Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells
Open accessAbstract
Background: Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another. Results: Differences in the adipogenic, chondrogenic, and osteogenic differentiation capacity of murine MSCs harvested from donor animals of different age and number of passages of these cells were observed. Cells from younger donors adhered to tissue culture polystyrene better and proliferated in greater number than those from older animals. Chondrogenic and osteogenic potential decreased with age for each group, and adipogenic differentiation decreased only in cells from the oldest donors. Significant decreases in differentiation potentials due to passage were observed as well for osteogenesis of BMSCs from the youngest donors and chondrogenesis of the cells from the oldest donors. Conclusion: Both increasing age and the number of passages have lineage dependent effects on BMSC differentiation potential. Furthermore, there is an obvious interplay between donor age and cell passage that in the future must be accounted for when developing cell-based therapies for clinical use.
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Many studies have shown that the number and function of different somatic cell populations declines with age, which diminishes the regenerative potential of tissues and organs.
“Many studies have shown that the number and function of different somatic cell populations declines with age, which diminishes the regenerative potential of tissues and organs.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [356]
The Discussion reports that osteogenic and chondrogenic differentiation potential declined with donor age in the murine bone marrow-derived stem cells studied. But the Background describes conflicting findings across studies, and the Conclusion says tissue regeneration in vivo remains for future study. The paper therefore does not establish a general decline in the number and function of different somatic cell populations or show that this diminishes regeneration across tissues and organs. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThere is limited evidence that loss of stem cell function is a major driver of age-related pathology and shortened lifespan.
“However, there is limited evidence that loss of stem cell function is a major driver of age-related pathology and shortened lifespan.355–358”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [356]
The Discussion (page unavailable) says loss of progenitor-cell differentiation potential could contribute to age-related bone and cartilage diseases, while the Conclusion says the study offers little mechanistic explanation and calls for in vivo research. This is consistent with limited evidence for a causal role in pathology, but the paper does not assess whether stem-cell dysfunction is a major driver of age-related pathology or shortened lifespan. (LLM, conf=0.78)
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Cites
Stöckl, S., Göttl, C., Grifka, J. K., & Grässel, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350089 · Cited by 4,670 · see citing works
Stenderup, K. (2003) · Bone · doi:10.1016/j.bone.2003.07.005 · Cited by 1,207 · see citing works
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 · see citing works
Muraglia, A., Cancedda, R., & Quarto, R. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.7.1161 · Cited by 1,025 · see citing works
Age-Related Osteogenic Potential of Mesenchymal Stromal Stem Cells from Human Vertebral Bone Marrow
D’Ippolito, G., Schiller, P. C., Ricordi, C., Roos, B. A., & Howard, G. A. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.7.1115 · Cited by 906 · see citing works
Aging of mesenchymal stem cell in vitro
Bonab, M. M., Alimoghaddam, K., Talebian, F., Ghaffari, S. H., Ghavamzadeh, A., & Nikbin, B. (2006) · BMC Cell Biology · doi:10.1186/1471-2121-7-14 · Cited by 888 · see citing works
Banfi, A., Muraglia, A., Dozin, B., Mastrogiacomo, M., Cancedda, R., & Quarto, R. (2000) · Experimental Hematology · doi:10.1016/s0301-472x(00)00160-0 · Cited by 730 · see citing works
Stem cells, ageing and the quest for immortality
Rando, T. A. (2006) · Nature · doi:10.1038/nature04958 · Cited by 695 · see citing works
Im, G., Shin, Y., & Lee, K.-B. (2005) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2005.05.005 · Cited by 545 · see citing works
Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2.
