Spheroid Culture of Mesenchymal Stem Cells
Open accessAbstract
Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs) cultured in spheroids have enhanced anti‐inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids. Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses. In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown.
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Spheroid cell culture has been developed for research on cancer, stem cells, and many organs, including liver, kidney, and heart.
“This approach has been developed in the research of cancer (7, 76, 102), stem cells (17, 120), and many organs (such as liver, kidney, heart, etc.) (3,16,64,75).”
From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [17]
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Self-citation
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Sheikhi, K., Ghaderi, S., Firouzi, H., Rahimibarghani, S., Shabani, E., Afkhami, H., & Yarahmadi, A. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1517369 · Cited by 20 · see citing works
- Authors
- Cesarz, Z., & Tamama, K.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Tamama, Kenichi
- Venue
- Stem Cells International
- Publisher
- Wiley
- Published
- 2015-11-16
- Volume
- 2016
- Issue
- 1
- Pages
- 9176357-9176357
- ISSN
- 1687-966X (ISSN-L)
- 1687-9678
- PMC
- PMC4663368
- OpenAlex
- W1603093856
- Cited by
- 475
- References
- 141
- Citations by year
- 2026: 22 · 2025: 32 · 2024: 46 · 2023: 51 · 2022: 53 · 2021: 85 · 2020: 55 · 2019: 37 · 2018: 45 · 2017: 38 · 2016: 10 · 2015: 1
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cells International (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Pittsburgh
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- mesenchymal stem cells, spheroid culture, 3D cell aggregates, stemness, stem cell markers, replicative senescence, gene expression profiling, cell morphology, angiogenesis, tissue regeneration, cell transplantation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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