seeded constructs achieved a higher equilibrium compressive modulus than MSCs similarly maintained. Although properties of both groups increased with respect to starting values, there was no difference in bulk mechanical or biochemical properties with higher seeding density when MSCs were cultured with constant TGF-b3. Findings also showed that while transient application of TGF-b3 elicited robust growth from chondrocyte-laden gels, MSCs seeded at the same density failed to respond, although constructs maintained their previously accrued properties and continued to express cartilaginous genes after TGF-b3 removal. Conversely, MSCs seeded at 60 million cells=mL exhibited a strong anabolic response with transient TGF-b3 exposure, achieving an equilibrium modulus of approximately 200 kPa. Although this represents the highest modulus we have been able to achieve with MSC-seeded constructs using our culture system, further work remains to optimize MSC chondrogenesis for cartilage tissue engineering, particularly in terms of collagen content and dynamic mechanical properties.

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Tensile properties of engineered cartilage formed from chondrocyte- and MSC-laden hydrogels

Cited by 104 publications

References 50 publications

Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering

Transient Exposure to Transforming Growth Factor Beta 3 Improves the Mechanical Properties of Mesenchymal Stem Cell–Laden Cartilage Constructs in a Density-Dependent Manner

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