Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells
Open accessAbstract
Background: Mesenchymal stromal cells (MSCs) are attractive for cell-based therapies ranging from regenerative medicine and tissue engineering to immunomodulation. However, clinical efficacy is variable and it is unclear how the phenotypes defining bone marrow (BM)-derived MSCs as well as donor characteristics affect their functional properties. Methods: BM-MSCs were isolated from 53 (25 female, 28 male; age: 13 to 80 years) donors and analyzed by: (1) phenotype using flow cytometry and cell size measurement; (2) in vitro growth kinetics using population doubling time; (3) colony formation capacity and telomerase activity; and (4) function by in vitro differentiation capacity, suppression of T cell proliferation, cytokines and trophic factors secretion, and hormone and growth factor receptor expression. Additionally, expression of Oct4 , Nanog , Prdm14 and SOX2 mRNA was compared to pluripotent stem cells. Results: BM-MSCs from younger donors showed increased expression of MCAM, VCAM-1, ALCAM, PDGFRβ, PDL-1, Thy1 and CD71, and led to lower IL-6 production when co-cultured with activated T cells. Female BM-MSCs showed increased expression of IFN-γR1 and IL-6β, and were more potent in T cell proliferation suppression. High-clonogenic BM-MSCs were smaller, divided more rapidly and were more frequent in BM-MSC preparations from younger female donors. CD10, β1integrin, HCAM, CD71, VCAM-1, IFN-γR1, MCAM, ALCAM, LNGFR and HLA ABC were correlated to BM-MSC preparations with high clonogenic potential and expression of IFN-γR1, MCAM and HLA ABC was associated with rapid growth of BM-MSCs. The mesodermal differentiation capacity of BM-MSCs was unaffected by donor age or gender but was affected by phenotype (CD10, IFN-γR1, GD2). BM-MSCs from female and male donors expressed androgen receptor and FGFR3, and secreted VEGF-A, HGF, LIF, Angiopoietin-1, basic fibroblast growth factor (bFGF) and NGFB. HGF secretion correlated negatively to the expression of CD71, CD140b and Galectin 1. The expression of Oct4, Nanog and Prdm14 mRNA in BM-MSCs was much lower compared to pluripotent stem cells and was not related to donor age or gender. Prdm14 mRNA expression correlated positively to the clonogenic potential of BM-MSCs . Conclusions: By identifying donor-related effects and assigning phenotypes of BM-MSC preparations to functional properties, we provide useful tools for assay development and production for clinical applications of BM-MSC preparations.
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BMSCs from older adults secrete more IL-6 than those from younger adults.
“One study found more IL-6 from BMSCs from older adults than younger adults”
From Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature (2024) · cites this paper as [83]
The Results section (Figure 5C) reports more IL-6 in the supernatant of BM-MSCs from older donors than younger donors, but only when the cells were co-cultured with activated allogeneic T cells. The citing sentence omits that experimental condition and reads as a general claim about IL-6 secretion. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBMSCs can regulate osteoblast and osteoclast activity through secretion of SASP.
“BMSCs can regulate osteoblast and osteoclast activity through the secretion of SASP [83].”
From Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature (2024) · cites this paper as [83]
The Results section on trophic-factor secretion reports that BM-MSCs secrete several factors, including VEGF-A and HGF. But the paper does not identify those secretions as SASP or show that they regulate osteoblast and osteoclast activity; searches for SASP and for osteoblast/osteoclast activity found no such passage. Page numbers were not available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredPhenotype, donor age, and sex significantly affect the function of human bone marrow-derived MSCs.
“Siegel et al. (2013) showed that phenotype, donor age, and sex significantly affect the function of human bone marrow-derived MSCs.”
From Primary cell cultures versus immortalized cell lines: critical comparative insights into biological fidelity and translational applications (2026) · cites this paper as Siegel et al. (2013)
In human bone marrow-derived MSC preparations, younger donors (<45 years) had higher colony-forming efficiency compared to older donors (>65 years).
“Their study of 50 MSC preparations demonstrated that younger donors (<45 years) had higher colony-forming efficiency compared to older donors (>65 years), and female donors exhibited greater colony-forming frequencies than male donors, highlighting the impact of donor characteristics on reproducibility and functional uniformity.”
From Primary cell cultures versus immortalized cell lines: critical comparative insights into biological fidelity and translational applications (2026) · cites this paper as Siegel et al. (2013)
In human bone marrow-derived MSC preparations, female donors exhibited greater colony-forming frequencies than male donors.
