Neurogenic potential of human mesenchymal stem cells revisited: analysis by immunostaining, time-lapse video and microarray
| Autor: | Giorgia Volpi, N. Bertani, Roberto Perris, Paolo Sonego, Paolo Malatesta |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Time Factors Transcription Genetic Biology Stem cell marker Immunophenotyping Cancer stem cell Neurosphere Humans Cell Lineage Cell Shape Oligonucleotide Array Sequence Analysis Stem cell transplantation for articular cartilage repair Neurons Microscopy Video Gene Expression Profiling Cell Differentiation Mesenchymal Stem Cells Cell Biology Middle Aged Immunohistochemistry Neural stem cell Cell biology Phenotype Gene Expression Regulation Amniotic epithelial cells Immunology Stem cell Biomarkers Adult stem cell |
| Zdroj: | Journal of Cell Science. 118:3925-3936 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | The possibility of generating neural cells from human bone-marrow-derived mesenchymal stem cells (hMSCs) by simple in vitro treatments is appealing both conceptually and practically. However, whether phenotypic modulations observed after chemical manipulation of such stem cells truly represent a genuine trans-lineage differentiation remains to be established. We have re-evaluated the effects of a frequently reported biochemical approach, based on treatment with butylated hydroxyanisole and dimethylsulphoxide, to bring about such phenotypic conversion by monitoring the morphological changes induced by the treatment in real time, by analysing the expression of phenotype-specific protein markers and by assessing the modulation of transcriptome. Video time-lapse microscopy showed that conversion of mesenchymal stem cells to a neuron-like morphology could be reproduced in normal primary fibroblasts as well as mimicked by addition of drugs eliciting cytoskeletal collapse and disruption of focal adhesion contacts. Analysis of markers revealed that mesenchymal stem cells constitutively expressed multi-lineage traits, including several pertaining to the neural one. However, the applied `neural induction' protocol neither significantly modulated the expression of such markers, nor induced de novo translation of other neural-specific proteins. Similarly, global expression profiling of over 21,000 genes demonstrated that gene transcription was poorly affected. Most strikingly, we found that the set of genes whose expression was altered by the inductive treatment did not match those sets of genes differentially expressed when comparing untreated mesenchymal stem cells and immature neural tissues. Conversely, by comparing these gene expression profiles with that obtained from comparisons between the same cells and an unrelated non-neural organ, such as liver, we found that the adopted neural induction protocol was no more effective in redirecting human mesenchymal stem cells toward a neural phenotype than toward an endodermal hepatic pathway. |
| Databáze: | OpenAIRE |
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