PMID- 22971005
OWN - NLM
STAT- MEDLINE
DCOM- 20130709
LR  - 20211021
IS  - 1937-335X (Electronic)
IS  - 1937-3341 (Print)
IS  - 1937-3341 (Linking)
VI  - 19
IP  - 1-2
DP  - 2013 Jan
TI  - Dissecting the role of human embryonic stem cell-derived mesenchymal cells in 
      human umbilical vein endothelial cell network stabilization in three-dimensional 
      environments.
PG  - 211-23
LID - 10.1089/ten.tea.2011.0408 [doi]
AB  - The microvasculature is principally composed of two cell types: endothelium and 
      mural support cells. Multiple sources are available for human endothelial cells 
      (ECs) but sources for human microvascular mural cells (MCs) are limited. We 
      derived multipotent mesenchymal progenitor cells from human embryonic stem cells 
      (hES-MC) that can function as an MC and stabilize human EC networks in 
      three-dimensional (3D) collagen-fibronectin culture by paracrine mechanisms. 
      Here, we have investigated the basis for hES-MC-mediated stabilization and 
      identified the pleiotropic growth factor hepatocyte growth factor/scatter factor 
      (HGF/SF) as a putative hES-MC-derived regulator of EC network stabilization in 3D 
      in vitro culture. Pharmacological inhibition of the HGF receptor (Met) (1 mum 
      SU11274) inhibits EC network formation in the presence of hES-MC. hES-MC produce 
      and release HGF while human umbilical vein endothelial cells (HUVEC) do not. When 
      HUVEC are cultured alone the networks collapse, but in the presence of 
      recombinant human HGF or conditioned media from human HGF-transduced cells 
      significantly more networks persist. In addition, HUVEC transduced to 
      constitutively express human HGF also form stable networks by autocrine 
      mechanisms. By enzyme-linked immunosorbent assay, the coculture media were 
      enriched in both angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2), but at 
      significantly different levels (Ang1=159+/-15 pg/mL vs. Ang2=30,867+/-2685 pg/mL) 
      contributed by hES-MC and HUVEC, respectively. Although the coculture cells 
      formed stabile network architectures, their morphology suggests the assembly of 
      an immature plexus. When HUVEC and hES-MC were implanted subcutaneously in immune 
      compromised Rag1 mice, hES-MC increased their contact with HUVEC along the axis 
      of the vessel. This data suggests that HUVEC and hES-MC form an immature plexus 
      mediated in part by HGF and angiopoietins that is capable of maturation under the 
      correct environmental conditions (e.g., in vivo). Therefore, hES-MC can function 
      as microvascular MCs and may be a useful cell source for testing EC-MC 
      interactions.
FAU - Boyd, Nolan L
AU  - Boyd NL
AD  - Cardiovascular Innovation Institute, University of Louisville, Louisville, 
      Kentucky, USA. nolan.boyd@louisville.edu
FAU - Nunes, Sara S
AU  - Nunes SS
FAU - Krishnan, Laxminarayanan
AU  - Krishnan L
FAU - Jokinen, Jenny D
AU  - Jokinen JD
FAU - Ramakrishnan, Venkat M
AU  - Ramakrishnan VM
FAU - Bugg, Amy R
AU  - Bugg AR
FAU - Hoying, James B
AU  - Hoying JB
LA  - eng
GR  - EB007556/EB/NIBIB NIH HHS/United States
GR  - P20 RR016481/RR/NCRR NIH HHS/United States
GR  - P20RR018733/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120912
PL  - United States
TA  - Tissue Eng Part A
JT  - Tissue engineering. Part A
JID - 101466659
RN  - 0 (Angiogenic Proteins)
RN  - 0 (Endothelial Growth Factors)
SB  - IM
MH  - Angiogenic Proteins/*metabolism
MH  - Animals
MH  - Batch Cell Culture Techniques/methods
MH  - Blood Vessels/*cytology/*growth & development
MH  - Cell Communication/physiology
MH  - Cells, Cultured
MH  - Embryonic Stem Cells/*cytology/metabolism
MH  - Endothelial Cells/*cytology/metabolism
MH  - Endothelial Growth Factors/metabolism
MH  - Humans
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Mice
MH  - Umbilical Veins/*cytology/metabolism
PMC - PMC3530951
EDAT- 2012/09/14 06:00
MHDA- 2013/07/10 06:00
PMCR- 2014/01/01
CRDT- 2012/09/14 06:00
PHST- 2012/09/14 06:00 [entrez]
PHST- 2012/09/14 06:00 [pubmed]
PHST- 2013/07/10 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.1089/ten.tea.2011.0408 [pii]
AID - 10.1089/ten.tea.2011.0408 [doi]
PST - ppublish
SO  - Tissue Eng Part A. 2013 Jan;19(1-2):211-23. doi: 10.1089/ten.tea.2011.0408. Epub 
      2012 Sep 12.