Multipotent adult progenitor cells sustain function of ischemic limbs in mice

Xabier L. Aranguren, Jonathan D. McCue, Benoit Hendrickx, Xiao Hong Zhu, Fei Du, Eleanor Chen, Beatriz Pelacho, Ivan Peñuelas, Gloria Abizanda, Maialen Uriz, Sarah A. Frommer, Jeffrey J. Ross, Betsy A. Schroeder, Meredith S. Seaborn, Joshua R. Adney, Julianna Hagenbrock, Nathan H. Harris, Yi Zhang, Xiaoliang Zhang, Molly H. Nelson-HolteYuehua Jiang, An D. Billiau, Wei Chen, Felipe Prósper, Catherine M. Verfaillie, Aernout Luttun

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)505-514
Number of pages10
JournalJournal of Clinical Investigation
Volume118
Issue number2
DOIs
StatePublished - Feb 1 2008

Bibliographical note

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

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