Comparative analysis of neuroectodermal differentiation capacity of human bone marrow stromal cells using various conversion protocols
| Autor: | Hans-Jörg Habisch, Regina Gastl, Jörg Fiedler, Stefan Liebau, Stefan Fickert, Johannes Schwarz, Andreas Hermann, Alexander Storch, Rolf E. Brenner |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
endocrine system Pathology medicine.medical_specialty animal structures Stromal cell Adolescent Population Cell Culture Techniques Bone Marrow Cells Nerve Tissue Proteins Neuroectodermal Cell Germ layer Biology Epigenesis Genetic Cellular and Molecular Neuroscience Ectoderm medicine Humans Cell Lineage RNA Messenger education Neural cell Cells Cultured Neurons education.field_of_study Reverse Transcriptase Polymerase Chain Reaction Multipotent Stem Cells Transdifferentiation Mesenchymal stem cell Gene Expression Regulation Developmental Cell Differentiation Nestin Immunohistochemistry Cell biology embryonic structures Stromal Cells Neuroglia Biomarkers |
| Zdroj: | Journal of Neuroscience Research. 83:1502-1514 |
| ISSN: | 1097-4547 0360-4012 |
| DOI: | 10.1002/jnr.20840 |
| Popis: | Human adult bone marrow-derived mesodermal stromal cells (hMSCs) are able to differentiate into multiple mesodermal tissues, including bone and cartilage. There is evidence that these cells are able to break germ layer commitment and differentiate into cells expressing neuroectodermal properties. There is still debate about whether this results from cell fusion, aberrant marker gene expression or real neuroectodermal differentiation. Here we extend our work on neuroectodermal conversion of adult hMSCs in vitro by evaluating various epigenetic conversion protocols using quantitative RT-PCR and immunocytochemistry. Undifferentiated hMSCs expressed high levels of fibronectin as well as several neuroectodermal genes commonly used to characterize neural cell types, such as nestin, beta-tubulin III, and GFAP, suggesting that hMSCs retain the ability to differentiate into neuroectodermal cell types. Protocols using a direct differentiation of hMSCs into a neural phenotype failed to induce significant changes in morphology and/or expression of markers of early and mature glial/neuronal cells types. In contrast, a multistep protocol with conversion of hMSCs into a neural stem cell-like population and subsequent terminal differentiation in mature glia and neurons generated relevant morphological changes as well as significant increase of expression levels of marker genes for early and late neural cell types, such as nestin, neurogenin2, MBP, and MAP2ab, accompanied by a loss of their mesenchymal properties. Our data provide an impetus for differentiating hMSCs in vitro into mature neuroectodermal cells. Neuroectodermally converted hMSCs may therefore ultimately help in treating acute and chronic neurodegenerative diseases. Analysis of marker gene expression for characterization of neural cells derived from MSCs has to take into account that several early and late neuroectodermal genes are already expressed in undifferentiated MSCs. |
| Databáze: | OpenAIRE |
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