FACS-purified myoblasts producing controlled VEGF levels induce safe and stable angiogenesis in chronic hind limb ischemia.
Bottom Line: Vessel density was doubled in engrafted areas, but only approximately 0.1% of muscle volume showed cell engraftment, explaining why no increase in total blood flow was observed.In conclusion, the use of FACS-purified myoblasts granted the cell-by-cell control of VEGF expression levels, which ensured long-term safety in a model of chronic ischemia.Based on these results, the total number of implanted cells required to achieve efficacy will need to be determined before a clinical application.
Affiliation: Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital, Basel, Switzerland.Show MeSH
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Mentions: In order to investigate why the angiogenic induction observed by histological analysis was not accompanied by an increase in muscle blood flow, we examined the extent of stable engraftment of transduced myoblasts in the medial hamstring muscles 3 months after injection (n = 4 per condition). As can be seen in Figure 6A, X-Gal+ muscle fibres could only be found along the needle tract of the intramuscular injections (white arrows). The engraftment pattern was similar for the control rCD8 cells, the reference clone, the primary rVICD8 population and the purified population (Fig. 6B–E, respectively) and in all cases accounted for only approximately 0.1–0.2% of the total volume of the treated muscle (Fig. 6F).
Affiliation: Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital, Basel, Switzerland.