PMID- 28406754
OWN - NLM
STAT- MEDLINE
DCOM- 20170724
LR  - 20181202
IS  - 1937-3392 (Electronic)
IS  - 1937-3384 (Print)
IS  - 1937-3384 (Linking)
VI  - 23
IP  - 4
DP  - 2017 Apr
TI  - Spheroid Coculture of Hematopoietic Stem/Progenitor Cells and Monolayer Expanded 
      Mesenchymal Stem/Stromal Cells in Polydimethylsiloxane Microwells Modestly 
      Improves In Vitro Hematopoietic Stem/Progenitor Cell Expansion.
PG  - 200-218
LID - 10.1089/ten.tec.2016.0329 [doi]
AB  - While two-dimensional (2D) monolayers of mesenchymal stem/stromal cells (MSCs) 
      have been shown to enhance hematopoietic stem/progenitor cell (HSPC) expansion in 
      vitro, expanded cells do not engraft long term in human recipients. This outcome 
      is attributed to the failure of 2D culture to recapitulate the bone marrow (BM) 
      niche signal milieu. Herein, we evaluated the capacity of a novel 
      three-dimensional (3D) coculture system to support HSPC expansion in vitro. A 
      high-throughput polydimethylsiloxane (PDMS) microwell platform was used to 
      manufacture thousands of uniform 3D multicellular coculture spheroids. Relative 
      gene expression in 3D spheroid versus 2D adherent BM-derived MSC cultures was 
      characterized and compared with literature reports. We evaluated coculture 
      spheroids, each containing 25-400 MSCs and 10 umbilical cord blood (CB)-derived 
      CD34(+) progenitor cells. At low exogenous cytokine concentrations, 2D and 3D MSC 
      coculture modestly improved overall hematopoietic cell and CD34(+) cell expansion 
      outcomes. By contrast, a substantial increase in CD34(+)CD38(-) cell yield was 
      observed in PDMS microwell cultures, regardless of the presence or absence of 
      MSCs. This outcome indicated that CD34(+)CD38(-) cell culture yield could be 
      increased using the microwell platform alone, even without MSC coculture support. 
      We found that the increase in CD34(+)CD38(-) cell yield observed in PDMS 
      microwell cultures did not translate to enhanced engraftment in NOD/SCID gamma 
      (NSG) mice or a modification in the relative human hematopoietic lineages 
      established in engrafted mice. In summary, there was no statistical difference in 
      CD34(+) cell yield from 2D or 3D cocultures, and MSC coculture support provided 
      only modest benefit in either geometry. While the high-throughput 3D microwell 
      platform may provide a useful model system for studying cells in coculture, 
      further optimization will be required to generate HSPC yields suitable for use in 
      clinical applications.
FAU - Futrega, Kathryn
AU  - Futrega K
AD  - 1 Stem Cell Therapies Laboratory, Translational Research Institute, Queensland 
      University of Technology , Brisbane, Australia .
FAU - Atkinson, Kerry
AU  - Atkinson K
AD  - 1 Stem Cell Therapies Laboratory, Translational Research Institute, Queensland 
      University of Technology , Brisbane, Australia .
FAU - Lott, William B
AU  - Lott WB
AD  - 1 Stem Cell Therapies Laboratory, Translational Research Institute, Queensland 
      University of Technology , Brisbane, Australia .
FAU - Doran, Michael R
AU  - Doran MR
AD  - 1 Stem Cell Therapies Laboratory, Translational Research Institute, Queensland 
      University of Technology , Brisbane, Australia .
AD  - 2 Mater Research Institute - University of Queensland, Translational Research 
      Institute , Brisbane, Australia .
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tissue Eng Part C Methods
JT  - Tissue engineering. Part C, Methods
JID - 101466663
RN  - 0 (Dimethylpolysiloxanes)
RN  - 63148-62-9 (baysilon)
SB  - IM
MH  - Animals
MH  - *Cell Proliferation
MH  - Coculture Techniques/methods
MH  - Dimethylpolysiloxanes/*chemistry
MH  - Graft Survival
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/cytology/*metabolism
MH  - Heterografts
MH  - Humans
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Spheroids, Cellular/cytology/*metabolism
PMC - PMC5397247
OTO - NOTNLM
OT  - co-culture
OT  - cord blood hematopoietic stem cells
OT  - engraftment
OT  - mesenchymal stem cells
OT  - microwell
OT  - spheroid culture
COIS- No competing financial interests exist.
EDAT- 2017/04/14 06:00
MHDA- 2017/07/25 06:00
PMCR- 2017/04/01
CRDT- 2017/04/14 06:00
PHST- 2017/04/14 06:00 [entrez]
PHST- 2017/04/14 06:00 [pubmed]
PHST- 2017/07/25 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - 10.1089/ten.tec.2016.0329 [pii]
AID - 10.1089/ten.tec.2016.0329 [doi]
PST - ppublish
SO  - Tissue Eng Part C Methods. 2017 Apr;23(4):200-218. doi: 
      10.1089/ten.tec.2016.0329.