Structured three-dimensional co-culture of mesenchymal stem cells with chondrocytes promotes chondrogenic differentiation without hypertrophy

Cooke, Margaret E.; Allon, Aliza A.; Cheng, Thomas K.; Kuo, Alfred C.; Kim, H.T.; Vail, Thomas P.; Marcucio, Ralph; Schneider, Richard A.; Lotz, Jeffrey C.; Alliston, Tamara

doi:10.1016/j.joca.2011.07.005

Cited by 110 publications

(110 citation statements)

References 39 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…In vitro a structured bi-layered co-culture enhanced Previous studies have demonstrated that in vitro hypertrophy of MSCs is inhibited through co-culture with chondrocytes [50][51], with parathyroid hormone-related protein secreted by chondrocytes proposed as one mechanism by which this suppression of terminal differentiation occurs [52]. In the present study a structured bi-layered chondrogenic coculture differentially regulated the synthesis of collagen by chondrocytes and MSCs within the construct.…”

Section: Discussionmentioning

confidence: 52%

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

Section: Discussionmentioning

confidence: 52%

Engineering osteochondral constructs through spatial regulation of endochondral ossification

et al. 2013

View full text Add to dashboard Cite

show abstract

“…As we know, chondrogenic cells commonly begin hypertrophic differentiation after 21 d [28][29][30][31], and we also showed that the hypertrophic marker Col10a1 was significantly increased after 21 d of chondrogenic differentiation; thus, miR-455-3p might be involved in the acceleration of early chondrogenesis, but not hypertrophic differentiation.…”

Section: Discussionmentioning

confidence: 67%

MiR‐455‐3p regulates early chondrogenic differentiation via inhibiting Runx2

et al. 2015

View full text Add to dashboard Cite

Edited by Zhijie ChangKeywords: Chondrogenesis MiR-455-3p Runt-related transcription factor 2 a b s t r a c tThe expression of miR-455-3p has been shown to be up-regulated in chondrogenesis of mesenchymal stem cell, but its role in different stages during chondrogenesis remains unknown. Here, we show that miR-455-3p is increased in ATDC5 cells from 0 d to 21 d, but rapidly decreases at 28 d, and a similar expression kinetic is detected in the development of mouse embryos. We show that miR-455-3p functions as an activator for early chondrogenic differentiation, most likely by inhibiting the expression of Runt-related transcription factor 2 (Runx2) as indicated by luciferase reporter assays. In conclusion, miR-455-3p may activate early chondrogenesis by directly targeting Runx2.

show abstract

“…MSCs are multipotent stem cells primarily isolated from bone marrow. These cells differentiate into several cell lineages including osteogenic and chondrogenic [8,9]. More recently described induced pluripotent stem cells (iPSCs) have the potential to differentiate into somatic cells, including chondrocytes [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Induced Pluripotent and Mesenchymal Stem Cells as a Promising Tool for Articular Cartilage Regeneration

Trzeciak¹,

Augustyniak²,

Richter³

et al. 2014

J Cell Sci Ther

View full text Add to dashboard Cite

The application of stem cells in regenerative medicine has recently become a rapidly growing field, holding promise for combating a number of orthopedic disorders including osteodegenerative ones (osteoporosis and osteoarthritis). Although the differentiation of stem cells into chondrocytes is now intensively investigated on a laboratory scale, implementing the laboratory protocols in clinical practice requires a scale-up culture. In order to apply this technique many aspects of stem cell bioprocessing such as optimal culture conditions for anchoragedependent or anchorage-independent cells and the type of culture must be taken into account. The presence of microcarriers and/or scaffolds for adherent cells is essential, since they provide a three-dimensional microenvironment indispensable for cell growth. For treatment of osteoarthritis, induced pluripotent stem cells and mesenchymal stem cells seem to be the best choice. Although, the scale-up culture using stem cells has been intensively investigated on a laboratory scale, the scale-up culture for clinical application still requires further technical improvements.In this review stem cell bioprocessing including the use of biomaterials, bioreactors, and factors affecting this process, as well as scale-up culture of induced Pluripotent and mesenchymal stem cells were presented and discussed.

show abstract

Structured three-dimensional co-culture of mesenchymal stem cells with chondrocytes promotes chondrogenic differentiation without hypertrophy

Cited by 110 publications

References 39 publications

Engineering osteochondral constructs through spatial regulation of endochondral ossification

Engineering osteochondral constructs through spatial regulation of endochondral ossification

MiR‐455‐3p regulates early chondrogenic differentiation via inhibiting Runx2

Induced Pluripotent and Mesenchymal Stem Cells as a Promising Tool for Articular Cartilage Regeneration

Contact Info

Product

Resources

About