Autografting of genetically-modified bone marrow-derived mesenchymal stromal cells is undergoing laboratory and animal investigation to determine the feasibility of using it in the treatment of osteogenesis imperfecta in humans. 13,54,57,69,78 Autografting overcomes the allogeneic transplantation issues but introduces others relating to the safety and effectiveness of genetically-modified stromal cells. In this approach, bone marrow is harvested and ex vivo the mesenchymal stromal cells are isolated, expanded in numbers, and genetically modified, after which they then are reinfused into the donor. 54,57,62 Three types of genetic modification are being investigated in vitro and in rodents. In the first type, additional normal copies of the mutant gene are introduced into osteogenesis imperfecta mesenchymal stromal cells. 62,68,69 No attempt is made to inactivate the mutant allele. In the second type, the genetic modifications specifically are targeted to inactivate the mutant allele. 36,50,71,83 The latter approach likely will require a separate solution for each family with osteogenesis because few families and individuals share the same mutation. In the third type, other genes such as the human growth gene may be introduced into the osteogenesis imperfecta MSCs. 78 Genetically-modified MSCs have not been evaluated in humans with osteogenesis imperfecta.