State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products

Hildner, Florian; Albrecht, Christian; Gabriel, Christian; Redl, Heinz; Griensven, Martijn van

doi:10.1002/term.386

Cited by 82 publications

(76 citation statements)

References 182 publications

(209 reference statements)

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“…15,30 Piles of documents had pointed out the potential use of AT-MSCs in a variety of tissue-engineering applications. [40][41][42][43] Although less studies have been performed with synovium-derived MSCs, the synovium has recently received attention as a promising cell source for cartilage tissue engineering. 24,31,44 Here, we report for the first time that MSCs isolated from bone marrow, adipose tissue, and synovium behave similarly in coculture pellets with MSCs by acting as trophic mediators stimulating chondrocyte proliferation and matrix production.…”

Section: Figmentioning

confidence: 99%

Trophic Effects of Mesenchymal Stem Cells in Chondrocyte Co-Cultures are Independent of Culture Conditions and Cell Sources

Prins

Helder

et al. 2012

Tissue Engineering Part A

192

173

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Earlier, we have shown that the increased cartilage production in pellet co-cultures of chondrocytes and bone marrow-derived mesenchymal stem cells (BM-MSCs) is due to a trophic role of the MSC in stimulating chondrocyte proliferation and matrix production rather than MSCs actively undergoing chondrogenic differentiation. These studies were performed in a culture medium that was not compatible with the chondrogenic differentiation of MSCs. In this study, we tested whether the trophic role of the MSCs is dependent on culturing co-culture pellets in a medium that is compatible with the chondrogenic differentiation of MSCs. In addition, we investigated whether the trophic role of the MSCs is dependent on their origins or is a more general characteristic of MSCs. Human BM-MSCs and bovine primary chondrocytes were co-cultured in a medium that was compatible with the chondrogenic differentiation of MSCs. Enhanced matrix production was confirmed by glycosaminoglycans (GAG) quantification. A species-specific quantitative polymerase chain reaction demonstrated that the cartilage matrix was mainly of bovine origin, indicative of a lack of the chondrogenic differentiation of MSCs. In addition, pellet co-cultures were overgrown by bovine cells over time. To test the influence of origin on MSCs' trophic effects, the MSCs isolated from adipose tissue and the synovial membrane were co-cultured with human primary chondrocytes, and their activity was compared with BM-MSCs, which served as control. GAG quantification again confirmed increased cartilage matrix production, irrespective of the source of the MSCs. EdU staining combined with cell tracking revealed an increased proliferation of chondrocytes in each condition. Irrespective of the MSC source, a short tandem repeat analysis of genomic DNA showed a decrease in MSCs in the co-culture over time. Our results clearly demonstrate that in co-culture pellets, the MSCs stimulate cartilage formation due to a trophic effect on the chondrocytes rather than differentiating into chondrocytes, irrespective of culture condition or origin. This implies that the trophic effect of MSCs in co-cultures is a general phenomenon with potential implications for use in cartilage repair strategies. Introduction Despite the success of autologous chondrocyte implantation in treating large-size cartilage defects, there are some disadvantages of this treatment that limit its broader clinical application. One major issue is the requirement of relatively large quantities of chondrocytes from the patient, 1 which are obtained by in vitro expansion. The partial replacement of the chondrocytes with mesenchymal stem cells (MSC) has been proposed to tackle this problem. Many studies have evaluated the feasibility of this idea by the coculturing of MSCs and chondrocytes.2 Indeed, cartilage matrix deposition was found to be improved in the cocultures of MSCs and chondrocytes compared with the cultures of pure chondrocytes or MSCs. 3,4 In our previous report, 5 we have shown that pellet co-cultures of bovine pri...

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Section: Figmentioning

confidence: 99%

Trophic Effects of Mesenchymal Stem Cells in Chondrocyte Co-Cultures are Independent of Culture Conditions and Cell Sources

Prins

Helder

et al. 2012

Tissue Engineering Part A

192

173

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“…The variety of treatment options available implies that there is no single, ideal, reliable and predictable therapy (Hildner et al, 2011). The use of mesenchymal stem cells (MSCs) as part of a cell based therapy for cartilage repair is very appealing.…”

Section: Introductionmentioning

confidence: 99%

Hydrostatic pressure acts to stabilise a chondrogenic phenotype in porcine joint tissue derived stem cells

Vinardell

Rolfe²,

Buckley³

et al. 2012

eCM

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Hydrostatic pressure (HP) is a key component of the in vivo joint environment and has been shown to enhance chondrogenesis of stem cells. The objective of this study was to investigate the interaction between HP and TGF-β3 on both the initiation and maintenance of a chondrogenic phenotype for joint tissue derived stem cells. Pellets generated from porcine chondrocytes (CCs), synovial membrane derived stem cells (SDSCs) and infrapatellar fat pad derived stem cells (FPSCs) were subjected to 10 MPa of cyclic HP (4 h/day) and different concentrations of TGF-β3 (0, 1 and 10 ng/mL) for 14 days. CCs and stem cells were observed to respond differentially to both HP and TGF-β3 stimulation. HP in the absence of TGF-β3 did not induce robust chondrogenic differentiation of stem cells. At low concentrations of TGF-β3 (1 ng/mL), HP acted to enhance chondrogenesis of both SDSCs and FPSCs, as evident by a 3-fold increase in Sox9 expression and a signifi cant increase in glycosaminoglycan accumulation. In contrast, HP had no effect on cartilage-specifi c matrix synthesis at higher concentrations of TGF-β3 (10 ng/mL).Critically, HP appears to play a key role in the maintenance of a chondrogenic phenotype, as evident by a downregulation of the hypertrophic markers type X collagen and Indian hedgehog in SDSCs irrespective of the cytokine concentration. In the context of stem cell based therapies for cartilage repair, this study demonstrates the importance of considering how joint specifi c environmental factors interact to regulate not only the initiation of chondrogenesis, but also the development of a stable hyaline-like repair tissue.

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“…This is paradoxical to the fact that clinical cases often occur in aged individuals (Wilson et al, 2010;Kasper et al, 2009). Adult cells with chondrogenic potential have been isolated from a large number of tissues and have been reviewed elsewhere (Solchaga et al, 2011;Hildner et al, 2011;O'Sullivan et al, 2011). Embryonic and recently, induced pluripotent stem cells (iPS cells), may also be valuable cell sources for cartilage repair (Hiramatsu et al, 2011;Medvedev et al, 2010;Waese and Stanford, 2011;Fecek et al, 2008).…”

Section: Cells Of Cartilage Tissue Engineeringmentioning

confidence: 99%

Joint Cartilage Tissue Engineering and Pre-Clinical Safety and Efficacy Testing

Koch¹,

Moroni²,

Leysi-Derilou³

et al. 2011

Tissue Engineering for Tissue and Organ Regeneration

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State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products

Cited by 82 publications

References 182 publications

Trophic Effects of Mesenchymal Stem Cells in Chondrocyte Co-Cultures are Independent of Culture Conditions and Cell Sources

Trophic Effects of Mesenchymal Stem Cells in Chondrocyte Co-Cultures are Independent of Culture Conditions and Cell Sources

Hydrostatic pressure acts to stabilise a chondrogenic phenotype in porcine joint tissue derived stem cells

Joint Cartilage Tissue Engineering and Pre-Clinical Safety and Efficacy Testing

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