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Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Replicative senescence of mesenchymal stem cells: a continuous and organized process
Wolfgang Wagner1, Patrick Horn, Mirco Castoldi
1Department of Medicine V, University of Heidelberg, Heidelberg, Germany. wolfgang_wagner@med.uni-heidelberg.de
Plos One
|May 22, 2008
Summary
Long-term culture of mesenchymal stem cells (MSC) causes continuous replicative senescence, altering their phenotype, differentiation, and gene expression. These changes impact their therapeutic potential.
Area of Science:
- Cell Biology
- Regenerative Medicine
- Stem Cell Biology
Background:
- Mesenchymal stem cells (MSC) are vital for cellular therapy but require in vitro expansion.
- The molecular definition and effects of long-term culture on MSC remain unclear.
Purpose of the Study:
- To investigate the impact of replicative senescence on human MSC during prolonged in vitro cultivation.
- To characterize molecular and phenotypic changes in MSC with increasing passages.
Main Methods:
- Human MSC were cultured for 43–77 days (7–12 passages).
- Morphological, surface marker expression, and differentiation potential (adipogenic, osteogenic) were assessed.
- mRNA and miRNA expression profiling was performed at different passages.
Main Results:
- MSC exhibited morphological changes, reduced surface marker expression, and proliferation arrest with senescence.
- Adipogenic potential decreased, while osteogenic potential increased.
- Significant alterations in global gene expression, including downregulation of cell cycle/DNA repair genes, and specific miRNA upregulation (e.g., hsa-mir-371) were observed.
Conclusions:
- Replicative senescence is a continuous process in MSC starting from early passages.
- Senescence induces profound changes in MSC phenotype, differentiation, gene, and miRNA profiles.
- These senescence-induced alterations must be considered for therapeutic applications of MSC.
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