Chondrogenesis of mesenchymal stem cells in gel-like biomaterials in vitro and in vivo

Dickhut, Andrea; Gottwald, Eric; Steck, Eric; Heisel, Christian; Richter, Wiltrud

doi:10.2741/3020

Cited by 73 publications

(70 citation statements)

References 37 publications

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“…In agreement with what has been observed previously (Dickhut et al, 2008;Scotti et al, 2013;Sheehy et al, 2013;Vinardell et al, 2012), cartilage tissues engineered using BMSCs appeared to proceed down the endochondral pathway in vivo, with increased type X collagen expression and mineralisation of the engineered tissue. This occurred for both agarose encapsulation and SA.…”

Section: Discussionsupporting

confidence: 90%

“…While this is a major limitation associated with MSCs for articular cartilage tissue-engineering, this property has recently been leveraged for large bone defect regeneration (Harada et al, 2014;van der Stok et al, 2014). Previous studies have demonstrated that cartilaginous constructs engineered using BMSCs embedded in a hydrogel will proceed along an endochondral pathway in vivo (Dickhut et al, 2008;Vinardell et al, 2012). Indeed, previous work in our lab has shown that it is possible to engineer osteochondral constructs by spatially regulating endochondral ossification within bi-layered agarose cartilaginous grafts (Sheehy et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Tissue engineering scaled-up, anatomically shaped osteochondral constructs for joint resurfacing

Mesallati

Sheehy²,

Vinardell³

et al. 2015

eCM

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Arthroplasty is currently the only surgical procedure available to restore joint function following articular cartilage and bone degeneration associated with diseases such as osteoarthritis (OA). A potential alternative to this procedure would be to tissue-engineer a biological implant and use it to replace the entire diseased joint. The objective of this study was therefore to tissue-engineer a scaled-up, anatomically shaped, osteochondral construct suitable for partial or total resurfacing of a diseased joint. To this end it was first demonstrated that a bone marrow derived mesenchymal stem cell seeded alginate hydrogel could support endochondral bone formation in vivo within the osseous component of an osteochondral construct, and furthermore, that a phenotypically stable layer of articular cartilage could be engineered over this bony tissue using a co-culture of chondrocytes and mesenchymal stem cells. Co-culture was found to enhance the in vitro development of the chondral phase of the engineered graft and to dramatically reduce its mineralisation in vivo. In the final part of the study, tissue-engineered grafts (~ 2 cm diameter) mimicking the geometry of medial femorotibial joint prostheses were generated using laser scanning and rapid prototyped moulds. After 8 weeks in vivo, a layer of cartilage remained on the surface of these scaled-up engineered implants, with evidence of mineralisation and bone development in the underlying osseous region of the graft. These findings open up the possibility of a tissueengineered treatment option for diseases such as OA.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Tissue engineering scaled-up, anatomically shaped osteochondral constructs for joint resurfacing

Mesallati

Sheehy²,

Vinardell³

et al. 2015

eCM

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“…They can be derived from natural materials which are either components of, or have macro-molecular properties similar to, native extra-cellular matrix [17], and a number of naturally derived hydrogels have been shown to support chondrogenesis of MSCs in vitro [18][19][20][21][22]. Previous studies have compared the chondrogenic capabilities of MSC-seeded hydrogels in vitro [23][24][25][26], and also the potential of chondrogenically primed MSC-seeded hydrogels to maintain a stable chondrogenic phenotype in vivo [27][28][29]. However, little is known about the capacity of different MSCseeded hydrogels to support the development of either phenotypically stable cartilage or endochondral bone in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

et al. 2015

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Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) have been shown to generate bone in vivo by executing an endochondral program. This may hinder the use of MSCs for articular cartilage regeneration, but opens the possibility of using engineered cartilaginous tissues for large bone defect repair. Hydrogels may be an attractive tool in the scaling-up of such tissue engineered grafts for endochondral bone regeneration. In this study, we compared the capacity of different naturally derived hydrogels (alginate, chitosan, and fibrin) to support chondrogenesis and hypertrophy of MSCs in vitro and endochondral ossification in vivo. In vitro, alginate and chitosan constructs accumulated the highest levels of sGAG, with chitosan constructs synthesising the highest levels of collagen. Alginate and fibrin constructs supported the greatest degree of calcium accumulation, though only fibrin constructs calcified homogenously. In vivo, chitosan constructs facilitated neither vascularization nor endochondral ossification, and also retained the greatest amount of sGAG, suggesting it to be a more suitable material for the engineering of articular cartilage.Both alginate and fibrin constructs facilitated vascularization and endochondral bone formation as well as the development of a bone marrow environment. Alginate constructs accumulated significantly more mineral and supported greater bone formation in central regions of the engineered tissue. In conclusion, this study demonstrates the capacity of chitosan hydrogels to promote and better maintain a chondrogenic phenotype in MSCs and highlights the potential of utilizing alginate hydrogels for MSC-based endochondral bone tissue engineering applications.

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“…There is also evidence to suggest that joint tissue derived multipotent stromal cells, such as those isolated from the infrapatellar fat pad (IFP) or synovium, may possess a superior chondrogenic potential to those derived from alternative sources (Sakaguchi et al, 2005;Vinardell et al, 2012b). In spite of this, the in vivo phenotypic stability of cartilaginous tissues engineered using such cells, irrespective of their origin, is by no means assured (De Bari et al, 2004;Pelttari et al, 2006;Hennig et al, 2007;Dickhut et al, 2008). Previous studies have shown that following in vivo subcutaneous implantation, IFP derived multipotent stromal cells (FPSCs) tend to undergo fibrous dedifferentiation or resorption, as evidenced by increased collagen type I and reduced sulphated glycosaminoglycan (sGAG) content, whereas bone marrow derived multipotent stromal cells (BMSCs) tend to follow an endochondral pathway, with increased mineralisation and vascularisation of the engineered tissue (Pelttari et al, 2006;Vinardell et al, 2012b).…”

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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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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Chondrogenesis of mesenchymal stem cells in gel-like biomaterials in vitro and in vivo

Cited by 73 publications

References 37 publications

Tissue engineering scaled-up, anatomically shaped osteochondral constructs for joint resurfacing

Tissue engineering scaled-up, anatomically shaped osteochondral constructs for joint resurfacing

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

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

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