“Their study of 50 MSC preparations demonstrated that younger donors (<45 years) had higher colony-forming efficiency compared to older donors (>65 years), and female donors exhibited greater colony-forming frequencies than male donors, highlighting the impact of donor characteristics on reproducibility and functional uniformity.”
From Primary cell cultures versus immortalized cell lines: critical comparative insights into biological fidelity and translational applications (2026) · cites this paper as Siegel et al. (2013)
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The Pros and Cons of Mesenchymal Stem Cell-Based Therapies
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Adipose-derived and bone marrow mesenchymal stem cells: A donor-matched comparison
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Effects of Oxidative Stress on Mesenchymal Stem Cell Biology
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A Brief Overview of Global Trends in MSC-Based Cell Therapy
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Characterization of bone marrow-derived mesenchymal stem cells in aging
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Age-related Changes in Bone Marrow Mesenchymal Stromal Cells
Ganguly, P., El‐Jawhari, J. J., Giannoudis, P. V., Burska, A. N., Ponchel, F., & Jones, E. (2017) · Cell Transplantation · doi:10.1177/0963689717721201 · Cited by 226 · see citing works
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Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes
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Self-citationBioprocessing of Mesenchymal Stem Cells and Their Derivatives: Toward Cell-Free Therapeutics
Phelps, J., Sanati‐Nezhad, A., Ungrin, M., Duncan, N. A., & Sen, A. (2018) · Stem Cells International · doi:10.1155/2018/9415367 · Cited by 181 · see citing works
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Mesenchymal stromal cells in renal transplantation: opportunities and challenges
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Microenvironmental contributions to hematopoietic stem cell aging
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The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy
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Current Strategies to Enhance Adipose Stem Cell Function: An Update
Seo, Y., Shin, T., & Kim, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153827 · Cited by 149 · see citing works
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Molecular signatures of mesenchymal stem cell-derived extracellular vesicle-mediated tissue repair
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Mesenchymal Stromal Cells for the Treatment of Graft Versus Host Disease
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Perinatal tissues and cells in tissue engineering and regenerative medicine
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Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro
Bussche, L., Harman, R. M., Syracuse, B., Plante, É., Lu, Y., Curtis, T. M., Ma, M., & de Walle, G. R. V. (2015) · Stem Cell Research & Therapy · doi:10.1186/s13287-015-0037-x · Cited by 82 · see citing works
Cell culture‐derived extracellular vesicles: Considerations for reporting cell culturing parameters
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Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases
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Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches
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Biological Therapies in Regenerative Sports Medicine
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Myelodysplasia is in the niche: novel concepts and emerging therapies
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Autologous Stem Cell Therapy: How Aging and Chronic Diseases Affect Stem and Progenitor Cells
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Biological Considerations in Scaling Up Therapeutic Cell Manufacturing
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Human cardiac extracellular matrix supports myocardial lineage commitment of pluripotent stem cells†
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External factors influencing mesenchymal stem cell fate in vitro
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Recent Advances and Future of Gene Therapy for Bone Regeneration
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Recent Developments in Cellular Immunotherapy for HSCT-Associated Complications
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- Authors
- Siegel, G., Kluba, T., Hermanutz-Klein, U., Bieback, K., Northoff, H., & Schäfer, R.
- Affiliations
- Universitätsklinikum Tübingen (DE)
- Heidelberg University (DE)
- Corresponding author
- Schäfer, Richard
- Venue
- BMC Medicine
- Published
- 2013-06-11
- Volume
- 11
- Issue
- 1
- Pages
- 146-146
- ISSN
- 1741-7015 (ISSN-L)
- PMC
- PMC3694028
- OpenAlex
- W2043060398
- Cited by
- 493
- References
- 80
- Citations by year
- 2026: 19 · 2025: 32 · 2024: 42 · 2023: 33 · 2022: 33 · 2021: 69 · 2020: 51 · 2019: 49 · 2018: 28 · 2017: 30 · 2016: 44 · 2015: 32 · 2014: 26 · 2013: 4
- FWCI
- 17.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Eberhard Karls Universität Tübingen
- Harvard Stem Cell Institute
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- bone marrow-derived mesenchymal stromal cells, donor age, donor gender, cell phenotype, clonogenicity, T cell proliferation inhibition, immunomodulation, mesoderm differentiation, IFN-gamma receptor 1, hepatocyte growth factor, Oct4, Nanog, pluripotency genes, cell therapy
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Cell Differentiation, Cells, Cultured, Female, Humans, Male, Middle Aged, Sex Factors, Immunophenotyping, Living Donors, Young Adult, Mesenchymal Stem Cells
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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