Origin of endothelial progenitors in human postnatal bone marrow
J. Clin. Invest. Morayma Reyes, et al. 109:337 doi:10.1172/JCI14327 [
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Figure 6Contribution of human MAPC-derived endothelial cells to neoangiogenesis in tumors and wound healing. (
a–
g) MAPC-derived endothelial cells (0.25 × 10
6) (after 30–65 population doublings before differentiation) were injected intravenously into NOD-SCID mice after implantation of murine Lewis lung carcinoma spheroids (
n = 5) from three donors, aged 19, 28, and 31 years). After 2 weeks, animals were sacrificed, and tumors were removed, sectioned, and stained with either anti-human β2-microglobulin–FITC or anti-mouse CD31–FITC and anti–vWF-Cy3. Shown are the 3D reconstructed figures of 350 images for either anti-human β2-microglobulin–FITC (
c) or anti-mouse CD31–FITC (false colored as blue) (
d), and merging of the two (
e); anti–vWF-Cy3 (
f); and merging of the three staining patterns (
g). (
a and
b) Scale bar = 100 μm. (
h) Wound healing. Ears of NOD-SCID mice used in the studies described in
a were punched 3 and 5 days prior to intravenous injection of human MAPC-derived endothelial cells (
a–
c) or human foreskin fibroblasts (
d–
f). After 14 days, animals were sacrificed and ears were obtained and cryopreserved. Five-micrometer slides were stained with anti-human β2-microglobulin–FITC and anti–vWF-Cy3. Scale bar = 20 μm. C, cartilage; D, dermis. (
i) Tumor angiogenesis is derived from endothelial cells generated in vivo from MAPCs. MAPCs (10
6) (after 45 population doublings; donor age, 28 years) were injected intravenously into a NOD-SCID mouse (
n = 1). After 12 weeks, the animal was sacrificed, at which time a thymic tumor was detected. Ten-micrometer slides were stained with anti-human β2-microglobulin–FITC and anti–vWF-Cy3. Shown is a highly vascularized area in the tumor stained with Ab’s against β2-microglobulin–FITC, vWF, and TOPRO-3 (not shown). Scale bar = 20 μm.