Enhanced Engraftment of Genetically Modified Bone Marrow Stromal Cells

Résumé du livre

Transplantation of marrow stromal cells (MSC) shows promise as a vehicle for gene therapy. However, engraftment efficiency must be improved. To enhance homing and hence engraftment, we expressed VLA-4 on MSC to elicit interactions with adhesion molecules on marrow stem and stromal cells. Electroporation was used to transfect murine stromal cells with VLA-4 Ã chain cDNA. Cell surface VLA-4 expression and functional binding to VCAM-Ig were demonstrated by flow cytometry. Male MSC were infused into untreated or irradiated female Balb/c recipients with or without co-infusion of marrow cells. Male donor cells were detected by FISH or PCR for Y chromosome specific sequences. The highest level of MSC engraftment was with transfected MSC co-infused with marrow cells. The data show that stromal cell engraftment can be improved by almost 50 fold over infusion of unmodified stromal cells alone and suggest that this approach may have clinical utility.