Unknown,Transcriptomics,Genomics,Proteomics

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Surface Topography Enhances Differentiation of Mesenchymal Stem Cells Towards Osteogenic and Adipogenic Lineages

ABSTRACT: Surface topography impacts on cell growth and differentiation, but it is not trivial to generate homogeneous surface structures and to define the specific morphological parameters of relevance. In this study, we have compared gene expression profiles of mesenchymal stem cells (MSCs) on nanostructured groove/ridge surfaces. Patterns were generated in polyimide using multi beam laser interference. These structures affected cell size and orientation of human MSCs. Furthermore, the nano-patterns with a periodicity of 650 nm increased differentiation towards osteogenic and adipogenic lineages. However, in absence of differentiation media the surface structures did neither induce differentiation, nor lineage-specific gene expression changes – as assessed by genome wide gene expression profiles with Affymetrix microarray technology. Our results demonstrate that grooves and ridges at a periodicity of 650 nm enhance the propensity of MSCs to differentiate towards adipogenic and/or osteogenic lineages – but they do not directly govern lineage-specific gene expression changes. 9 samples were hybridized to the GeneChip Human Gene 2.0 ST Array (Affymetrix). In comparison to the manuscript the donor IDs refer as follows: donor 1 = AT57; donor 2 = AT58; donor 3 = AT61.

ORGANISM(S): Homo sapiens

SUBMITTER: Wolfgang Wagner

PROVIDER: E-GEOD-61113 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages.

Abagnale Giulio G Steger Michael M Nguyen Vu Hoa VH Hersch Nils N Sechi Antonio A Joussen Sylvia S Denecke Bernd B Merkel Rudolf R Hoffmann Bernd B Dreser Alice A Schnakenberg Uwe U Gillner Arnold A Wagner Wolfgang W

Biomaterials 20150518

Surface topography impacts on cell growth and differentiation, but it is not trivial to generate defined surface structures and to assess the relevance of specific topographic parameters. In this study, we have systematically compared in vitro differentiation of mesenchymal stem cells (MSCs) on a variety of groove/ridge structures. Micro- and nano-patterns were generated in polyimide using reactive ion etching or multi beam laser interference, respectively. These structures affected cell spreadi ...[more]

PMID: 26026844

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Project description:We have previously reported that the deficiency of p53 alone or in combination with Rb (Rb-/- p53-/-) in adipose-derived MSCs (ASCs) promotes leiomyosarcoma-like tumors in vivo. Here, we hypothesized that the source of MSCs and/or the cell differentiation stage could determine the phenotype of sarcoma development. To investigate whether there is a link between the source of MSCs and sarcoma phenotype, we generated p53-/- and Rb-/-p53-/- MSCs from bone marrow (BM-MSCs). Both genotypes of BM-MSCs initiated leiomyosarcoma formation similar to p53-/- and Rb-/-p53-/- ASCs. In addition, gene expression profiling revealed a link between p53- or Rb-p53-deficient BM-MSCs and ASCs and muscle-associated sarcomagenesis. These data suggest that the tissue source of MSC does not seem a crucial factor in the development of a particular sarcoma phenotype. To analyze whether the differentiation stage defines the sarcoma phenotype, BM-MSCs and ASCs were induced to differentiate towards the osteogenic lineage, and both p53 and Rb were excised using Cre-expressing adenovectors at different stages along osteogenic differentiation. Regardless of the level of osteogenic commitment, the inactivation of Rb and p53 in BM-MSC-derived, but not in ASC-derived, osteogenic progenitors gave rise to osteosarcoma-like tumors which could be serially transplanted. This indicates that the osteogenic differentiation stage of BM-MSCs imposes the phenotype of in vivo sarcoma development, and that BM-MSC-derived osteogenic progenitors rather than undifferentiated BM-MSCs, undifferentiated ASCs or ASC-derived osteogenic progenitors, represent the cell of origin for osteosarcoma development. To analyse whether the BM-MSC and Fat-MSC (ASC) differentiation stage may define the sarcoma phenotype, RbloxP/loxPp53loxP/loxP BM-MSCs and ASCs were induced to differentiate towards the osteogenic lineage and both Rb and p53 were excised with adenoviral vectors expressing the Cre-recombinase gene (Ad-CMV-Cre) at different stages (day 0 and 10) along osteogenic differentiation. NSG mice were inoculated subcutaneously with 5M-CM-^W10^6 mutant cells. Animals were killed when tumors reached 1 cm3 or 150 days after infusion. Some of the obtained tumors were mechanically disaggregated to establish ex vivo MSC-transformed cell lines. Gene expression analysis was performed using: WT BM-MSCs and ASCs, Rb-/-p53-/- BM-MSCs and ASCs previously differentiated to the osteogenic lineage for 10 days and a tumor cell line derived from p53-/-Rb-/- BM-MSC differentiated to the osteogenic lineage for 10 days.

Dataset Information

Surface Topography Enhances Differentiation of Mesenchymal Stem Cells Towards Osteogenic and Adipogenic Lineages

Publications

Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages.

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