The effect of cyclic hydrostatic pressure on the functional development of cartilaginous tissues engineered using bone marrow derived mesenchymal stem cells

Meyer, Eric G.; Buckley, Conor T.; Steward, Andrew J.; Kelly, Daniel J.

doi:10.1016/j.jmbbm.2011.04.012

Cited by 70 publications

(60 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous research has shown that vimentin can directly interact with actin, integrins αvβ3 and α2β1, and their associated focal adhesions, which, together with the results of the current study, provides a mechanism by which vimentin may play a role in the transduction of mechanical cues (Esue et al, 2006;Gonzales et al, 2001;Kreis et al, 2005;Ruoslahti, 1996). The results of these and the present study demonstrate that although vimentin is critical for chondrogenesis, adaption of the intermediate filament Prior studies have demonstrated that the application of HP can enhance chondrogenesis of MSCs (Elder and Athanasiou, 2009) and improve the mechanical functionality of tissue engineered cartilage Meyer et al, 2011). Previously, we observed that the application of HP enhances chondrogenesis of MSCs in fibrin hydrogels where cells adopt a spread morphology with clear stress fibre formation, while MSCs embedded in agarose hydrogels remained rounded and did not respond to loading.…”

Section: Aj Steward Et Al Pericellular Environment and Msc Chondrogesupporting

confidence: 60%

“…Specifically, hydrostatic pressure (HP) is a key regulator AJ Steward et al Pericellular environment and MSC chondrogenesis of chondrogenesis (Elder and Athanasiou, 2009). HP has been shown to increase chondrogenic gene expression and matrix production in MSCs (Angele et al, 2003;Luo and Seedhom, 2007;Meyer et al, 2011;Miyanishi et al, 2006a;Miyanishi et al, 2006b;Ogawa et al, 2009;Wagner et al, 2008). HP also plays a role in maintaining the chondrogenic phenotype by suppressing the expression of type I collagen, alkaline phosphatase (ALP), matrix metalloproteinase 13 (MMP-13), type X collagen and Indian hedgehog (Ihh) Vinardell et al, 2012;Wong et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: Aj Steward Et Al Pericellular Environment and Msc Chondrogesupporting

confidence: 60%

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

View full text Add to dashboard Cite

show abstract

“…Another limitation of this study is the use of ascorbic acid and dexamethasone in the chondrogenic medium, which might be expected to cause MSCs to differentiate toward the osteogenic lineage. However, the use of dexamethasone and ascorbic acid in the chondrogenic medium is well documented 53,60,66,78,[91][92][93][94][95][96][97][98][99][100][101][102] and has not been shown to cause mineralization. Moreover, alizarin red staining of the aggregates before the coculture showed no positive staining and the control groups were all exposed to the same chondrogenic medium, so any differences seen between the groups were not because of exposure to these growth factors.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

View full text Add to dashboard Cite

In vitro bone regeneration strategies that prime mesenchymal stem cells (MSCs) with chondrogenic factors, to mimic aspects of the endochondral ossification process, have been shown to promote mineralization and vascularization by MSCs both in vitro and when implanted in vivo. However, these approaches required the use of osteogenic supplements, namely dexamethasone, ascorbic acid, and b-glycerophosphate, none of which are endogenous mediators of bone formation in vivo. Rather MSCs, endothelial progenitor cells, and chondrocytes all reside in proximity within the cartilage template and might paracrineally regulate osteogenic differentiation. Thus, this study tests the hypothesis that an in vitro bone regeneration approach that mimics the cellular niche existing during endochondral ossification, through coculture of MSCs, endothelial cells, and chondrocytes, will obviate the need for extraneous osteogenic supplements and provide an alternative strategy to elicit osteogenic differentiation of MSCs and mineral production. The specific objectives of this study were to (1) mimic the cellular niche existing during endochondral ossification and (2) investigate whether osteogenic differentiation could be induced without the use of any external growth factors. To test the hypothesis, we evaluated the mineralization and vessel formation potential of (a) a novel methodology involving both chondrogenic priming and the coculture of human umbilical vein endothelial cells (HUVECs) and MSCs compared with (b) chondrogenic priming of MSCs alone, (c) addition of HUVECs to chondrogenically primed MSC aggregates, (d-f) the same experimental groups cultured in the presence of osteogenic supplements and (g) a noncoculture group cultured in the presence of osteogenic growth factors alone. Biochemical (DNA, alkaline phosphatase [ALP], calcium, CD31 + , vascular endothelial growth factor [VEGF]), histological (alcian blue, alizarin red), and immunohistological (CD31 + ) analyses were conducted to investigate osteogenic differentiation and vascularization at various time points (1, 2, and 3 weeks). The coculture methodology enhanced both osteogenesis and vasculogenesis compared with osteogenic differentiation alone, whereas osteogenic supplements inhibited the osteogenesis and vascularization (ALP, calcium, and VEGF) induced through coculture alone. Taken together, these results suggest that chondrogenic and vascular priming can obviate the need for osteogenic supplements to induce osteogenesis of human MSCs in vitro, while allowing for the formation of rudimentary vessels.

show abstract

“…Well documented limitations associated with chondrocytes [28][29] have led to increased interest in the use of mesenchymal stem cells (MSCs) for functional cartilage tissue engineering strategies [30][31][32][33][34][35][36][37]. A major challenge in MSC based cartilage repair therapies is the prevention of terminal differentiation as maintenance of the chondrogenic phenotype is critical in order to ensure the long-term in vivo stability of a cartilaginous graft [38].…”

Section: Introductionmentioning

confidence: 99%

Engineering osteochondral constructs through spatial regulation of endochondral ossification

et al. 2013

View full text Add to dashboard Cite

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.

show abstract

The effect of cyclic hydrostatic pressure on the functional development of cartilaginous tissues engineered using bone marrow derived mesenchymal stem cells

Cited by 70 publications

References 45 publications

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

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

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Engineering osteochondral constructs through spatial regulation of endochondral ossification

Contact Info

Product

Resources

About