Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis

Bone marrow stromal cells (BMSCs) include a subset of stem cells that are considered promising for developmental studies and therapeutic applications. While it is appreciated generally that BMSC populations can exhibit morphological and functional heterogeneity upon in vitro culture expansion, the p...

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Bibliographic Details
Published in:PloS one 2019-04, Vol.14 (4), p.e0213452-e0213452
Main Authors: Rennerfeldt, Deena A, Raminhos, Joana S, Leff, Samantha M, Manning, Pristinavae, Van Vliet, Krystyn J
Format: Article
Language:English
Subjects:
Bioengineering
Biology and Life Sciences
Bone marrow
Bone Marrow Cells - physiology
Care and treatment
Cell culture
Cell Division - physiology
Cells, Cultured
Clinical trials
Colonies
Colony-Forming Units Assay
Engineering
Health aspects
Heterogeneity
Humans
Intravital Microscopy
Materials science
Mesenchymal stem cells
Mesenchymal Stem Cells - physiology
Mesenchyme
Methods
Parkinson disease
Physical Sciences
Research and Analysis Methods
Senescence
Single-Cell Analysis
Stem cell research
Stem cell transplantation
Stem cells
Stromal cells
Subpopulations
Therapeutic applications
Time-Lapse Imaging
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Summary:Bone marrow stromal cells (BMSCs) include a subset of stem cells that are considered promising for developmental studies and therapeutic applications. While it is appreciated generally that BMSC populations can exhibit morphological and functional heterogeneity upon in vitro culture expansion, the potential for heterogeneity within a single colony forming unit-generated ostensibly from a single mother cell-is less explored but is critical to design of both fundamental studies and cell therapy production. Here we observed BMSC colony formation in real time via time lapsed optical imaging and analysis, to quantify whether and how heterogeneity emerged over multiple cell divisions spanning the duration of a typical colony formation unit assay. These analyses demonstrate that such colonies are neither homogeneous subpopulations of stem cells nor necessarily derived from single originating cells. While the mechanisms for and causes of this intracolony heterogeneity are not understood fully, we further demonstrate that extensive cell-cell contacts do not correlate with senescence, but that media exchange was concurrent with diversification in even the most uniform single-cell-derived colonies. These direct quantitative observations and visualizations of colony formation provide new insights that are motivated by significant implications for both basic research and stem cell-based therapies.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0213452