MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors.

The ability of human mesenchymal stromal/stem cells (hMSCs) to differentiate into various mesenchymal cell lineages makes them a promising cell source for the use in tissue repair strategies. Since the differentiation potential of hMSCs differs between donors, it is necessary to establish biomarkers for the identification of donors with high differentiation potential. In this study, we show that microRNA (miRNA) expression levels are effective for distinguishing donors with high differentiation potential from low differentiation potential.

Differentiation of mesenchymal stem cells under hypoxia and normoxia: lipid profiles revealed by time-of-flight secondary ion mass spectrometry and multivariate analysis.

Mesenchymal stem cells (MSC) have the ability to self-renew and differentiate into multiple cell types valuable for clinical treatment of rheumatic pathologies. To study the chondrogenic potential of MSC and identify the conditions that recreate the native cartilage environment, we used time-of-flight secondary ion mass spectrometry (TOF-SIMS) for label-free detection of cell-type- and environmental-condition-specific molecular profiles. We observed that coculture of human MSC and chondrocytes under standard culture conditions leads to improved extracellular matrix (ECM) deposition.

O-Phenanthroline as modulator of the hypoxic and catabolic response in cartilage tissue-engineering models.

Hypoxia has been shown to be important for maintaining cartilage homeostasis as well as for inducing chondrogenic differentiation. Ensuring low oxygen levels during in vitro culture is difficult, therefore we assessed the chondro-inductive capabilities of the hypoxia-mimicking agent O-phenanthroline, which is also known as a non-specific matrix metalloproteinase (MMP) inhibitor. We found that O-phenanthroline reduced the expression of MMP3 and MMP13 mRNA levels during chondrogenic differentiation of human chondrocytes (hChs), as well as after TNFα/IL-1β exposure in an explant model.

Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate.

Actively steering the chondrogenic differentiation of mesenchymal stromal cells (MSCs) into either permanent cartilage or hypertrophic cartilage destined to be replaced by bone has not yet been possible. During limb development, the developing long bone is exposed to a concentration gradient of oxygen, with lower oxygen tension in the region destined to become articular cartilage and higher oxygen tension in transient hypertrophic cartilage. Here, we prove that metabolic programming of MSCs by oxygen tension directs chondrogenesis into either permanent or transient hyaline cartilage.

Mesenchymal stromal/stem cell-or chondrocyte-seeded microcarriers as building blocks for cartilage tissue engineering.

In this study we have tested the use of mesenchymal stromal/stem cell (MSC)- or chondrocyte (hch)-laden microcarriers as building blocks for engineered cartilage tissue. MSCs and hchs expanded on microcarriers were used in chondrogenic coculture and compared with monoculture of MSCs or hchs. The use of cell-laden microcarriers as building blocks for cartilage tissue engineering led to a compact tissue formation with significant volume increase compared to the biomaterial-free approach.

GREM1, FRZB and DKK1 mRNA levels correlate with osteoarthritis and are regulated by osteoarthritis-associated factors.

Introduction: Osteoarthritis is, at least in a subset of patients, associated with hypertrophic differentiation of articular chondrocytes. Recently, we identified the bone morphogenetic protein (BMP) and wingless-type MMTV integration site (WNT) signaling antagonists Gremlin 1 (GREM1), frizzled-related protein (FRZB) and dickkopf 1 homolog (Xenopus laevis) (DKK1) as articular cartilage's natural brakes of hypertrophic differentiation. In this study, we investigated whether factors implicated in osteoarthritis or regulation of chondrocyte hypertrophy influence GREM1, FRZB and DKK1 expression levels.

The effect of donor variation and senescence on endothelial differentiation of human mesenchymal stromal cells.

Application of autologous cells is considered for a broad range of regenerative therapies because it is not surrounded by the immunological and ethical issues of allo- or xenogenic cells. However, isolation, expansion, and application of autologous cells do suffer from variability in therapeutic efficacy due to donor to donor differences and due to prolonged culture. One important source of autologous cells is mesenchymal stromal cells (MSCs), which can differentiate toward endothelial-like cells, thus making them an ideal candidate as cell source for tissue vascularization.

Nanostructured 3D constructs based on chitosan and chondroitin sulphate multilayers for cartilage tissue engineering.

Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH).

Cell sources for articular cartilage repair strategies: shifting from monocultures to cocultures.

The repair of articular cartilage is challenging due to the sparse native cell population combined with the avascular and aneural nature of the tissue. In recent years, cartilage tissue engineering has shown great promise. As with all tissue engineering strategies, the possible therapeutic outcome is intimately linked with the used combination of cells, growth factors, and biomaterials.

Cartilage tissue engineering.

Cartilage tissue engineering is the art aimed at repairing defects in the articular cartilage which covers the bony ends in the joints. Since its introduction in the early 1990s of the past century, cartilage tissue engineering using ACI has been used in thousands of patients to repair articular cartilage defects. This review focuses on emerging strategies to improve cartilage repair by incorporating fundamental knowledge of developmental and cell biology in the design of optimized strategies for cell delivery at the defect site and to locally stimulate cartilage repair responses.

Trophic effects of mesenchymal stem cells increase chondrocyte proliferation and matrix formation.

Previous studies showed that coculture of primary chondrocytes (PCs) with various sources of multipotent cells results in a higher relative amount of cartilage matrix formation than cultures containing only chondrocytes. The aim of this study was to investigate the mechanism underlying this observation. We used coculture pellet models of human mesenchymal stem cells (hMSCs) and human PCs or bovine PCs (bPCs) and studied the fate and the contribution to cartilage formation of the individual cell populations during coculture.

Strategies for zonal cartilage repair using hydrogels.

Articular cartilage is a highly hydrated tissue with depth-dependent cellular and matrix properties that provide low-friction load bearing in joints. However, the structure and function are frequently lost and there is insufficient repair response to regenerate high-quality cartilage. Several hydrogel-based tissue-engineering strategies have recently been developed to form constructs with biomimetic zonal variations to improve cartilage repair.

Morphological variation and airflow dynamics in the human nose.

Airflow dynamics are recognized as being important to the functioning of the human nose in conditioning and filtering inspired air, yet these dynamics are poorly understood. Despite considerable research on airflow dynamics by otolaryngologists, respiratory physiologists, and toxicologists, major disagreements remain about the nature of airflow in the human nose. Specifically, there is little consensus about the character of nasal airflow regimes (laminar or turbulent) and about the major pathways of airflow through the internal chamber.