PMID- 23959047
OWN - NLM
STAT- MEDLINE
DCOM- 20140220
LR  - 20220309
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1832
IP  - 12
DP  - 2013 Dec
TI  - Tumor necrosis factor-alpha-activated mesenchymal stem cells promote endothelial 
      progenitor cell homing and angiogenesis.
PG  - 2136-44
LID - S0925-4439(13)00267-6 [pii]
LID - 10.1016/j.bbadis.2013.08.002 [doi]
AB  - Mesenchymal stem cells (MSCs) accelerate regeneration of ischemic or injured 
      tissues by stimulation of angiogenesis through a paracrine mechanism. Tumor 
      necrosis factor-alpha (TNF-alpha)-activated MSCs secrete pro-angiogenic cytokines, 
      including IL-6 and IL-8. In the present study, using an ischemic hindlimb animal 
      model, we explored the role of IL-6 and IL-8 in the paracrine stimulation of 
      angiogenesis and tissue regeneration by TNF-alpha-activated MSCs. Intramuscular 
      injection of conditioned medium derived from TNF-alpha-treated MSCs (TNF-alpha CM) into 
      the ischemic hindlimb resulted in attenuated severe limb loss and stimulated 
      blood perfusion and angiogenesis in the ischemic limb. Immunodepletion of IL-6 
      and IL-8 resulted in attenuated TNF-alpha CM-stimulated tissue repair, blood 
      perfusion, and angiogenesis. In addition, TNF-alpha CM induced migration of human 
      cord blood-derived endothelial progenitor cells (EPCs) through IL-6- and 
      IL-8-dependent mechanisms in vitro. Intramuscular injection of TNF-alpha CM into the 
      ischemic limb led to augmented homing of tail vein-injected EPCs into the 
      ischemic limb in vivo and immunodepletion of IL-6 or IL-8 from TNF-alpha CM 
      attenuated TNF-alpha CM-stimulated homing of EPCs. In addition, intramuscular 
      injection of recombinant IL-6 and IL-8 proteins resulted in increased homing of 
      intravenously transplanted EPCs into the ischemic limb and improved blood 
      perfusion in vivo. These results suggest that TNF-alpha CM stimulates angiogenesis 
      and tissue repair through an increase in homing of EPCs through paracrine 
      mechanisms involving IL-6 and IL-8.
CI  - (c) 2013.
FAU - Kwon, Yang Woo
AU  - Kwon YW
AD  - Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, 
      Pusan National University, Yangsan, Republic of Korea; Department of Physiology, 
      School of Medicine, Pusan National University, Yangsan, Republic of Korea.
FAU - Heo, Soon Chul
AU  - Heo SC
FAU - Jeong, Geun Ok
AU  - Jeong GO
FAU - Yoon, Jung Won
AU  - Yoon JW
FAU - Mo, Won Min
AU  - Mo WM
FAU - Lee, Mi Jeong
AU  - Lee MJ
FAU - Jang, Il-Ho
AU  - Jang IH
FAU - Kwon, Sang Mo
AU  - Kwon SM
FAU - Lee, Jung Sub
AU  - Lee JS
FAU - Kim, Jae Ho
AU  - Kim JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130816
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adipocytes/cytology/drug effects/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - *Cell Movement
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/*pharmacology
MH  - Fluorescent Antibody Technique
MH  - Hindlimb/*blood supply/metabolism/pathology
MH  - Human Umbilical Vein Endothelial Cells/*cytology/drug effects/metabolism
MH  - Humans
MH  - Interleukin-6/deficiency/immunology
MH  - Interleukin-8/deficiency/immunology
MH  - Ischemia/*drug therapy/metabolism/pathology
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Necrosis
MH  - *Neovascularization, Physiologic
MH  - Stem Cells/*cytology/drug effects/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Wound Healing
OTO - NOTNLM
OT  - Angiogenesis
OT  - EPCs
OT  - Endothelial progenitor cells
OT  - Ischemia
OT  - MSCs
OT  - Mesenchymal stem cells
OT  - TNF-alpha
OT  - TNF-alpha CM
OT  - Tumor necrosis factor-alpha
OT  - conditioned medium derived from TNF-alpha-treated MSCs
OT  - endothelial progenitor cells
OT  - hASCs
OT  - human adipose tissue-derived MSCs
OT  - mesenchymal stem cells
OT  - tumor necrosis factor-alpha
EDAT- 2013/08/21 06:00
MHDA- 2014/02/22 06:00
CRDT- 2013/08/21 06:00
PHST- 2013/04/02 00:00 [received]
PHST- 2013/07/29 00:00 [revised]
PHST- 2013/08/11 00:00 [accepted]
PHST- 2013/08/21 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/02/22 06:00 [medline]
AID - S0925-4439(13)00267-6 [pii]
AID - 10.1016/j.bbadis.2013.08.002 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2013 Dec;1832(12):2136-44. doi: 
      10.1016/j.bbadis.2013.08.002. Epub 2013 Aug 16.