Improved arteriogenesis with simultaneous skeletal muscle repair in ischemic tissue by SCL plus 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. Conclusion: 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. Copyright (C) 2004 S. Karger AG, Basel.