Lecka‐Czernik, B., Gubrij, I. B., Moerman, E. J., Kajkenova, O., Lipschitz, D. A., Manolagas, S. C., & Jilka, R. L. (1999) · PubMed · Cited by 464 · see citing works
Liu, T. M., Martina, M., Hutmacher, D. W., Hui, J. H. P., Lee, E. H., & Lim, B. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0394 · Cited by 430 · see citing works
Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPAR?2
Lecka‐Czernik, B., Gubrij, I. B., Moerman, E. J., Kajkenova, O., Lipschitz, D. A., Manolagas, S. C., & Jilka, R. L. (1999) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(19990901)74:3 · Cited by 403 · see citing works
Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Cartilage, and Adipose Tissue
Peng, L., Jia, Z., Yin, X., Zhang, X., Liu, Y., Chen, P., Ma, K., & Zhou, C. (2008) · Stem Cells and Development · doi:10.1089/scd.2007.0217 · Cited by 368 · see citing works
Age-related changes in osteogenic stem cells in mice
Bergman, R., Gazit, D., Kahn, A. J., Gruber, H. E., McDougall, S., & Hahn, T. J. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110504 · Cited by 337 · see citing works
Siddappa, R., Licht, R., van Blitterswijk, C., & de Boer, J. (2007) · Journal of Orthopaedic Research® · doi:10.1002/jor.20402 · Cited by 320 · see citing works
Expansion of mesenchymal stem cells isolated from pediatric and adult donor bone marrow
Mareschi, K., Ferrero, I., Rustichelli, D., Aschero, S., Gammaitoni, L., Aglietta, M., Madon, E., & Fagioli, F. (2005) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20681 · Cited by 319 · see citing works
Phenotypic changes of adult porcine mesenchymal stem cells induced by prolonged passaging in culture
Vacanti, V., Kong, E., Suzuki, G., Sato, K., Canty, J. M., & Lee, T. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20376 · Cited by 282 · see citing works
Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages
Jahoda, C. A. B., Whitehouse, C. J., Reynolds, A. J., & Hole, N. (2003) · Experimental Dermatology · doi:10.1111/j.0906-6705.2003.00161.x · Cited by 267 · see citing works
Stenderup, K., Justesen, J., Eriksen, E. F., Rattan, S. I. S., & Kassem, M. S. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.6.1120 · Cited by 242 · see citing works
Simultaneous Preparation and Quantitation of Proteoglycans by Precipitation with Alcian Blue
Bjornsson, S. (1993) · Analytical Biochemistry · doi:10.1006/abio.1993.1197 · Cited by 239 · see citing works
Age‐related impairment of mesenchymal progenitor cell function
Stolzing, A., & Scutt, A. M. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00213.x · Cited by 219 · see citing works
Mendes, S. C., Tibbe, J. M., Veenhof, M., Bakker, K., Both, S. K., Platenburg, P. P., Öner, F. C., de Bruijn, J. D., & van Blitterswijk, C. (2002) · Tissue Engineering · doi:10.1089/107632702320934010 · Cited by 215 · see citing works
Clonal analysis of nestin– vimentin+ multipotent fibroblasts isolated from human dermis
Chen, F. G., Zhang, W. J., Bi, D., Liu, W., Wei, X. H., Chen, F. F., Zhu, L. Q., Cui, L., & Cao, Y. (2007) · Journal of Cell Science · doi:10.1242/jcs.03478 · Cited by 207 · see citing works
Self-citationJustesen, J., Stenderup, K., Eriksen, E. F., & Kassem, M. S. (2002) · Calcified Tissue International · doi:10.1007/s00223-001-2059-x · Cited by 202 · see citing works
Holtorf, H. L., Jansen, J. A., & Mikos, A. G. (2005) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30251 · Cited by 197 · see citing works
Self-citationScharstuhl, A., Schewe, B., Benz, K., Gaissmaier, C., Bühring, H., & Stoop, R. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0300 · Cited by 196 · see citing works
The role of stem cells in aging
Zant, G. E. V., & Liang, Y. (2003) · Experimental Hematology · doi:10.1016/s0301-472x(03)00088-2 · Cited by 194 · see citing works
Altered expression of C/EBP family members results in decreased adipogenesis with aging
Karagiannides, I., Tchkonia, T., Dobson, D. E., Steppan, C. M., Cummins, P., Chan, G., Salvatori, K., Hadzopoulou‐Cladaras, M., & Kirkland, J. L. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.6.r1772 · Cited by 182 · see citing works
