The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Donor age and long-term culture affect differentiation and proliferation of human bone marrow mesenchymal stem cells
Abstract
Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) represent a promising cell-based therapy for a number of degenerative conditions. Many applications require cell expansion and involve the treatment of diseases and conditions found in an aging population. Therefore, the effects of donor age and long-term passage must be clarified. In this study, the effects of donor age and long-term passage on the morphology, proliferation potential, characteristics, mesodermal differentiation ability, and transdifferentiation potential of hMSCs towards neurogenic lineage were evaluated. Cells from child donors (0-12 years, n = 6) maintained their fibroblast-like morphology up to higher passages and proliferated in a greater number than those from adult (25-50 years, n = 6) and old (over 60 years, n = 6) donors. Adipogenic, osteogenic, and neurogenic differentiation potential decreased with age, while chondrogenic potential did not change. Long-term passage affected the morphology and proliferation of hMSCs from all ages. With increasing passage number, proliferation rate decreased and cells lost their typical morphology. Expression levels of neural markers (β III tubulin and NSE) and topo II isoforms in populations of nondifferentiated hMSCs were investigated by reverse transcription polymerase chain reaction analysis. While neural marker and topo IIβ expression levels increased due to increasing passage number in adult hMSCs compared to child hMSCs, topo IIα decreased in both. These results indicated that, even under highly standardized culture conditions, donor age and long-term passage have effects on hMSC characteristics, which should be taken into account prior to stem cell-based therapies.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“with older donors of BM-MSCs having lower proliferation rates [246], [249] and osteogenic [246], [248], adipogenic and neurogenic [248] capacities.”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [248]
In the citing paper
“In addition, the number of MSC passage [246], [247], [248] and the donor variability [246], [247], [248] cannot be ignored since MSC activity and, thus, the properties of MSC-secretome can be affected by donor age and sex [246], [248], [249]”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [248]
Citations
Cites
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., & Horwitz, E. M. (2006) · Cytotherapy · doi:10.1080/14653240600855905 · Cited by 17,766
Chamberlain, G., Fox, J. M., Ashton, B. A., & Middleton, J. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0197 · Cited by 2,432
Immunomodulatory properties of mesenchymal stromal cells
Nauta, A. J., & Fibbe, W. E. (2007) · Blood · doi:10.1182/blood-2007-02-069716 · Cited by 1,808
Adult Bone Marrow Stromal Cells Differentiate into Neural Cells in Vitro
Sanchez‐Ramos, J., Song, S., Cardozo‐Pelaez, F., Hazzi, C., Stedeford, T. J., Willing, A. E., Freeman, T. B., Saporta, S., Janssen, W. E., Patel, N. A., et al. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7389 · Cited by 1,568
Chondrogenic Differentiation of Cultured Human Mesenchymal Stem Cells from Marrow
Mackay, A. M., Beck, S. C., Murphy, M. J., Barry, F., Chichester, C. O., & Pittenger, M. F. (1998) · Tissue Engineering · doi:10.1089/ten.1998.4.415 · Cited by 1,302
Stenderup, K. (2003) · Bone · doi:10.1016/j.bone.2003.07.005 · Cited by 1,207
Stolzing, A., Jones, E., McGonagle, D., & Scutt, A. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.12.002 · Cited by 1,195
Replicative Senescence of Mesenchymal Stem Cells: A Continuous and Organized Process
Wagner, W., Horn, P., Castoldi, M., Diehlmann, A., Bork, S., Saffrich, R., Beneš, V., Blake, J., Pfister, S. M., Eckstein, V., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002213 · Cited by 1,152
Why are MSCs therapeutic? New data: new insight
Caplan, A. I. (2008) · The Journal of Pathology · doi:10.1002/path.2469 · Cited by 1,115
Cited by
Sorted by citations
Zhang, J., Guan, J., Niu, X., Hu, G., Guo, S., Li, Q., Xie, Z., Zhang, C., & Wang, Y. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0417-0 · Cited by 804
“Moreover, the proliferation and differentiation potential of MSCs declines significantly when age-related disorders occur and with increasing age [4,5].”
BackgroundJin, H. J., Bae, Y., Kim, M., Kwon, S., Jeon, H., Choi, S. Y., Kim, S. M., Yang, Y., Oh, W., & Chang, J. H. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140917986 · Cited by 664
“[31].”
Spinal Fusion in the Next Generation: Gene and Cell Therapy Approaches
Barba, M., Cicione, C., Bernardini, C., Campana, V., Pagano, E., Michetti, F., Logroscino, G., & Lattanzi, W. (2014) · The Scientific World JOURNAL · doi:10.1155/2014/406159 · Cited by 514
“However, both sources are subjected to a significant decline in stem cell number and proliferative capacities in elderly, when main indications for regenerative medicine approaches are encountered [38].”
BackgroundHu, G., Li, Q., Niu, X., Hu, B., Liu, J., Zhou, S.-M., Guo, S., Lang, H., Zhang, C., Wang, Y., et al. (2015) · Stem Cell Research & Therapy · doi:10.1186/scrt546 · Cited by 400
“In addition, only a limited number of BMSCs can be obtained initially from a single donor, limiting their further application [11,12].”
BackgroundEffects of Oxidative Stress on Mesenchymal Stem Cell Biology
Denu, R. A., & Hematti, P. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/2989076 · Cited by 338
“, CD13, CD29, and CD44), and the ability to suppress T cell proliferation diminishes [41, 82, 83].”
Background
Metadata
- Authors
- Zaim, M., Karaman, S., Cetin, G., & Isik, S.
- Affiliations
- Fatih University (TR)
- Şişli Etfal Eğitim ve Araştırma Hastanesi (TR)
- Venue
- Annals of Hematology
- Published
- 2012-03-08
- Volume
- 91
- Issue
- 8
- Pages
- 1175-1186
- ISSN
- 0939-5555 (ISSN-L)
- 1432-0584
- OpenAlex
- W1978468353
- Cited by
- 294
- References
- 41
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 15 · 2023: 24 · 2022: 19 · 2021: 35 · 2020: 27 · 2019: 23 · 2018: 19 · 2017: 28 · 2016: 23 · 2015: 18 · 2014: 24 · 2013: 12 · 2012: 4
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Annals of Hematology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
- mesenchymal stem cells, bone marrow, donor age, cellular aging, cell proliferation, multilineage differentiation, neurogenic differentiation, transdifferentiation, topoisomerase II, neural markers, stem cell therapy
- MeSH terms
- Adult, Age Factors, Aged, Aging, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Time Factors, Tissue Donors, Cell Proliferation, Mesenchymal Stem Cells, Primary Cell Culture
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 ›
Are you an author, or do you see a problem with this page? Request a review