ArticleStem cells (Dayton, Ohio)2013
Dynamic compaction of human mesenchymal stem/precursor cells into spheres self-activates caspase-dependent IL1 signaling to enhance secretion of modulators of inflammation and immunity (PGE2, TSG6, and STC1).
Article in Stem cells (Dayton, Ohio), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 193 citations in OpenAlex.
- STC1 promotes osteogenic differentiation and represses inflammation via inhibition of NF‑κB signaling in mesenchymal stromal cells.Molecular medicine reports · 2026Article
- Identification of a long-term surviving human mesenchymal stromal cell subpopulation and implications for recessive dystrophic epidermolysis bullosa treatment.Stem cell research & therapy · 2026Article
- An animal component-free bioprocess for synthesizing 3D human matrix scaffolds using mesenchymal stromal cells.Frontiers in cell and developmental biology · 2026Article
- Engineered 3D mesenchymal stem cell aggregates with multifunctional prowess for bone regeneration: Current status and future prospects.Journal of advanced research · 2026Review
- Harnessing mesenchymal stem/stromal cells-based therapies for rheumatoid arthritis: mechanisms, clinical applications, and microenvironmental interactions.Stem cell research & therapy · 2025Review
- Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights.Stem cell research & therapy · 2025Review
- Enhanced immunomodulatory effects of canine adipose tissue-derived mesenchymal stem cells in 3D culture.Frontiers in veterinary science · 2025Article
- Current Status of Research on Nanomaterials Combined with Mesenchymal Stem Cells for the Treatment of Ischemic Stroke.Neuromolecular medicine · 2024Review
- Evaluation of a Novel Mechanical Device for the Production of Microfragmented Adipose Tissue for Veterinary Regenerative Medicine: A Proof-of-Concept.International journal of molecular sciences · 2024Article
- 3D spheroid culture synchronizes heterogeneous MSCs into an immunomodulatory phenotype with enhanced anti-inflammatory effects.iScience · 2024Article
- Therapeutic effect of three-dimensional hanging drop cultured human umbilical cord mesenchymal stem cells on osteoarthritis in rabbits.Stem cell research & therapy · 2024Article
- Article
- 3D hUC-MSC spheroids exhibit superior resistance to autophagy and apoptosis of granulosa cells in POF rat model.Reproduction (Cambridge, England) · 2024Article
- Enhanced potent immunosuppression of intracellular adipose tissue-derived stem cell extract by priming with three-dimensional spheroid formation.Scientific reports · 2024Article
- Mesenchymal Stromal Cells Derived from Canine Adipose Tissue: Evaluation of the Effect of Different Shipping Vehicles Used for Clinical Administration.International journal of molecular sciences · 2024Article
- Adipose-Derived Mesenchymal Stem Cell (MSC) Immortalization by Modulation ofJournal of personalized medicine · 2023Article
- Mesenchymal stem cell licensing: enhancing MSC function as a translational approach for the treatment of tendon injury.American journal of veterinary research · 2023Article
- Comparison of Cost and Potency of Human Mesenchymal Stromal Cell Conditioned Medium Derived from 2- and 3-Dimensional Cultures.Bioengineering (Basel, Switzerland) · 2023Article
- The critical role of apoptosis in mesenchymal stromal cell therapeutics and implications in homeostasis and normal tissue repair.Cellular & molecular immunology · 2023Review
- Three-Dimensional Spheroid Culture of Human Mesenchymal Stem Cells: Offering Therapeutic Advantages and In Vitro Glimpses of the In Vivo State.Stem cells translational medicine · 2023Review
62 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Human mesenchymal stem/precursor cells (MSC) are similar to some other stem/progenitor cells in that they compact into spheres when cultured in hanging drops or on nonadherent surfaces. Assembly of MSC into spheres alters many of their properties, including enhanced secretion of factors that mediate inflammatory and immune responses. Here we demonstrated that MSC spontaneously aggregated into sphere-like structures after injection into a subcutaneous air pouch or the peritoneum of mice. The structures were similar to MSC spheres formed in cultures demonstrated by the increased expression of genes for inflammation-modulating factors TSG6, STC1, and COX2, a key enzyme in production of PGE2. To identify the signaling pathways involved, hanging drop cultures were used to follow the time-dependent changes in the cells as they compacted into spheres. Among the genes upregulated were genes for the stress-activated signaling pathway for IL1α/β, and the contact-dependent signaling pathway for Notch. An inhibitor of caspases reduced the upregulation of IL1A/B expression, and inhibitors of IL1 signaling decreased production of PGE2, TSG6, and STC1. Also, inhibition of IL1A/B expression and secretion of PGE2 negated the anti-inflammatory effects of MSC spheres on stimulated macrophages. Experiments with γ-secretase inhibitors suggested that Notch signaling was also required for production of PGE2 but not TSG6 or STC1. The results indicated that assembly of MSC into spheres triggers caspase-dependent IL1 signaling and the secretion of modulators of inflammation and immunity. Similar aggregation in vivo may account for some of the effects observed with administration of the cells in animal models.
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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.