TIE2‐expressing monocytes/macrophages regulate revascularization of the ischemic limb
TIE2‐expressing monocytes/macrophages regulate revascularization of the ischemic limb
About this item
Full title
Author / Creator
Patel, Ashish S. , Smith, Alberto , Nucera, Silvia , Biziato, Daniela , Saha, Prakash , Attia, Rizwan Q. , Humphries, Julia , Mattock, Katherine , Grover, Steven P. , Lyons, Oliver T. , Guidotti, Luca G. , Siow, Richard , Ivetic, Aleksandar , Egginton, Stuart , Waltham, Matthew , Naldini, Luigi , De Palma, Michele and Modarai, Bijan
Publisher
London: Nature Publishing Group UK
Journal title
Language
English
Formats
Publication information
Publisher
London: Nature Publishing Group UK
Subjects
More information
Scope and Contents
Contents
A third of patients with critical limb ischemia (CLI) will eventually require limb amputation. Therapeutic neovascularization using unselected mononuclear cells to salvage ischemic limbs has produced modest results. The TIE2‐expressing monocytes/macrophages (TEMs) are a myeloid cell subset known to be highly angiogenic in tumours. This study aimed to examine the kinetics of TEMs in patients with CLI and whether these cells promote neovascularization of the ischemic limb. Here we show that there are 10‐fold more circulating TEMs in CLI patients, and removal of ischemia reduces their numbers to normal levels. TEM numbers in ischemic muscle are two‐fold greater than normoxic muscle from the same patient. TEMs from patients with CLI display greater proangiogenic activity than TIE2‐negative monocytes
in vitro
. Using a mouse model of hindlimb ischemia, lentiviral‐based
Tie2
knockdown in TEMs impaired recovery from ischemia, whereas delivery of mouse macrophages overexpressing TIE2, or human TEMs isolated from CLI patients, rescued limb ischemia. These data suggest that enhancing TEM recruitment to the ischemic muscle may have the potential to improve limb neovascularization in CLI patients.
→See accompanying articles
http://dx.doi.org/10.1002/emmm.201302695
and
http://dx.doi.org/10.1002/emmm.201302794
Graphical Abstract
Tie2‐expressing macrophages (TEMs) have the potential to improve revascularization of the ischemic limb and may therefore, represent an attractive novel cell therapy for promoting limb salvage in pa...
Alternative Titles
Full title
TIE2‐expressing monocytes/macrophages regulate revascularization of the ischemic limb
Authors, Artists and Contributors
Author / Creator
Identifiers
Primary Identifiers
Record Identifier
TN_cdi_doaj_primary_oai_doaj_org_article_b83ba7e8ad9049e58ab75866b5d9556d
Permalink
https://devfeature-collection.sl.nsw.gov.au/record/TN_cdi_doaj_primary_oai_doaj_org_article_b83ba7e8ad9049e58ab75866b5d9556d
Other Identifiers
ISSN
1757-4676
E-ISSN
1757-4684
DOI
10.1002/emmm.201302752
