Mesenchymal stem cells can participate in ischemic neovascularization.
Authors Hamou C, Callaghan MJ, Thangarajah H, Chang E, Chang EI, Grogan RH, Paterno J,
Vial IN, Jazayeri L, Gurtner GC
Submitted By Geoffrey Gurtner on 3/31/2010
Status Published
Journal Plastic and reconstructive surgery
Year 2009
Date Published 2/1/2009
Volume : Pages 123 : 45S - 55S
PubMed Reference 19182663
Abstract BACKGROUND: Cells from the bone marrow contribute to ischemic
neovascularization, but the identity of these cells remains unclear. The authors
identify mesenchymal stem cells as a bone marrow-derived progenitor population
that is able to engraft into peripheral tissue in response to ischemia. METHODS:
A murine model of skin ischemia was used. Bone marrow, blood, and skin were
harvested at different time points and subjected to flow cytometric analysis for
mesenchymal and hematopoietic markers (n = 3 to 7 per time point). Using a
parabiotic model pairing donor green fluorescent protein (GFP)-positive with
recipient wild-type mice, progenitor cell engraftment was examined in ischemic
tissue by fluorescence microscopy, and engrafted cells were analyzed by flow
cytometry for endothelial and mesenchymal markers. In vitro, the ability of both
bone marrow- and adipose-derived mesenchymal stem cells to adopt endothelial
characteristics was examined by analyzing (1) the ability of mesenchymal stem
cells to take up DiI-acetylated low-density lipoprotein and Alexa Fluor lectin,
and (2) phenotypic changes of mesenchymal stem cells co-cultured with
GFP-labeled endothelial cells or under hypoxic/vascular endothelial growth
factor stimulation. RESULTS: In vivo, the bone marrow mesenchymal stem cell
population decreased significantly immediately after surgery, with subsequent
engraftment of these cells in ischemic tissue. Engrafted cells lacked the
panhematopoietic antigen CD45, consistent with a mesenchymal origin. In vitro,
bone marrow- and adipose-derived mesenchymal stem cells took up DiI-acetylated
low-density lipoprotein and Alexa Fluor lectin, and expressed endothelial
markers under hypoxic conditions. CONCLUSIONS: The authors' data suggest that
mesenchymal precursor cells can give rise to endothelial progenitors.
Consequently, cell-based therapies augmenting the mesenchymal stem cell
population could represent powerful alternatives to current therapies for
ischemic vascular disease.

Investigators with authorship
Geoffrey GurtnerStanford University


Ptprcprotein tyrosine phosphatase, receptor type, C