Cell–matrix interactions regulate mesenchymal stem cell response to hydrostatic pressure

Steward, Andrew J.; Thorpe, Stephen D.; Vinardell, Tatiana; Buckley, Conor T.; Wagner, Diane R.; Kelly, Daniel J.

doi:10.1016/j.actbio.2012.03.016

Cited by 79 publications

(65 citation statements)

References 40 publications

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“…Articular cartilage is a multiphasic tissue, the solid phase of which is composed predominately of a collagen (mainly type II) fibrillar network (around 10-22% by wet weight) enmeshing proteoglycan macromolecules (2-7% by wet weight) (Maroudas et al, 1969;Muir et al, 1970;Bayliss and Ali, 1978;Inerot et al, 1978;Maroudas et al, 1980;Zirn et al, 1984;Mow et al, 1992;Rieppo et al, 2009;Gannon et al, 2012). Previous studies have demonstrated that the application of dynamic compression (Huang et al, 2010;Bian et al, 2012;Thorpe et al, 2013) or hydrostatic pressure (Miyanishi et al, 2006;Wagner et al, 2008;Ogawa et al, 2009;Huang et al, 2010;Meyer et al, 2011;Correia et al, 2012;Liu et al, 2012;Steward et al, 2012;Vinardell et al, 2012a;Liu et al, 2013) can enhance the sGAG and collagen content as well as the mechanical functionality of cartilage constructs engineered using MSCs. However, these studies often fail to produce cartilage grafts with mechanical functionality or ECM content approaching that of native cartilage.…”

Section: Discussionmentioning

confidence: 99%

“…Mechanical signals, such as hydrostatic pressure (HP), are a key component of the in vivo joint environment and have been shown to play a significant role in regulating the chondrogenic differentiation of mesenchymal stem cells. Previous studies have shown varying and occasionally conflicting results (Parkkinen et al, 1993;Carver and Heath, 1999;Suh et al, 1999;Carver and Heath, 2000;Jortikka et al, 2000;Smith et al, 2000Smith et al, , 2005Hu and Athanasiou, 2006;Finger et al, 2007;Ogawa et al, 2009;Meyer et al, 2011;Liu et al, 2012;Maxson and Burg, 2012;Puetzer et al, 2012;Safshekan et al, 2012;Steward et al, 2012;Vinardell et al, 2012a;Steward et al, 2013), but it would appear that the application of physiological levels (3-10 MPa) of intermittent HP can enhance proteoglygan and collagen synthesis and upregulate aggrecan and collagen II mRNA expression in chondrocytes and stem/progenitor cells isolated from bone marrow, synovial tissues and adipose tissues. There is also evidence to suggest that dynamic HP can act to stabilise the phenotype of chondrogenically primed joint tissue derived MSCs (Vinardell et al, 2012a).…”

Section: Introductionmentioning

confidence: 99%

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Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad

Carroll

Buckley

Kelly

2014

Journal of Biomechanics

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a b s t r a c tThe objective of this study was to investigate how joint specific biomechanical loading influences the functional development and phenotypic stability of cartilage grafts engineered in vitro using stem/progenitor cells isolated from different source tissues. Porcine bone marrow derived multipotent stromal cells (BMSCs) and infrapatellar fat pad derived multipotent stromal cells (FPSCs) were seeded in agarose hydrogels and cultured in chondrogenic medium, while simultaneously subjected to 10 MPa of cyclic hydrostatic pressure (HP). To mimic the endochondral phenotype observed in vivo with cartilaginous tissues engineered using BMSCs, the culture media was additionally supplemented with hypertrophic factors, while the loss of phenotype observed in vivo with FPSCs was induced by withdrawing transforming growth factor (TGF)-β3 from the media. The application of HP was found to enhance the functional development of cartilaginous tissues engineered using both BMSCs and FPSCs. In addition, HP was found to suppress calcification of tissues engineered using BMSCs cultured in chondrogenic conditions and acted to maintain a chondrogenic phenotype in cartilaginous grafts engineered using FPSCs. The results of this study point to the importance of in vivo specific mechanical cues for determining the terminal phenotype of chondrogenically primed multipotent stromal cells. Furthermore, demonstrating that stem or progenitor cells will appropriately differentiate in response to such biophysical cues might also be considered as an additional functional assay for evaluating their therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad

