FIG. 1.

Heterogeneous expression of human VEGF₁₆₅ induces only normal angiogenesis. (A) Maps of the bicistronic retroviral vectors carrying the coding sequence of murine VEGF (mVEGF₁₆₄) or human VEGF (hVEGF₁₆₅) and of a truncated version of murine or human CD8a (tr.CD8a), linked through an internal ribosome entry sequence (IRES). (B) Heterogeneous and high levels of expression of the VEGF-IRES-CD8 cassettes were detected by tracking mouse and human CD8a (mCD8 and hCD8, respectively) by flow cytometry in the primary populations of transduced myoblasts (red curves) and compared to nontransduced cells (negative control, green curves). (C) Whole-mount lectin staining (brown) of blood vessels 4 weeks after implantation of CD8 control cells (Ctrl CD8) and VEGF myoblasts expressing heterogeneous levels of either murine or human VEGF in the auricularis posterior muscle (n=5–8 for all groups). Myoblasts engraftment was tracked by X-Gal staining (blue). Heterogeneous murine VEGF levels caused the widespread growth of aberrant angioma-like structures, whereas heterogeneous human VEGF levels induced only morphologically normal capillaries. Size bar=50 μm in all panels. Color images available online at www.liebertpub.com/hgtb