PMID- 30943212
OWN - NLM
STAT- MEDLINE
DCOM- 20191231
LR  - 20200309
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 14
IP  - 4
DP  - 2019
TI  - Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell 
      time lapsed analysis.
PG  - e0213452
LID - 10.1371/journal.pone.0213452 [doi]
LID - e0213452
AB  - 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.
FAU - Rennerfeldt, Deena A
AU  - Rennerfeldt DA
AD  - Department of Biological Engineering, Massachusetts Institute of Technology, 
      Cambridge, Massachusetts, United States of America.
FAU - Raminhos, Joana S
AU  - Raminhos JS
AUID- ORCID: 0000-0001-9658-9283
AD  - Department of Materials Science, Faculty of Science and Technology, New 
      University of Lisbon, Caparica, Portugal.
FAU - Leff, Samantha M
AU  - Leff SM
AD  - Department of Biological Engineering, Massachusetts Institute of Technology, 
      Cambridge, Massachusetts, United States of America.
FAU - Manning, Pristinavae
AU  - Manning P
AD  - Department of Biological Engineering, Massachusetts Institute of Technology, 
      Cambridge, Massachusetts, United States of America.
FAU - Van Vliet, Krystyn J
AU  - Van Vliet KJ
AUID- ORCID: 0000-0001-5735-0560
AD  - Department of Biological Engineering, Massachusetts Institute of Technology, 
      Cambridge, Massachusetts, United States of America.
AD  - Department of Materials Science and Engineering, Massachusetts Institute of 
      Technology, Cambridge, Massachusetts, United States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Video-Audio Media
DEP - 20190403
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Bone Marrow Cells/*physiology
MH  - Cell Division/*physiology
MH  - Cells, Cultured
MH  - Colony-Forming Units Assay
MH  - Humans
MH  - *Intravital Microscopy
MH  - Mesenchymal Stem Cells/*physiology
MH  - Single-Cell Analysis
MH  - Time-Lapse Imaging
PMC - PMC6447157
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/04/04 06:00
MHDA- 2020/01/01 06:00
PMCR- 2019/04/03
CRDT- 2019/04/04 06:00
PHST- 2018/09/21 00:00 [received]
PHST- 2019/02/21 00:00 [accepted]
PHST- 2019/04/04 06:00 [entrez]
PHST- 2019/04/04 06:00 [pubmed]
PHST- 2020/01/01 06:00 [medline]
PHST- 2019/04/03 00:00 [pmc-release]
AID - PONE-D-18-27611 [pii]
AID - 10.1371/journal.pone.0213452 [doi]
PST - epublish
SO  - PLoS One. 2019 Apr 3;14(4):e0213452. doi: 10.1371/journal.pone.0213452. 
      eCollection 2019.