The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Functional heterogeneity of mesenchymal stem cells: Implications for cell therapy
Abstract
The term mesenchymal stem cell (MSCs) was adopted in the 1990s to describe a population of bone‐marrow‐derived cells that demonstrated the capacity for tri‐lineage differentiation at a clonal level. Research conducted during the ensuing decades has demonstrated that MSCs fulfill many functions in addition to connective tissue progenitors including contributing to the HSC niche and regulating the function of immune effector cells of both the innate and adaptive immune system. Despite these advances, fundamental aspects of MSC biology remain indeterminate. For example, the embryonic origin of MSCs and their niche in vivo remains a highly debated topic. More importantly, the mechanisms that regulate self‐renewal and lineage specification have also been largely unexplored. The later is significant in that MSC population's exhibit considerable donor‐to‐donor and intra‐population heterogeneity but knowledge regarding how different functional attributes of MSCs are specified at the population level is unknown. This poses significant obstacles in research and in efforts to develop clinical manufacturing protocols that reproducibly generate functionally equivalent MSC populations. Herein, I discuss data demonstrating that MSC populations are intrinsically heterogeneous, elaborate on the molecular basis for this heterogeneity, and discuss how heterogeneity impacts clinical manufacturing and the therapeutic potency of MSCs. J. Cell. Biochem. 113: 2806–2812, 2012. © 2012 Wiley Periodicals, Inc.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Epithelial-Mesenchymal Transitions in Development and Disease
Thiery, J. P., Acloque, H., Huang, R. Y. J., & Nieto, M. A. (2009) · Cell · doi:10.1016/j.cell.2009.11.007 · Cited by 9,931
Caplan, A. I. (1991) · Journal of Orthopaedic Research · doi:10.1002/jor.1100090504 · Cited by 6,548
A perivascular origin for mesenchymal stem cells in multiple human organs
Crisan, M., Yap, S., Casteilla, L., Chen, C.-W., Corselli, M., Park, T. S., Andriolo, G., Sun, B., Zheng, B., Zhang, L., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.003 · Cited by 3,991
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
Méndez-Ferrer, S., Michurina, T. V., Ferraro, F., Mazloom, A. R., MacArthur, B. D., Lira, S. A., Scadden, D. T., Ma’ayan, A., Enikolopov, G. N., & Frenette, P. S. (2010) · Nature · doi:10.1038/nature09262 · Cited by 3,374
Sacchetti, B., Funari, A., Michienzi, S., Di Cesare, S., Piersanti, S., Saggio, I., Tagliafico, E., Ferrari, S., Robey, P. G., Riminucci, M., et al. (2007) · Cell · doi:10.1016/j.cell.2007.08.025 · Cited by 2,226
Phinney, D. G., & Prockop, D. J. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0637 · Cited by 1,908
Self-citationPerivascular Niche of Postnatal Mesenchymal Stem Cells in Human Bone Marrow and Dental Pulp
Shi, S., & Gronthos, S. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.4.696 · Cited by 1,478
Muraglia, A., Cancedda, R., & Quarto, R. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.7.1161 · Cited by 1,024
Peister, A., Mellad, J. A., Larson, B. L., Hall, B. M., Gibson, L. F., & Prockop, D. J. (2004) · Blood · doi:10.1182/blood-2003-09-3070 · Cited by 994
DiGirolamo, C. M., Stokes, D., Colter, D., Phinney, D. G., Class, R., & Prockop, D. J. (1999) · British Journal of Haematology · doi:10.1046/j.1365-2141.1999.01715.x · Cited by 879
Self-citationZhou, S., Greenberger, J. S., Epperly, M. W., Goff, J. P., Adler, C., LeBoff, M. S., & Glowacki, J. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00377.x · Cited by 785
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
Kuznetsov, S. A., Krebsbach, P. H., Satomura, K., Kerr, J., Riminucci, M., Benayahu, D., & Robey, P. G. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.9.1335 · Cited by 723
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 1×
