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 [SP], 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.
Magazine: The Journal of Clinical Investigation
Date: Feb 1, 2008Nuclear Medicine [SP] Cell Therapy Area [SP]
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.
CITATION J Clin Invest. 2008 Feb;118(2):505-14.
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