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Background Nidogen-2, an extracellular matrix protein, is ubiquitous in renal basement membranes linking the laminin and collagen IV networks. Nidogen-2-deficient (nidogen-2−/–) mice do not exhibit a phenotype, and renal basement membranes appear normal. The functional role of nidogen-2 in the adult kidney under pathological conditions however remains unclear. We tested the hypothesis that nidogen-2 mediated cell-matrix interactions are important to maintain glomerular integrity and structure in renal hyperperfusion and hypertension. Materials and methods Two weeks after unilateral nephrectomy (UNX), desoxycorticosterone (DOCA)-salt hypertension was induced in nidogen-2−/– mice and their wild type littermates for 6 weeks. Renal damage was assessed by means of semiquantitative scoring, morphometric analysis, immunohistochemistry and measurement of serum creatinine and albumin excretion. Results UNX alone resulted in a very mild increase in renal damage in nidogen-2−/– mice compared to wild type animals. Following DOCA-salt treatment, blood pressure, serum creatinine and albumin excretion were significantly higher in nidogen-2−/– than in wild type mice. In addition, nidogen-2−/– mice showed increased mesangial cell hyperplasia and matrix expansion with higher expression of fibronectin and its receptor α8 integrin. Glomerular capillaries were significantly reduced in size and number. Conclusions We demonstrate that in both mild and severe glomerular damage, lack of nidogen-2 is associated with: (i) increased mesangioproliferation; (ii) higher mesangial matrix expansion; and (iii) reduction in glomerular capillary supply. These findings suggest a critical role for nidogen-2 in the maintenance of glomerular structure in the diseased kidney. [ABSTRACT FROM AUTHOR]

The author comments on the scientific and editorial work of Professor Hermann Neels on the occasion of the 100th anniversary of his birthday.

Objective: To compare the chondrogenic potential of human bone marrow-derived mesenchymal stem cells (BMSC) and adipose tissue-derived stromal cells (ATSC), because the availability of an unlimited cell source replacing human chondrocytes could be strongly beneficial for cell therapy, tissue engineering, in vitro drug screening, and development of new therapeutic options to enhance the regenerative capacity of human cartilage., Methods: Quantitative gene expression of common cartilage and cell interaction molecules was analyzed using complementary DNA array technology and reverse transcription-polymerase chain reaction during optimization of cell differentiation, in order to achieve a molecular phenotype similar to that of chondrocytes in cartilage., Results: The multilineage potential of BMSC and ATSC was similar according to cell morphology and histology, but minor differences in marker gene expression occurred in diverse differentiation pathways. Although chondrogenic differentiation of BMSC and ATSC was indistinguishable in monolayer and remained partial, only BMSC responded (with improved chondrogenesis) to a shift to high-density 3-dimensional cell culture, and reached a gene expression profile highly homologous to that of osteoarthritic (OA) cartilage., Conclusion: Hypertrophy of chondrocytes and high matrix-remodeling activity in differentiated BMSC spheroids and in OA cartilage may be the basis for the strong similarities in gene expression profiles between these samples. Differentiated stem cell spheroids represent an attractive tool for use in drug development and identification of drug targets in OA cartilage-like tissue outside the human body. However, optimization of differentiation protocols to achieve the phenotype of healthy chondrocytes is desired for cell therapy and tissue engineering approaches.