Concise Review: When Colonies Are Not Clones: Evidence and Implications of Intracolony Heterogeneity in Mesenchymal Stem Cells
- 21 February 2016
- journal article
- review article
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 34 (5), 1135-1141
- https://doi.org/10.1002/stem.2296
Abstract
The emergence of heterogeneity in putative mesenchymal stem cell (MSC) populations during in vitro expansion is not fully appreciated by the various communities who study, engineer, and use such stem cells. However, this functional diversity holds direct implications for basic research and therapeutic applications of MSCs that require predictable phenotypic function and efficacy. Despite numerous clinical trials pursuing MSC therapies, the in vitro expansion of homogeneous populations to therapeutically relevant quantities remains an elusive goal. Variation in MSC cultures has been noted not only among donors and within populations expanded from the same donor, but also debatably within single-cell-derived colonies. The potential for even intracolony heterogeneity suggests that any purified subpopulation will inevitably become heterogeneous upon further expansion under current culture conditions. Here, we review the noted or retrospective evidence of intracolony MSC heterogeneity, to facilitate discussion of its possible causes and potential solutions to its mitigation. This analysis suggests that functional diversity within an MSC colony must be considered in design of experiments and trials for even non-clonal stem cell populations, and can be mitigated or even exploited when the mechanisms of onset are better understood.Keywords
Funding Information
- US National Science Foundation Graduate Research Fellowship (1122374)
This publication has 36 references indexed in Scilit:
- “Mesenchymal” Stem CellsAnnual Review of Cell and Developmental Biology, 2014
- Multivariate biophysical markers predictive of mesenchymal stromal cell multipotencyProceedings of the National Academy of Sciences of the United States of America, 2014
- Onset of heterogeneity in culture-expanded bone marrow stromal cellsStem Cell Research, 2013
- Physical Cues of Biomaterials Guide Stem Cell Differentiation FateChemical Reviews, 2013
- Multipotent mesenchymal stromal cells and the innate immune systemNature Reviews Immunology, 2012
- Mesenchymal Stem Cells for Bone Repair and Metabolic Bone DiseasesMayo Clinic Proceedings, 2009
- Trafficking and differentiation of mesenchymal stem cellsJournal of Cellular Biochemistry, 2009
- Mesenchymal stem cells in health and diseaseNature Reviews Immunology, 2008
- Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statementCytotherapy, 2005
- Mesenchymal stem cellsJournal of Orthopaedic Research, 1991