Primary chondrocytes enhance cartilage tissue formation upon co-culture with a range of cell types

Hendriks, Jan; Miclea, Razvan L.; Schotel, Roka; Bruijn, Ewart de; Moroni, Lorenzo; Karperien, Marcel; Riesle, Jens; Blitterswijk, Clemens A. van

doi:10.1039/c0sm00266f

Cited by 36 publications

(30 citation statements)

References 40 publications

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“…In the debate on the mechanisms behind the coculture-induced regeneration, there seems to have been a paradigm shift recently, based on evidence suggesting that MSCs, rather than differentiating, have trophic effects on chondrocytes (Fig. 1B) [46][47][48][49][50][51][52][53][54][55]. Nonetheless, regeneration may also result from both chondroinduction and MSC differentiation (Fig.…”

Section: Coculture-induced Tissue Regenerationmentioning

confidence: 99%

Concise Review: Unraveling Stem Cell Cocultures in Regenerative Medicine: Which Cell Interactions Steer Cartilage Regeneration and How?

Windt

Hendriks²,

Zhao

et al. 2014

Stem Cells Translational Medicine

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Section: Coculture-induced Tissue Regenerationmentioning

confidence: 99%

Concise Review: Unraveling Stem Cell Cocultures in Regenerative Medicine: Which Cell Interactions Steer Cartilage Regeneration and How?

Windt

Hendriks²,

Zhao

et al. 2014

Stem Cells Translational Medicine

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“…However, the beneficial effects of co-cultures for cartilage matrix formation was also found in a combination of chondrocytes and a variety of other cell types, such as adipose-tissue-derived stem cells, human embryonic stem cells, fibroblasts, and meniscus cells. [36][37][38][39] It is still unclear whether MSCs derived from adipose tissue or synovium have a comparable trophic role in the co-culture.…”

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

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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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“…However, with the cellular interactions between MSCs and native chondrocytes receiving less attention [9], the molecular mechanism of interactions between MSCs and native chondrocytes is poorly understood [10]. In order to maximize the benefits of stem cell therapy, these cellular interactions need to be clarified.Previous reports showed that cartilage matrix formation was increased in co-cultures of human primary chondrocytes (hPCs) with MSCs compared with monocultures [11,12]. Further investigations revealed that the inductive effects of MSCs on cartilage formation were predominantly due to stimulation of hPCs proliferation in the co-culture pellets [13].…”

mentioning

confidence: 99%

“…Previous reports showed that cartilage matrix formation was increased in co-cultures of human primary chondrocytes (hPCs) with MSCs compared with monocultures [11,12]. Further investigations revealed that the inductive effects of MSCs on cartilage formation were predominantly due to stimulation of hPCs proliferation in the co-culture pellets [13].…”

mentioning

confidence: 99%

Fibroblast Growth Factor-1 Is a Mesenchymal Stromal Cell-Secreted Factor Stimulating Proliferation of Osteoarthritic Chondrocytes in Co-Culture

Leijten

Blitterswijk

et al. 2013

Stem Cells and Development

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Previously, we showed that mesenchymal stromal cells (MSCs) in co-culture with primary chondrocytes secrete soluble factors that increase chondrocyte proliferation. The objective of this study is to identify these factors. Human primary chondrocytes (hPCs) isolated from late-stage osteoarthritis patients were co-cultured with human bone marrow-derived MSCs (hMSCs) in pellets. Genome-wide mRNA expression analysis and quantitative polymerase chain reactions (qPCR) were used to identify soluble factors that were specifically induced in co-cultures. Immunofluorescent staining combined with cell tracking and enzyme-linked immunosorbent assay (ELISA) were performed to validate up-regulation at the protein level and to identify the cellular origin of the increased proteins. Chemical blockers and neutralizing antibodies were used to elucidate the role of the identified candidate genes in co-cultures. A number of candidate factors were differentially regulated in co-cultures at the mRNA level. Of these, fibroblast growth factor-1 (FGF-1) mRNA and protein expression were markedly increased in co-cultures predominantly due to up-regulated expression in MSCs. Blocking of FGF signaling in co-culture pellets by specific FGF receptor inhibitors or FGF-1 neutralizing antibodies completely blocked hPCs proliferation. We demonstrate that MSCs increase FGF-1 secretion on co-culture with hPCs, which, in turn, is responsible for increased hPCs proliferation in pellet co-cultures. C artilage repair is among the key targets of regenerative medicine. Several stem cell-based therapies have been proposed to treat cartilage defects, rheumatic arthritis, osteoarthiris (OA), and other joint diseases. These therapeutic strategies include implantation or injection of mesenchymal stromal cells (MSCs) in the diseased joint or bone marrow stimulation techniques such as micro fracture. These procedures rely on cellular interactions between MSCs and native cells in the joint [1][2][3][4]. Recent studies showed that intra-articularly injected MSCs can reduce incidence and severity of arthritis in animal model by inducing immune tolerance [5]. Further investigations showed that MSCs are capable of inducing hyporesponsiveness of T-lymphocytes and of expressing antiinflammatory mediators in macrophages [6,7]. Besides immuno-suppressive effects, intra-articularly injected MSCs were also reported to inhibit thickening of the synovium and to protect against cartilage destruction in a mouse OA model [8]. However, with the cellular interactions between MSCs and native chondrocytes receiving less attention [9], the molecular mechanism of interactions between MSCs and native chondrocytes is poorly understood [10]. In order to maximize the benefits of stem cell therapy, these cellular interactions need to be clarified.Previous reports showed that cartilage matrix formation was increased in co-cultures of human primary chondrocytes (hPCs) with MSCs compared with monocultures [11,12]. Further investigations revealed that the inductive effects of MSCs on cartila...

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Primary chondrocytes enhance cartilage tissue formation upon co-culture with a range of cell types

Cited by 36 publications

References 40 publications

Concise Review: Unraveling Stem Cell Cocultures in Regenerative Medicine: Which Cell Interactions Steer Cartilage Regeneration and How?

Concise Review: Unraveling Stem Cell Cocultures in Regenerative Medicine: Which Cell Interactions Steer Cartilage Regeneration and How?

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

Fibroblast Growth Factor-1 Is a Mesenchymal Stromal Cell-Secreted Factor Stimulating Proliferation of Osteoarthritic Chondrocytes in Co-Culture

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