ArticleStem cells translational medicine2019
Accumulating Transcriptome Drift Precedes Cell Aging in Human Umbilical Cord-Derived Mesenchymal Stromal Cells Serially Cultured to Replicative Senescence.
Article in Stem cells translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Alternative Splicing Constitutes a Transcription-independent Regulatory Layer in Replicative Senescence of Human Umbilical Cord Mesenchymal Stem Cells.Stem cell reviews and reports · 2026Article
- Beyond Passage Numbers: How Culture Conditions and Population-Doubling Metrics Reporting Shape the Quality of Umbilical Cord-Derived MSCs and Extracellular Vesicles.International journal of molecular sciences · 2026Review
- Research Advances on Mesenchymal Stem Cell-Derived Exosomes in Anti-Graft-Versus-Host Disease Therapy: Mechanisms, Therapeutic Potential, and Future Prospects.International journal of molecular sciences · 2026Review
- Comparative Transcriptomic Profiling of Mesenchymal Stem Cells from Distinct Tissue Origins and Isolation Methods Highlights the Stability and Immunomodulatory Signature of Umbilical Cord-Derived Smumf Cells.Tissue engineering and regenerative medicine · 2026Article
- An animal component-free bioprocess for synthesizing 3D human matrix scaffolds using mesenchymal stromal cells.Frontiers in cell and developmental biology · 2026Article
- Impacts of Inorganic Arsenic Exposure on Genetic Stability of Human Mesenchymal Stromal Cells.Journal of applied toxicology : JAT · 2025Article
- A Mathematical Model for Determining Probabilistic Design Space in Mesenchymal Stem Cell Passage Culture.Biotechnology and bioengineering · 2025Article
- Macromolecular Crowding for Reparative Medicine and Drug Discovery Applications.Sub-cellular biochemistry · 2025Review
- A milestone for the therapeutic EV field: FDA approves Ryoncil, an allogeneic bone marrow-derived mesenchymal stromal cell therapy.Extracellular vesicles and circulating nucleic acids · 2025Article
- Article
- Development of Biomimetic Substrates for Limbal Epithelial Stem Cells Using Collagen-Based Films, Hyaluronic Acid, Immortalized Cells, and Macromolecular Crowding.Life (Basel, Switzerland) · 2024Article
- Machine learning-based morphological quantification of replicative senescence in human fibroblasts.GeroScience · 2024Article
- Gums as Macromolecular Crowding Agents in Human Skin Fibroblast Cultures.Life (Basel, Switzerland) · 2024Article
- Efficient expansion and delayed senescence of hUC-MSCs by microcarrier-bioreactor system.Stem cell research & therapy · 2023Article
- Clinical Prospect of Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles in Kidney Disease: Challenges and the Way Forward.Pharmaceutics · 2023Review
- Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success.Cellular & molecular immunology · 2023Review
- Chromatographic Scalable Method to Isolate Engineered Extracellular Vesicles Derived from Mesenchymal Stem Cells for the Treatment of Liver Fibrosis in Mice.International journal of molecular sciences · 2023Article
- BMP9 reduces age-related bone loss in mice by inhibiting osteoblast senescence through Smad1-Stat1-P21 axis.Cell death discovery · 2022Article
- Article
- Comparative Effects of Bone Marrow-derived Versus Umbilical Cord Tissue Mesenchymal Stem Cells in an Experimental Model of Bronchopulmonary Dysplasia.Stem cells translational medicine · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In preclinical studies, mesenchymal stromal cells (MSCs) exhibit robust potential for numerous applications. To capitalize on these benefits, cell manufacturing and delivery protocols have been scaled up to facilitate clinical trials without adequately addressing the impact of these processes on cell utility nor inevitable regulatory requirements for consistency. Growing evidence indicates that culture-aged MSCs, expanded to the limits of replicative exhaustion to generate human doses, are not equivalent to early passage cells, and their use may underpin reportedly underwhelming or inconsistent clinical outcomes. Here, we sought to define the maximum expansion boundaries for human umbilical cord-derived MSCs, cultured in chemically defined xeno- and serum-free media, that yield consistent cell batches comparable to early passage cells. Two male and two female donor populations, recovered from cryostorage at mean population doubling level (mPDL) 10, were serially cultivated until replicative exhaustion (senescence). At each passage, growth kinetics, cell morphology, and transcriptome profiles were analyzed. All MSC populations displayed comparable growth trajectories through passage 9 (P9; mPDL 45) and variably approached senescence after P10 (mPDL 49). Transcription profiles of 14,500 human genes, generated by microarray, revealed a nonlinear evolution of culture-adapted MSCs. Significant expression changes occurred only after P5 (mPDL 27) and accumulated rapidly after P9 (mPDL 45), preceding other cell aging metrics. We report that cryobanked umbilical cord-derived MSCs can be reliably expanded to clinical human doses by P4 (mPDL 23), before significant transcriptome drift, and thus represent a mesenchymal cell source suited for clinical translation of cellular therapies. Stem Cells Translational Medicine 2019;8:945&958.
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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.