Multipotent adult progenitor cells sustain function of ischemic limbs in mice
Aranguren XL, McCue JD, Hendrickx B, Zhu XH, Du F, Chen E, Pelacho B, Peñuelas I, Abizanda G, Uriz M, Frommer SA, Ross JJ, Schroeder BA, Seaborn MS, Adney JR, Hagenbrock J, Harris NH, Zhang Y, Zhang X, Nelson-Holte MH, Jiang Y, Billiau AD, Chen W, Prósper F, Verfaillie CM, Luttun A.
Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium.
Despite progress in cardiovascular research, a cure for peripheral vascular disease has not been found. We compared the vascularization and tissue regeneration potential of murine and human undifferentiated multipotent adult progenitor cells (mMAPC-U and hMAPC-U), murine MAPC-derived vascular progenitors (mMAPC-VP), and unselected murine BM cells (mBMCs) in mice with moderate limb ischemia, reminiscent of intermittent claudication in human patients. mMAPC-U durably restored blood flow and muscle function and stimulated muscle regeneration, by direct and trophic contribution to vascular and skeletal muscle growth.
This was in contrast to mBMCs and mMAPC-VP, which did not affect muscle regeneration and provided only limited and transient improvement. Moreover, mBMCs participated in a sustained inflammatory response in the lower limb, associated with progressive deterioration in muscle function. Importantly, mMAPC-U and hMAPC-U also remedied vascular and muscular deficiency in severe limb ischemia, representative of critical limb ischemia in humans.
Thus, unlike BMCs or vascular-committed progenitors, undifferentiated multipotent adult progenitor cells offer the potential to durably repair ischemic damage in peripheral vascular disease patients.
CITA DEL ARTÍCULO J Clin Invest. 2008 Feb;118(2):505-14.