Carroll

Buckley

Kelly

2014

Journal of Biomechanics

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“…The subcutaneous environment differs in a number of notable ways to the orthotopic environment. Mechanical cues, absent in the subcutaneous environment, such as hydrostatic pressure [59][60] and dynamic compression [61][62] have been shown to play a role in regulating the endochondral phenotype of MSCs as well as matrix production [63].…”

Section: Discussionmentioning

confidence: 99%

Engineering osteochondral constructs through spatial regulation of endochondral ossification

et al. 2013

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Chondrogenically primed bone marrow derived mesenchymal stem cells (MSCs) have been shown to become hypertrophic and undergo endochondral ossification when implanted in vivo. Modulating this endochondral phenotype may be an attractive approach to engineering the osseous phase of an osteochondral implant. The objective of this study was to engineer an osteochondral tissue by promoting endochondral ossification in one layer of a bi-layered construct and stable cartilage in the other. The top-half of bi-layered agarose hydrogels were seeded with culture expanded chondrocytes (termed chondral layer) and the bottom half of the bi-layered agarose hydrogels with MSCs (termed osseous layer). Constructs were cultured in a chondrogenic medium for 21 days and thereafter were either maintained in a chondrogenic medium, transferred to a hypertrophic medium, or implanted subcutaneously into nude mice. This structured chondrogenic bi-layered co-culture was found to enhance chondrogenesis in the chondral layer, appearing to help re-establish the chondrogenic phenotype that is lost in chondrocytes during monolayer expansion. Furthermore, the bilayered co-culture appeared to suppress hypertrophy and mineralisation in the osseous layer.The addition of hypertrophic factors to the media was found to induce mineralisation of the osseous layer in vitro. A similar result was observed in vivo where endochondral ossification was restricted to the osseous layer of the construct leading to the development of an osteochondral tissue. This novel approach represents a potential new treatment strategy for the repair of osteochondral defects.

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“…Multiple soluble and insoluble cues are known to regulate the differentiation of mesenchymal stem cells (MSCs), although we are only beginning to understand how these factors interact to regulate cell fate Engler et al, 2006;Kelly and Jacobs, 2010;McBeath et al, 2004;Steward et al, 2011;Thorpe et al, 2012). The matrix or substrate stiffness has been shown to play a role in regulating the differentiation of MSCs down specific lineages in both 2D (Engler et al, 2006;Park et al, 2011) and 3D environments (Huebsch et al, 2010;Parekh et al, 2011;Pek et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

The pericellular environment regulates cytoskeletal development and the differentiation of mesenchymal stem cells and determines their response to hydrostatic pressure

Steward

Wagner²,

Kelly³

2013

eCM

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The objective of this study was to examine the interplay between matrix stiffness and hydrostatic pressure (HP) in regulating chondrogenesis of mesenchymal stem cells (MSCs) and to further elucidate the mechanotransductive roles of integrins and the cytoskeleton. MSCs were seeded into 1 %, 2 % or 4 % agarose hydrogels and exposed to cyclic hydrostatic pressure. In a permissive media, the stiffer hydrogels supported an osteogenic phenotype, with little evidence of chondrogenesis observed regardless of the matrix stiffness. In a chondrogenic media, the stiffer gels suppressed cartilage matrix production and gene expression, with the addition of RGDS (an integrin blocker) found to return matrix synthesis to similar levels as in the softer gels. Vinculin, actin and vimentin organisation all adapted within stiffer hydrogels, with the addition of RGDS again preventing these changes. While the stiffer gels inhibited chondrogenesis, they enhanced mechanotransduction of HP. RGDS suppressed the mechanotransduction of HP, suggesting a role for integrin binding as a regulator of both matrix stiffness and HP. Intermediate filaments also appear to play a role in the mechanotransduction of HP, as only vimentin organisation adapted in response to this mechanical stimulus. To conclude, the results of this study demonstrate that matrix density and/or stiffness modulates the development of the pericellular matrix and consequently integrin binding and cytoskeletal structure. The study further suggests that physiological cues such as HP enhance chondrogenesis of MSCs as the pericellular environment matures and the cytoskeleton adapts, and points to a novel role for vimentin in the transduction of HP.

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Cell–matrix interactions regulate mesenchymal stem cell response to hydrostatic pressure

Cited by 79 publications

References 40 publications

Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad

Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad

Engineering osteochondral constructs through spatial regulation of endochondral ossification

The pericellular environment regulates cytoskeletal development and the differentiation of mesenchymal stem cells and determines their response to hydrostatic pressure

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