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Ranieri Cancedda

Publications and source records attributed to Ranieri Cancedda.

39 records · Page 3Linked to original sources

Mice Drawer System: phase c/d development and perspective.

MDS (Mice Drawer System) is the Facility that will support the research on board the International Space Station (ISS). Funded by ASI with Laben as industrial Prime Contractor, MDS will also permit its utilisation for other research programs with mice. The most attractive feature of MDS is that six mice can he kept separate inside dedicated and isolated cages. This permits to perform six experiments in parallel, one for each mouse. In the first utilisation flight of MDS facility the selected experiment is devoted to study human bone formation and specific countermeasures to prevent osteoporosis using mice under microgravity conditions as a model.

Journal Article↗

Serum-free growth medium sustains commitment of human articular chondrocyte through maintenance of Sox9 expression.

Human articular cartilage heals poorly in adults and current surgical procedures do not provide long-term repair. Cell therapy and tissue engineering could become the treatment of choice, but suffer a major limitation as chondrocytes in vitro lose the differentiated phenotype. In vivo, the chondrogenic lineage is specified by transcription factor Sox9. Thus, cell-based therapy could be successful if Sox9 expression and chondrogenic commitment of the expanded cells were preserved. To achieve this goal, we developed a serum-free medium that supports cell proliferation and preserves the differentiation potential. Indeed, expression of Sox9 is maintained when the conventionally used serum is substituted for by this defined supplement. Spontaneous cartilage formation after expansion in serum-free medium is obtained in vitro in a high-density pellet culture and confirmed in vivo in a functional assay in immunodeficient mice. By contrast, cells grown in serum lose the expression of Sox9 and fail to reform cartilage both in vitro and in vivo unless they are rescued by chondrogenic inducers such as transforming growth factor beta(1) and dexamethasone. Our data emphasize the importance of the microenvironment in modulating commitment, plasticity, and phenotype of chondrocytes, and provide an experimental system to study their physiological or pathological metabolism in a controlled context.

Adolescent↗

Species variability in the differentiation potential of in vitro-expanded articular chondrocytes restricts predictive studies on cartilage repair using animal models.

Autologous chondrocyte implantation is currently applied in clinics as an innovative tool for articular cartilage repair. Animal models have been and still are being used to validate and further improve the technique. However, in various species, the outcome varies from hyaline-like cartilage to fibrocartilage. This may be due partly to the spontaneous dedifferentiation of chondrocytes once cultured in vitro. Here we assessed whether the extent of dedifferentiation varies between species and we hypothesized that the level of chondrocyte phenotype stability during expansion may contribute to the maintenance of their chondrogenic commitment and redifferentiation potential. Condyle chondrocytes were harvested from sheep, dog, and human, and expanded for 1, 6, or 12 cell duplications. At each interval, cell phenotype was monitored (morphology and biosynthesis of cartilage markers) and redifferentiation was assessed by an in vitro assay of chondrogenesis in micromass pellet and an in vivo assay of ectopic cartilage formation in immunodeficient mice. Results indicate that, during culture, the sheep chondrocyte phenotype is maintained better than that of human chondrocytes, which in turn dedifferentiate to a lesser extent than dog chondrocytes Accordingly, after expansion, sheep chondrocytes spontaneously reform hyaline-like cartilage; human chondrocytes redifferentiate only under stimulation with chondrogenic inducers whereas, after a few passages, dog chondrocytes lose any capacity to redifferentiate regardless of the presence of inducers. Thus, conditions allowing cartilage formation in one species are not necessarily transposable to other species. Therefore, results with animal models should be cautiously applied to humans. In addition, for tissue-engineering purposes, the number of cell duplications must be, for each species, carefully monitored to remain in the range of amplification allowing redifferentiation and chondrogenesis.

Animals↗