In vitro chondrogenic differentiation of human mesenchymal stem cells in collagen microspheres: Influence of cell seeding density and collagen concentration

Hui, T.Y.; Cheung, Kenneth M.C.; Cheung, WH; Chan, Danny; Chan, Barbara Pui

doi:10.1016/j.biomaterials.2008.04.001

Cited by 185 publications

(154 citation statements)

References 60 publications

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“…21,39 Contrary to our original hypothesis, MSCs seeded in agarose at 20 and 60 million cells=mL and maintained continuously with TGF-b3 showed no differences in functional properties or biochemical content after 7 weeks in freeswelling culture. Although several studies have reported enhanced chondrogenesis with greater seeding density, 31,33,35,36 the range of cell densities assayed were generally less than 10 million cells=mL, 33,35 and outcome parameters were limited to biochemical measures or gene expression. In one study comparing seeding densities greater than 10 million cells=mL, total GAG deposition was indistinguishable between constructs seeded at 12 to 48 million cells=mL, consistent with the current findings.…”

Section: Discussionmentioning

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%

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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

133

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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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Section: Discussionmentioning

confidence: 99%

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

133

View full text Add to dashboard Cite

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“…Therefore, cell adhesion was the vital step for MSCs chondrogenic differentiation. However, cell density strongly influences MSCs differentiation and cell-matrix secretion (Hui et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Cartilage Tissue Engineering Using Mesenchymal Stem Cells and 3D Chitosan Scaffolds – In vitro and in vivo Assays

Breyner¹,

Zonari²,

Carvalho³

et al. 2011

Biomaterials Science and Engineering

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“…In one reported approach to address this issue, a collagen/mesenchymal stem cell (MSC) suspension was fabricated into microspheres, where the cell-induced contraction improved mechanical stability [81]. The MSCs were also shown to retain viability and multipotency to differentiate down both chondrogenic [82] and osteogenic [83] lineages.…”

Section: Injectable Microspheres For Tissue Engineeringmentioning

confidence: 99%

Nanostructured Injectable Cell Microcarriers for Tissue Regeneration

Zhang

Eyster

Peter

2016

Nanomedicine (Lond.)

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Biodegradable polymer microspheres have emerged as cell carriers for the regeneration and repair of irregularly shaped tissue defects due to their injectability, controllable biodegradability and capacity for drug incorporation and release. Notably, recent advances in nanotechnology allowed the manipulation of the physical and chemical properties of the microspheres at the nanoscale, creating nanostructured microspheres mimicking the composition and/or structure of natural extracellular matrix. These nanostructured microspheres, including nanocomposite microspheres and nanofibrous microspheres, have been employed as cell carriers for tissue regeneration. They enhance cell attachment and proliferation, promote positive cell-carrier interactions and facilitate stem cell differentiation for target tissue regeneration. This review highlights the recent advances in nanostructured microspheres that are employed as injectable, biomimetic and cell-instructive cell carriers.

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In vitro chondrogenic differentiation of human mesenchymal stem cells in collagen microspheres: Influence of cell seeding density and collagen concentration

Cited by 185 publications

References 60 publications

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

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

Cartilage Tissue Engineering Using Mesenchymal Stem Cells and 3D Chitosan Scaffolds – In vitro and in vivo Assays

Nanostructured Injectable Cell Microcarriers for Tissue Regeneration

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