The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
In Vitro High-Capacity Assay to Quantify the Clonal Heterogeneity in Trilineage Potential of Mesenchymal Stem Cells Reveals a Complex Hierarchy of Lineage Commitment
Abstract
In regenerative medicine, bone marrow is a promising source of mesenchymal stem cells (MSCs) for a broad range of cellular therapies. This research addresses a basic prerequisite to realize the therapeutic potential of MSCs by developing a novel high-capacity assay to quantify the clonal heterogeneity in potency that is inherent to MSC preparations. The assay utilizes a 96-well format to (1) classify MSCs according to colony-forming efficiency as a measure of proliferation capacity and trilineage potential to exhibit adipo-, chondro-, and osteogenesis as a measure of multipotency and (2) preserve a frozen template of MSC clones of known potency for future use. The heterogeneity in trilineage potential of normal bone marrow MSCs is more complex than previously reported: all eight possible categories of trilineage potential were detected. In this study, the average colony-forming efficiency of MSC preparations was 55–62%, and tripotent MSCs accounted for nearly 50% of the colony-forming cells. The multiple phenotypes detected in this study infer a more convoluted hierarchy of lineage commitment than described in the literature. Greater cell amplification, colony-forming efficiency, and colony diameter for tri- versus unipotent clones suggest that MSC proliferation may be a function of potency. CD146 may be a marker of multipotency, with ∼2-fold difference in mean fluorescence intensity between tri- and unipotent clones. The significance of these findings is discussed in the context of the efficacy of MSC therapies. The in vitro assay described herein will likely have numerous applications given the importance of heterogeneity to the therapeutic potential of MSCs.
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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
Covas, D. T., Panepucci, R. A., Fontes, A. M., Silva, W. A., Orellana, M. D., Freitas, M. C. C., Neder, L., Santos, A. R. D., Peres, L. C., Jamur, M. C., et al. (2008) · Experimental Hematology · doi:10.1016/j.exphem.2007.12.015 · Cited by 610
Cited by
Viswanathan, S., Shi, Y., Galipeau, J., Krampera, M., Leblanc, K., Martin, I., Nolta, J., Phinney, D. G., & Sensebe, L. (2019) · Cytotherapy · doi:10.1016/j.jcyt.2019.08.002 · Cited by 839
Self-citationSiegel, G., Kluba, T., Hermanutz-Klein, U., Bieback, K., Northoff, H., & Schäfer, R. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-146 · Cited by 493
The Origins of Mesenchymal Stromal Cell Heterogeneity
Pevsner-Fischer, M., Levin, S., & Zipori, D. (2011) · Stem Cell Reviews and Reports · doi:10.1007/s12015-011-9229-7 · Cited by 251
Espagnolle, N., Guilloton, F., Deschaseaux, F., Gadelorge, M., Sensébé, L., & Bourin, P. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12168 · Cited by 154
Kuci, Z., Bonig, H., Kreyenberg, H., Bunos, M., Jauch, A., Janssen, J. W. G., kifi, M., Michel, K., Eising, B., Lucchini, G., et al. (2016) · Haematologica · doi:10.3324/haematol.2015.140368 · Cited by 118
Boregowda, S. V., Krishnappa, V., Chambers, J. W., Lograsso, P. V., Lai, W., Ortiz, L. A., & Phinney, D. G. (2012) · STEM CELLS · doi:10.1002/stem.1069 · Cited by 114
Self-citationRussell, K. C., Tucker, H. A., Bunnell, B. A., Andreeff, M., Schober, W., Gaynor, A. S., Strickler, K. L., Lin, S., Lacey, M. R., & O'Connor, K. C. (2013) · Tissue Engineering Part A · doi:10.1089/ten.tea.2012.0649 · Cited by 56
Self-citationConese, M., Piro, D., Carbone, A., Castellani, S., & Di Gioia, S. (2014) · The Scientific World Journal · doi:10.1155/2014/859817 · Cited by 28
Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products
Childs, P. G., Reid, S., Salmeron-Sanchez, M., & Dalby, M. J. (2020) · Biochemical Journal · doi:10.1042/bcj20190382 · Cited by 27
Production and quality testing of multipotent mesenchymal stromal cell therapeutics for clinical use
Bieback, K., Kuçi, S., & Schäfer, R. (2019) · Transfusion · doi:10.1111/trf.15252 · Cited by 24
Wang, L., Yi, W., Ma, L., Lecea, E., Hazlehurst, L. A., Adjeroh, D. A., & Hu, G. (2023) · Cancers · doi:10.3390/cancers15215148 · Cited by 17
TWIST1 and TSG6 are coordinately regulated and function as potency biomarkers in human MSCs
Lee, R. H., Boregowda, S. V., Shigemoto-Kuroda, T., Bae, E., Haga, C. L., Abbery, C. A., Bayless, K. J., Haskell, A., Gregory, C. A., Ortiz, L. A., et al. (2023) · Science Advances · doi:10.1126/sciadv.adi2387 · Cited by 16
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Metadata
- Authors
- Russell, K. C., Phinney, D. G., Lacey, M. R., Barrilleaux, B. L., Meyertholen, K. E., & O'Connor, K. C.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-02-01
- Volume
- 28
- Issue
- 4
- Pages
- 788-798
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W1979155684
- Cited by
- 438
- References
- 3
- FWCI
- 14.77
- Type
- journal article
- Language
- en
- Open access
- closed
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