To the author's knowledge, the rabbit is the largest animal model used to explore bone regeneration with genetically modified cells. This technology needs to be expanded to larger animal models that represent a more clinically relevant application in which cells are isolated from the animal, expanded ex vivo, genetically modified, and implanted in a critical-size bone defect in the donor animal. Furthermore, optimization of the vector type, vector dose, cell dose, and carrier material choice must be accomplished in animal models before clinical investigation is initiated. Most research has focused on a single osteoinductive protein; however, multiple proteins may synergize to further enhance bone formation. In conclusion, transplantation of genetically modified cells provides a new opportunity to improve bone tissue regeneration.