HIGH PASSAGE NUMBER OF STEM CELLS ADVERSELY AFFECTS STEM CELL ACTIVATION AND MYOCARDIAL PROTECTION
Crisostomo, P. R., Wang, M., Wairiuko, G. M., Morrell, E. D., Terrell, A. M., Seshadri, P., Nam, U. H., & Meldrum, D. R. (2006) · Shock · doi:10.1097/01.shk.0000235087.45798.93 · Cited by 182 · see citing works
Wall, M. E., Bernacki, S. H., & Loboa, E. G. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0275 · Cited by 170 · see citing works
The Osteogenic Potential of Adipose-Derived Mesenchymal Cells Is Maintained with Aging
Shi, Y.-Y., Nacamuli, R. P., Salim, A., & Longaker, M. T. (2005) · Plastic & Reconstructive Surgery · doi:10.1097/01.prs.0000185606.03222.a9 · Cited by 139 · see citing works
Osteoblast recruitment from stem cells does not decrease by age at late adulthood
Leskelä, H., Risteli, J., Niskanen, S., Koivunen, J. P., Ivaska, K. K., & Lehenkari, P. P. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.10.095 · Cited by 128 · see citing works
Zhang, H., Fazel, S. S., Tian, H., et al. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00019.2005 · Cited by 125 · see citing works
Effect of Aging on the Pluripotential Capacity of Human CD105+ Mesenchymal Stem Cells
Roura, S., Farré, J., Soler‐Botija, C., Llach, A., Hove‐Madsen, L., Cairó, J. J., Gòdia, F., Juan Cinca, A., & Bayés‐Genís, A. (2006) · European Journal of Heart Failure · doi:10.1016/j.ejheart.2005.11.006 · Cited by 108 · see citing works
Hasegawa, Y., Ogihara, T., Yamada, T., et al. (2007) · Endocrinology · doi:10.1210/en.2006-1351 · Cited by 108 · see citing works
Crisostomo, P. R., Markel, T. A., Wang, M., et al. (2007) · Surgery · doi:10.1016/j.surg.2007.04.013 · Cited by 96 · see citing works
Aging bone and cartilage: cross-cutting issues
Carrington, J. L. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.12.041 · Cited by 95 · see citing works
GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing
Kajikawa, Y., Morihara, T., Watanabe, N., Sakamoto, H., Matsuda, K., Kobayashi, M., Oshima, Y., Yoshida, A., Kawata, M., & Kubo, T. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20876 · Cited by 94 · see citing works
Age-Related Changes in the Frequency of Mesenchymal Stem Cells in the Bone Marrow of Rats
Tokalov, S. V., Grüner, S., Schindler, S., Günter, W. O. L. F., Baumann, M. A., & Abolmaali, N. (2007) · Stem Cells and Development · doi:10.1089/scd.2006.0078 · Cited by 92 · see citing works
Impact of Aging on Rat Bone Marrow-Derived Stem Cell Chondrogenesis
Zheng, H., Martin, J. A., Duwayri, Y. M., Falcon, G., & Buckwalter, J. A. (2007) · The Journals of Gerontology Series A · doi:10.1093/gerona/62.2.136 · Cited by 85 · see citing works
Oshima, Y., Watanabe, N., Matsuda, K., Takai, S., Kawata, M., & Kubo, T. (2005) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.4a6280.2005 · Cited by 83 · see citing works
Tchkonia, T., Pirtskhalava, T., Thomou, T., Cartwright, M. J., Wise, B. L., Karagiannides, I., Shpilman, A., Lash, T. L., Becherer, J. D., & Kirkland, J. L. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00295.2007 · Cited by 81 · see citing works
Osteogenic Potential of Postnatal Skeletal Muscle–Derived Stem Cells Is Influenced by Donor Sex
Corsi, K. A., Pollett, J. B., Phillippi, J. A., Ūsas, A., Li, G., & Huard, J. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070702 · Cited by 80 · see citing works
Bishop‐Bailey, D., & Warner, T. D. (2003) · The FASEB Journal · doi:10.1096/fj.02-1075fje · Cited by 74 · see citing works
Relationships between stem cell exhaustion, tumour suppression and ageing
Ruzankina, Y., & Brown, E. J. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6604029 · Cited by 52 · see citing works
Effect of stem cell turnover rates on protection against cancer and aging
Wodarz, D. (2006) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2006.10.013 · Cited by 49 · see citing works
Human articular chondrocytes immortalized by HPV-16 E6 and E7 genes:
Grigolo, B., Roseti, L., Neri, S., et al. (2002) · Osteoarthritis and Cartilage · doi:10.1053/joca.2002.0836 · Cited by 48 · see citing works
Chen, J., Sotome, S., Wang, J., et al. (2005) · PubMed · Cited by 45 · see citing works
