Plasticity of clonal populations of dedifferentiated adult human articular chondrocytes

Barbero, Andrea; Ploegert, Sabine; Heberer, Michael; Martin, Ivan

doi:10.1002/art.10950

Cited by 344 publications

(343 citation statements)

References 42 publications

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“…22 Additional supplementation of TGF-b1 and PDGFbb to the culture medium during expansion did not further increase goat chondrocyte growth or GAG content in pellets, in contrast to recent findings with human chondrocytes. 13,29 These results indicate that mammalian chondrocytes share common paradigms of response to growth factors, but with species-related specificity, 30,31 thus highlighting the limit of using animal models for growth factor-based cartilage repair approaches.…”

Section: Discussionmentioning

confidence: 93%

Cartilage tissue engineering by expanded goat articular chondrocytes

Miot

Freitas

Wirz

et al. 2006

Journal Orthopaedic Research

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In this study we investigated whether expanded goat chondrocytes have the capacity to generate cartilaginous tissues with biochemical and biomechanical properties improving with time in culture. Goat chondrocytes were expanded in monolayer with or without combinations of FGF-2, TGF-b1, and PDGFbb, and the postexpansion chondrogenic capacity assessed in pellet cultures. Expanded chondrocytes were also cultured for up to 6 weeks in HYAFF 1 -M nonwoven meshes or Polyactive TM foams, and the resulting cartilaginous tissues were assessed histologically, biochemically, and biomechanically. Supplementation of the expansion medium with FGF-2 increased the proliferation rate of goat chondrocytes and enhanced their postexpansion chondrogenic capacity. FGF-2-expanded chondrocytes seeded in HYAFF 1 -M or Polyactive TM scaffolds formed cartilaginous tissues with wet weight, glycosaminoglycan, and collagen content, increasing from 2 days to 6 weeks culture (up to respectively 2-, 8-, and 41-fold). Equilibrium and dynamic stiffness measured in HYAFF 1 -M-based constructs also increased with time, up to, respectively, 1.3-and 16-fold. This study demonstrates the feasibility to engineer goat cartilaginous tissues at different stages of development by varying culture time, and thus opens the possibility to test the effect of maturation stage of engineered cartilage on the outcome of cartilage repair in orthotopic goat models. ß

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Section: Discussionmentioning

confidence: 93%

Cartilage tissue engineering by expanded goat articular chondrocytes

Miot

Freitas

Wirz

et al. 2006

Journal Orthopaedic Research

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“…However, in human diseases restricted to the articular cartilage, such as chondromalacia patellae, intense cell proliferation has been reported in the lesions as well as in the surrounding cartilage (35), which suggests that articular cartilage may contain resident cells that are sensitive to environmental cues and responsive to cartilage damage. Recently, Barbero et al reported that dedifferentiated adult human articular chondrocytes exhibited a differentiation plasticity (chondrocytic, osteoblastic, and adipocytic lineages), which was modulated by growth factors used during monolayer expansion and was highly heterogeneous across different clones (13).…”

Section: Discussionmentioning

confidence: 99%

“…Dedifferentiated chondrocytes are able to redifferentiate toward the chondrogenic lineage and to reexpress a chondrocytic phenotype when cultured in suspension, in agarose, with alginate beads, or on a hydrogel substrate in vitro (8,(11)(12)(13)(14)(15). Subcutaneous implantation of such dedifferentiated chondrocytes into the joints of nude mice can lead to redifferentiation, which is expressed by formation of cartilage nodules (16).…”

mentioning

confidence: 99%

Articular cartilage repair using dedifferentiated articular chondrocytes and bone morphogenetic protein 4 in a rabbit model of articular cartilage defects

Lin¹,

Zhou²,

Wei³

et al. 2008

Arthritis & Rheumatism

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Objective. To observe redifferentiation of dedifferentiated chondrocytes after transplantation into the joint, and to evaluate the ability of dedifferentiated chondrocytes transduced with adenovirus containing bone morphogenetic protein 4 (BMP-4) to redifferentiate in vitro and in vivo in a rabbit model of articular cartilage defects.Methods. Monolayer and pellet culture systems were used to evaluate the redifferentiation of dedifferentiated chondrocytes transduced with BMP-4. A rabbit model of partial-thickness articular cartilage defects was used to evaluate cartilage repair macroscopically and histologically, 6 and 12 weeks after transplantation with first-passage, fifth-passage, or transduced fifthpassage chondrocytes. Histologic grading of the repaired tissue was performed. Expression of BMP-4 and the ability of transplanted cells to recover a chondrocytic phenotype were also assessed. Conclusion. Some dedifferentiated chondrocytes can redifferentiate after transplantation into the loadbearing joint. BMP-4 can be used to induce redifferentiation of dedifferentiated chondrocytes in vitro and in vivo, which could help enhance articular cartilage repair. Results. BMP-4-expressing dedifferentiated

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“…In vitro differentiation was induced as previously described [19][20][21]. See Materials and Methods in Supporting Information.…”

Section: In Vitro Differentiationmentioning

confidence: 99%

Fibroblast Growth Factor-2 Maintains a Niche-Dependent Population of Self-Renewing Highly Potent Non-adherent Mesenchymal Progenitors Through FGFR2c

et al. 2012

Self Cite

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Bone marrow (BM) mesenchymal stem/stromal cells (MSC) are a heterogeneous population of multipotent progenitors currently under investigation for a variety of applications in regenerative medicine. While self-renewal of stem cells in different tissues has been demonstrated to be regulated by specialized microenvironments called niches, it is still unclear whether a self-renewing niche also exists for MSC. Here, we show that primary human BM cultures contain a population of intrinsically non-adherent mesenchymal progenitors (NAMP) with features of more primitive progenitors than the initially adhering colonyforming units-fibroblast (CFU-f). In fact, NAMP could generate an adherent progeny: (a) enriched with early mesenchymal populations (CD1461, SSEA-11, and SSEA-41); (b) with significantly greater proliferation and multilineage differentiation potential in vitro; and (c) capable of threefold greater bone formation in vivo than the corresponding CFU-f. Upon serial replating, NAMP were able to regenerate and expand in suspension as non-adherent clonogenic progenitors, while also giving rise to an adherent progeny. This took place at the cost of a gradual loss of proliferative potential, shown by a reduction in colony size, which could be completely prevented when NAMP were expanded on the initially adhering BM fraction. Mechanistically, we found that NAMP crucially depend on fibroblast growth factor (FGF)-2 signaling through FGFR2c for their survival and expansion. Furthermore, NAMP maintenance depends at least in part on humoral signals distinct from FGF-2. In conclusion, our data show a niche/progenitor organization in vitro, in which the BM adherent fraction provides a self-renewing microenvironment for primitive NAMP.

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Plasticity of clonal populations of dedifferentiated adult human articular chondrocytes

Cited by 344 publications

References 42 publications

Cartilage tissue engineering by expanded goat articular chondrocytes

Cartilage tissue engineering by expanded goat articular chondrocytes

Articular cartilage repair using dedifferentiated articular chondrocytes and bone morphogenetic protein 4 in a rabbit model of articular cartilage defects

Fibroblast Growth Factor-2 Maintains a Niche-Dependent Population of Self-Renewing Highly Potent Non-adherent Mesenchymal Progenitors Through FGFR2c

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