Multipotent adult progenitor cells sustain function of ischemic limbs in mice
J. Clin. Invest. Xabier L. Aranguren, et al. 118:505 doi:10.1172/JCI31153 [
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Figure 1mMAPC-U and hMAPC-U engraftment and differentiation. (
A–
F) At 14 days, cell patches (dotted lines in
A and
B) were found by in vivo (
A) or ex vivo (
B) imaging, GFP fluorescence (
C), and anti-GFP staining in cross sections (
D). Note positioning of the patches near α-SMA
+ (red in
E) vessels and the surrounding CD45
+ (red in
F) clusters. (
G–
I) At 14 days, confocal imaging revealed some GFP
+ cells coexpressing CD31 or α-SMA (arrowheads in
G and
H, respectively). A limited number of regenerating SkMBs were GFP
+ (thus donor derived; revealed by anti-GFP staining;
I). (
J–
L) At 5 weeks, mMAPC-U persisted (shown by in vivo imaging,
J; and anti-GFP staining,
K and
L). Note that donor-derived regenerating fibers (GFP
+ cells in
K) were still apparent and that cell number was less than it was at 14 days (compare
D and
L). (
M–
P) At 30 days, hMAPC-U stably engrafted (revealed by large human vimentin
+ [green] cell patches intercalated between muscle fibers [
M and
N] and as scattered cells around vessels [
P]). Cells were detected in the endothelial layer of vessels by a human-specific anti-CD31 antibody (green in
O), indicating EC differentiation, and in some cells the human vimentin signal (green) colocalized (yellow; white arrowheads) with α-SMA (red), indicating their SMC identity in
P. Images in
A,
C,
D,
E,
G–
J,
L,
M,
O, and
P are from adductor; images in
B,
F,
I, and
K from gastrocnemius and
N from quadriceps muscle. DAPI was used as nuclear counterstain in
C and
E and
M–
O and Topro (Molecular Probes) in
H and
P. Scale bars: 50 μm (
G–
I,
K), 100 μm (
C,
D,
F,
L,
M,
O, and
P), 200 μm (
E and
N), and 500 μm (
A,
B, and
J).