Bellows, C. G., Pei, W., Jia, Y., & Heersche, J. N. M. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00088-5 · Cited by 43 · see citing works
Translational Approaches in Tissue Engineering and Regenerative Medicine
Sözer, S., & Hoffman, R. B. (2008) · Cited by 40 · see citing works
Oshima, Y., Watanabe, N., Matsuda, K., et al. (2004) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2004.06.014 · Cited by 38 · see citing works
Shimko, D. A., Burks, C. A., Dee, K. C., & Nauman, E. A. (2004) · Tissue Engineering · doi:10.1089/ten.2004.10.1386 · Cited by 38 · see citing works
Ageing, differentiation, and gene expression in rat epididymal preadipocytes
Kirkland, J. L., Hollenberg, C. H., & Gillon, W. S. (1993) · Biochemistry and Cell Biology · doi:10.1139/o93-079 · Cited by 30 · see citing works
Torii, I., Morikawa, S., Nakano, A., & Morikawa, K. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10326 · Cited by 25 · see citing works
Iwata, Y., Morihara, T., Tachiiri, H., et al. (2008) · Journal of Shoulder and Elbow Surgery · doi:10.1016/j.jse.2007.07.008 · Cited by 20 · see citing works
Biankin, S. A., Collector, M. I., Biankin, A. V., Brown, L. J., Kleeberger, W., Devereux, W. L., Zahnow, C. A., Baylin, S. B., Watkins, D. N., Sharkis, S. J., et al. (2007) · Pathology · doi:10.1080/00313020701230807 · Cited by 17 · see citing works
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Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
Self-citationChoudhery, M. S., Badowski, M., Muise, A., Pierce, J., & Harris, D. T. (2014) · Journal of Translational Medicine · doi:10.1186/1479-5876-12-8 · Cited by 529 · see citing works
Zaim, M., Karaman, S., Cetin, G., & Isik, S. (2012) · Annals of Hematology · doi:10.1007/s00277-012-1438-x · Cited by 294 · see citing works
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Wilson, A., Shehadeh, L. A., Yu, H., & Webster, K. A. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-229 · Cited by 135 · see citing works
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Shen, J., Tsai, Y.-T., DiMarco, N. M., Long, M. A., Sun, X., & Tang, L. (2011) · Scientific Reports · doi:10.1038/srep00067 · Cited by 117 · see citing works
Wang, H., Chen, Q., Lee, S., Choi, Y., Brad Johnson, F., & Pignolo, R. J. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00838.x · Cited by 81 · see citing works
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Barilani, M., Lovejoy, C., Piras, R., Abramov, A. Y., Lazzari, L., & Angelova, P. R. (2022) · Journal of Cellular Physiology · doi:10.1002/jcp.30638 · Cited by 31 · see citing works
- Authors
- Kretlow, J. D., Jin, Y.-Q., Liu, W., Zhang, W. J., Hong, T.-H., Zhou, G., Baggett, L. S., Mikos, A. G., & Cao, Y.
- Affiliations
- Rice University (US)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Cao, Yilin
- ORCID
- Venue
- BMC Cell Biology
- Published
- 2008-10-28
- Volume
- 9
- Issue
- 1
- Pages
- 60-60
- ISSN
- 1471-2121 (ISSN-L)
- PMC
- PMC2584028
- OpenAlex
- W2039533211
- Cited by
- 466
- References
- 56
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 15 · 2023: 24 · 2022: 18 · 2021: 35 · 2020: 32 · 2019: 27 · 2018: 35 · 2017: 33 · 2016: 32 · 2015: 38 · 2014: 32 · 2013: 37 · 2012: 36
- FWCI
- 7.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Cell Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Rice University
- Ministry of Science and Technology of the People's Republic of China
- Shanghai Jiao Tong University
- National Institutes of Health
- School of Medicine, Shanghai Jiao Tong University
- National Institute of General Medical Sciences (T32GM008362, T32GM007330)
- National Institute of Dental and Craniofacial Research (R01DE015164)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- bone marrow-derived mesenchymal stem cells, donor age, subculture, multilineage differentiation, adipogenesis, chondrogenic differentiation, osteogenic differentiation, cell expansion, cell therapy
- MeSH terms
- Aging, Animals, Bone Marrow Cells, Cell Adhesion, Cell Differentiation, Cells, Cultured, Male, Mice, Transgenic, Osteogenesis, Chondrogenesis, Cell Proliferation, Adipogenesis, Mice, Mesenchymal Stem Cells
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