title: Multipotent adult progenitor cells sustain function of ischemic limbs in mice.
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.
authors.affiliation: Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Xabier L
authors.initials: XL
authors.lastname: Aranguren
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: McCue
authors.forename: Benoit
authors.initials: B
authors.lastname: Hendrickx
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Zhu
authors.forename: Fei
authors.initials: F
authors.lastname: Du
authors.forename: Eleanor
authors.initials: E
authors.lastname: Chen
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelacho
authors.forename: Ivan
authors.initials: I
authors.lastname: Peñuelas
authors.forename: Gloria
authors.initials: G
authors.lastname: Abizanda
authors.forename: Maialen
authors.initials: M
authors.lastname: Uriz
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Frommer
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Ross
authors.forename: Betsy A
authors.initials: BA
authors.lastname: Schroeder
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Seaborn
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Adney
authors.forename: Julianna
authors.initials: J
authors.lastname: Hagenbrock
authors.forename: Nathan H
authors.initials: NH
authors.lastname: Harris
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Zhang
authors.forename: Molly H
authors.initials: MH
authors.lastname: Nelson-Holte
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Jiang
authors.forename: An D
authors.initials: AD
authors.lastname: Billiau
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
mesh_terms: 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