Improved arteriogenesis with simultaneous skeletal muscle repair in ischemic tissue by SCL(+) multipotent adult progenitor cell clones from peripheral blood.
BACKGROUND
The CD34(-) murine stem cell line RM26 cloned from peripheral blood mononuclear cells has been shown to generate hematopoietic progeny in lethally irradiated animals. The peripheral blood-derived cell clones expresses a variety of mesodermal and erythroid/myeloid transcription factors suggesting a multipotent differentiation potential like the bone marrow-derived 'multipotent adult progenitor cells' (MAP-C).


METHODS
SCL(+) CD34(-) RM26 cells were transfused intravenously into mice suffering from chronic hind-limb ischemia, evaluating the effect of stem cells on collateral artery growth and simultaneous skeletal muscle repair.


RESULTS
RM26 cells are capable of differentiating in vitro into endothelial cells when cultured on the appropriate collagen matrix. Activation of the SCL stem cell enhancer (SCL(+)) is mediated through the binding to two Ets and one GATA site and cells start to express milieu- and growth condition-dependent levels of the endothelial markers CD31 (PECAM) and Flt-1 (VEGF-R1). Intravenously infused RM26 cells significantly improved the collateral blood flow (arteriogenesis) and neo-angiogenesis formation in a murine hind-limb ischemia transplant model. Although transplanted RM26 cells did not integrate into the growing collateral arteries, cells were found adjacent to local arteriogenesis, but instead integrated into the ischemic skeletal muscle exclusively in the affected limb for simultaneous tissue repair.


CONCLUSIONS
These data suggest that molecularly primed hem-/mesangioblast-type adult progenitor cells can circulate in the peripheral blood improving perfusion of tissues with chronic ischemia and extending beyond the vascular compartment.
Huss
Ralf
R
Institute of Pathology, University of Munich, Munich, Germany. Ralf.Huss@patho.med.uni-muenchen.de
Heil
Matthias
M
Moosmann
Sabine
S
Ziegelhoeffer
Tibor
T
Sagebiel
Sabine
S
Seliger
Christian
C
Kinston
Sarah
S
Gottgens
Berthold
B
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D002908:Chronic Disease; D003094:Collagen; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology; D004742:Enhancer Elements, Genetic / Q000502:physiology; D005263:Femoral Artery; D007511:Ischemia / Q000628:therapy*; D007797:Laminin; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D039902:Multipotent Stem Cells / Q000166:cytology; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010641:Phenotype; D010957:Plasmids; D011509:Proteoglycans; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000235:genetics
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D014157:Transcription Factors; C059485:matrigel; D003094:Collagen