Multipotent adult progenitor cells sustain function of ischemic limbs in mice.
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.
Aranguren
Xabier L
XL
Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium.
McCue
Jonathan D
JD
Hendrickx
Benoit
B
Zhu
Xiao-Hong
XH
Du
Fei
F
Chen
Eleanor
E
Pelacho
Beatriz
B
Peñuelas
Ivan
I
Abizanda
Gloria
G
Uriz
Maialen
M
Frommer
Sarah A
SA
Ross
Jeffrey J
JJ
Schroeder
Betsy A
BA
Seaborn
Meredith S
MS
Adney
Joshua R
JR
Hagenbrock
Julianna
J
Harris
Nathan H
NH
Zhang
Yi
Y
Zhang
Xiaoliang
X
Nelson-Holte
Molly H
MH
Jiang
Yuehua
Y
Billiau
An D
AD
Chen
Wei
W
Prósper
Felipe
F
Verfaillie
Catherine M
CM
Luttun
Aernout
A
D000818:Animals; D001808:Blood Vessels / Q000166:cytology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D005121:Extremities / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D032342:Muscle Cells / Q000166:cytology