ArticlePloS one2008
Replicative senescence of mesenchymal stem cells: a continuous and organized process.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 572 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
572 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,109 citations in OpenAlex.
- A Comparison of the Properties of Mesenchymal Stem Cells Derived from Different Synovial Sources: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.The Cochrane database of systematic reviews · 2020Pooled it
- Mesenchymal stem/stromal cell senescence in aging and regenerative medicine: a systematic review.Biogerontology · 2026Review
- Alternative Splicing Constitutes a Transcription-independent Regulatory Layer in Replicative Senescence of Human Umbilical Cord Mesenchymal Stem Cells.Stem cell reviews and reports · 2026Article
- Enhancing the Scalable Manufacturing of Human Mesenchymal Stromal Cells in Dynamic Culture Using Bioactive Heparin/Collagen Layer-by-Layer Coated Microcarriers.Biotechnology journal · 2026Article
- Article
- Serum-induced recovery of proliferative capacity and differentiation potential in aged dental pulp stem cells.Stem cells translational medicine · 2026Article
- Exploring Stem Cell Based Senotherapeutic Strategies for Targeting Cellular Senescence in Brain Aging.Stem cell reviews and reports · 2026Review
- An ITGA11 expressing subpopulation as predictor for the donor-specific osteogenic capacity of stromal cells.Bone research · 2026Article
- Lineage topology, replication kinetics and cell cycle synchronization reveal regulated growth dynamics in human bone marrow stromal cell colonies.Scientific reports · 2026Article
- Inheritance entropy: A model-independent method to probe the hereditary structure of cell lineage trees.PRX life · 2026Article
- Prolonged high-density culture with restricted medium renewal induces epithelial-like plasticity in apical papilla stem cells.Biomolecules & biomedicine · 2026Article
- Shear-Induced CROSS (Cellular RedOx Spreading Shield) Assembly Sustains Neurotrophic Extracellular Vesicle Production for Functional Neural Networks.Advanced functional materials · 2026Article
- Fibroblast-Based Cell Therapy: Molecular Background, Current Therapies and Future Perspectives.Cells · 2026Review
- Immortalized Rat Tendon-Derived Stem Cells for Tendon Tissue Engineering.Bioengineering (Basel, Switzerland) · 2026Article
- Pneumatospinning and Electrospinning Scaffolds for Meniscus Regeneration Using Human Embryonic-Derived Mesenchymal Stem Cells.Bioengineering (Basel, Switzerland) · 2026Article
- Pretreated mesenchymal stromal cells and their secretome for kidney disease: mechanisms and applications.Stem cell research & therapy · 2026Review
- Bioreactors expansion of human mesenchymal stromal cell therapies: platforms, parameters, challenges and opportunities.Journal, genetic engineering & biotechnology · 2026Review
- Senescence profiling and biomarker identification in cell product based on adipose tissue-derived mesenchymal stromal cells.Stem cells translational medicine · 2026Article
- A microneedle platform Co-encapsulating chondral organoids and PpIX for spatiotemporally orchestrated tumor ablation and osteochondral regeneration.Bioactive materials · 2026Article
512 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSC) comprise a promising tool for cellular therapy. These cells are usually culture expanded prior to their application. However, a precise molecular definition of MSC and the sequel of long-term in vitro culture are yet unknown. In this study, we have addressed the impact of replicative senescence on human MSC preparations. Within 43 to 77 days of cultivation (7 to 12 passages), MSC demonstrated morphological abnormalities, enlargement, attenuated expression of specific surface markers, and ultimately proliferation arrest. Adipogenic differentiation potential decreased whereas the propensity for osteogenic differentiation increased. mRNA expression profiling revealed a consistent pattern of alterations in the global gene expression signature of MSC at different passages. These changes are not restricted to later passages, but are continuously acquired with increasing passages. Genes involved in cell cycle, DNA replication and DNA repair are significantly down-regulated in late passages. Genes from chromosome 4q21 were over-represented among differentially regulated transcripts. Differential expression of 10 genes has been verified in independent donor samples as well as in MSC that were isolated under different culture conditions. Furthermore, miRNA expression profiling revealed an up-regulation of hsa-mir-371, hsa-mir-369-5P, hsa-mir-29c, hsa-mir-499 and hsa-let-7f upon in vitro propagation. Our studies indicate that replicative senescence of MSC preparations is a continuous process starting from the first passage onwards. This process includes far reaching alterations in phenotype, differentiation potential, global gene expression patterns, and miRNA profiles that need to be considered for therapeutic application of MSC preparations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.