TY - JOUR
T1 - Multipotent adult progenitor cells sustain function of ischemic limbs in mice
AU - Aranguren, Xabier L.
AU - McCue, Jonathan D.
AU - Hendrickx, Benoit
AU - Zhu, Xiao Hong
AU - Du, Fei
AU - Chen, Eleanor
AU - Pelacho, Beatriz
AU - Peñuelas, Ivan
AU - Abizanda, Gloria
AU - Uriz, Maialen
AU - Frommer, Sarah A.
AU - Ross, Jeffrey J.
AU - Schroeder, Betsy A.
AU - Seaborn, Meredith S.
AU - Adney, Joshua R.
AU - Hagenbrock, Julianna
AU - Harris, Nathan H.
AU - Zhang, Yi
AU - Zhang, Xiaoliang
AU - Nelson-Holte, Molly H.
AU - Jiang, Yuehua
AU - Billiau, An D.
AU - Chen, Wei
AU - Prósper, Felipe
AU - Verfaillie, Catherine M.
AU - Luttun, Aernout
PY - 2008/2/1
Y1 - 2008/2/1
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI31153
DO - 10.1172/JCI31153
M3 - Article
C2 - 18172550
AN - SCOPUS:38849199383
SN - 0021-9738
VL - 118
SP - 505
EP - 514
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 2
ER -
