Contribution of human MAPC-derived endothelial cells to neoangiogenesis in tumors and wound healing. (a–g) MAPC-derived endothelial cells (0.25 × 10⁶) (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 (10⁶) (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.