“However, while the surface phenotype and transcriptome of peri-vascular cells, pericytes and fibroblasts resemble that of marrow-derived MSCs [Covas et al., 2008, pp. 7–9], the latter generally lack the contractility of pericytes and all four lineages exhibit distinct differences in differentiation…”
BackgroundIsolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies
Quirici, N., Soligo, D., Bossolasco, P., Servida, F., Lumini, C., & Deliliers, G. L. (2002) · Experimental Hematology · doi:10.1016/s0301-472x(02)00812-3 · Cited by 579
Asymmetric cell division: recent developments and their implications for tumour biology
Knoblich, J. A. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3010 · Cited by 578
Phinney, D. G., Kopen, G., Isaacson, R. L., & Prockop, D. J. (1999) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(19990315)72:4<570::aid-jcb12>3.0.co;2-w · Cited by 547
Self-citationNeuroepithelial Cells Supply an Initial Transient Wave of MSC Differentiation
Takashima, Y., Era, T., Nakao, K., Kondo, S., Kasuga, M., Smith, A. G., & Nishikawa, S.-I. (2007) · Cell · doi:10.1016/j.cell.2007.04.028 · Cited by 523
SSEA-4 identifies mesenchymal stem cells from bone marrow
Gang, E. J., Bosnakovski, D., Figueiredo, C. A., Visser, J. W., & Perlingeiro, R. C. R. (2007) · Blood · doi:10.1182/blood-2005-11-010504 · Cited by 509
Muschler, G. F., Boehm, C., & Easley, K. (1997) · The Journal of Bone and Joint Surgery (American Volume) · doi:10.2106/00004623-199711000-00012 · Cited by 507
Donor variation in the growth properties and osteogenic potential of human marrow stromal cells
Phinney, D. G., Kopen, G., Righter, W., Webster, S., Tremain, N., & Prockop, D. J. (1999) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(19991201)75:3<424::aid-jcb8>3.0.co;2-8 · Cited by 500
Self-citationCharacterization of mesenchymal stem cells isolated from murine bone marrow by negative selection
Baddoo, M., Hill, K., Wilkinson, R., Gaupp, D., Hughes, C., Kopen, G. C., & Phinney, D. G. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10594 · Cited by 494
Self-citationDellavalle, A., Maroli, G., Covarello, D., Azzoni, E., Innocenzi, A., Perani, L., Antonini, S., Sambasivan, R., Brunelli, S., Tajbakhsh, S., et al. (2011) · Nature Communications · doi:10.1038/ncomms1508 · Cited by 472
Murine marrow‐derived mesenchymal stem cell: isolation, in vitro expansion, and characterization
Meirelles, L. D. S., & Nardi, N. B. (2003) · British Journal of Haematology · doi:10.1046/j.1365-2141.2003.04669.x · Cited by 460
Harvey, D. M., & Levine, A. J. (1991) · Genes & Development · doi:10.1101/gad.5.12b.2375 · Cited by 453
Clinical trials for stem cell therapies
Trounson, A., Thakar, R. G., Lomax, G., & Gibbons, D. (2011) · BMC Medicine · doi:10.1186/1741-7015-9-52 · Cited by 445
Russell, K. C., Phinney, D. G., Lacey, M. R., Barrilleaux, B. L., Meyertholen, K. E., & O'Connor, K. C. (2010) · Stem Cells · doi:10.1002/stem.312 · Cited by 438
Self-citationMitotic Spindle Orientation in Asymmetric and Symmetric Cell Divisions during Animal Development
Morin, X., & Bellaïche, Y. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.06.012 · Cited by 423
Seeger, F. H., Tonn, T., Krzossok, N., Zeiher, A. M., & Dimmeler, S. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehl509 · Cited by 387
Battula, V. L., Treml, S., Bareiss, P. M., Gieseke, F., Roelofs, H., de Zwart, P., Muller, I., Schewe, B., Skutella, T., Fibbe, W. E., et al. (2009) · Haematologica · doi:10.3324/haematol.13740 · Cited by 349
von Bahr, L., Sundberg, B., Lönnies, L., Sander, B., Karbach, H., Hägglund, H., Ljungman, P., Gustafsson, B., Karlsson, H., Le Blanc, K., et al. (2012) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2011.07.023 · Cited by 318
Lennon, D. P., Haynesworth, S. E., Bruder, S. P., Jaiswal, N., & Caplan, A. I. (1996) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/bf02724045 · Cited by 284
Tremain, N., Korkko, J., Ibberson, D., Kopen, G. C., DiGirolamo, C., & Phinney, D. G. (2001) · STEM CELLS · doi:10.1634/stemcells.19-5-408 · Cited by 270
Self-citationClonal heterogeneity in differentiation potential of immortalized human mesenchymal stem cells
Okamoto, T., Aoyama, T., Nakayama, T., Nakamata, T., Hosaka, T., Nishijo, K., Nakamura, T., Kiyono, T., & Toguchida, J. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00661-7 · Cited by 267
Battula, V. L., Evans, K. W., Hollier, B. G., Shi, Y., Marini, F. C., Ayyanan, A., Wang, R.-Y., Brisken, C., Guerra, R., Andreeff, M., et al. (2010) · Stem Cells · doi:10.1002/stem.467 · Cited by 266
Mesenchymal Stem Cell Preparations—Comparing Apples and Oranges
Wagner, W., & Ho, A. D. (2007) · Stem Cell Reviews · doi:10.1007/s12015-007-9001-1 · Cited by 263
Anjos-Afonso, F., & Bonnet, D. (2007) · Blood · doi:10.1182/blood-2006-06-030551 · Cited by 220
Isenmann, S., Arthur, A., Zannettino, A. C., Turner, J. L., Shi, S., Glackin, C. A., & Gronthos, S. (2009) · Stem Cells · doi:10.1002/stem.181 · Cited by 210
Lee, R. H., Seo, M. J., Pulin, A. A., Gregory, C. A., Ylostalo, J., & Prockop, D. J. (2009) · Blood · doi:10.1182/blood-2007-12-128702 · Cited by 182
OSTEOGENIC PRECURSOR CELLS OF BONE MARROW IN RADIATION CHIMERAS
Friedenstein, A., & Kuralesova, A. I. (1971) · Transplantation · doi:10.1097/00007890-197108000-00001 · Cited by 167
Allogeneic mesenchymal stem cells: Agents of immune modulation
English, K., & Mahon, B. P. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23119 · Cited by 143
Building a consensus regarding the nature and origin of mesenchymal stem cells
Phinney, D. G. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10084 · Cited by 138
Self-citationBoregowda, 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-citationDennis, J. E., & Caplan, A. I. (1996) · Journal of Cellular Physiology · Cited by 92
Lai, W.-T., Krishnappa, V., & Phinney, D. G. (2011) · Stem Cells · doi:10.1002/stem.661 · Cited by 85
Self-citationRussell, K. C., Lacey, M. R., Gilliam, J. K., Tucker, H. A., Phinney, D. G., & O’Connor, K. C. (2011) · Biotechnology and Bioengineering · doi:10.1002/bit.23193 · Cited by 85
Self-citationHuman Bone Marrow Mesenchymal Stem Cells: A Systematic Reappraisal Via the Genostem Experience
Charbord, P., Livne, E., Groß, G., Häupl, T., Neves, N. M., Marie, P. J., Bianco, P., & Jørgensen, C. (2010) · Stem Cell Reviews and Reports · doi:10.1007/s12015-010-9125-6 · Cited by 79
Comparative study of mesenchymal stem cells from C57BL/10 and mdx mice
Li, Y., Zhang, C., Xiong, F., Yu, M.-J., Peng, F.-L., Shang, Y., Zhao, C.-P., Xu, Y.-F., Liu, Z.-S., Zhou, C., et al. (2008) · BMC Cell Biology · doi:10.1186/1471-2121-9-24 · Cited by 38
Rizzo, R., Lanzoni, G., Stignani, M., Campioni, D., Alviano, F., Ricci, F., Tazzari, P. L., Melchiorri, L., Scalinci, S. Z., Cuneo, A., et al. (2010) · Cytotherapy · doi:10.3109/14653249.2010.542460 · Cited by 29
Sengers, B. G., Dawson, J. I., & Oreffo, R. O. C. (2009) · Bone · doi:10.1016/j.bone.2009.10.002 · Cited by 29
The ARF-p53 senescence pathway in mouse and human cells.
Wadhwa, R., Sugihara, T., Taira, K., & Kaul, S. C. (2004) · PubMed · doi:10.14670/hh-19.311 · Cited by 17
Cited by
Biological functions of mesenchymal stem cells and clinical implications
Naji, A., Eitoku, M., Favier, B., Deschaseaux, F., Rouas-Freiss, N., & Suganuma, N. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03125-1 · Cited by 624
Skin tissue engineering: wound healing based on stem-cell-based therapeutic strategies
Nourian Dehkordi, A., Mirahmadi Babaheydari, F., Chehelgerdi, M., & Raeisi Dehkordi, S. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1212-2 · Cited by 533
HEO, J. S., CHOI, Y., KIM, H.-S., & KIM, H. O. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2413 · Cited by 495
Siegel, 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
Metadata
- Authors
- Phinney, D. G.
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2012-07-11
- Volume
- 113
- Issue
- 9
- Pages
- 2806-2812
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W1982323513
- Cited by
- 434
- References
- 52
- FWCI
- 10.41
- Type
- journal article
- Language
- en
- Open access
- closed
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.