Recent studies from the laboratory indicate that bone marrow stromal cells can engraft in normal and immune-deficient murine recipients. Human marrow stromal cells electrotransfected with a linearized bacterial plasmid carrying the human factor IX gene transcribed from the human immediate early CMV promoter engraft in unconditioned SCID mice. Circulating human factor IX levels can be detected in such recipients for up to 8 weeks after stromal cell infusion. In situ hybridization studies demonstrate the presence of human stromal cells in murine marrow up to 7 months after transplant. A Phase I study of genetically marked human marrow stromal cells infused into autotransplant recipients with delayed marrow engraftment was recently approved by the University of Toronto Human Experimentations Committee and the Health Protection Branch, Department of Health and Welfare, Government of Canada. Patient accrual commences in mid 1997. Further studies are planned to exploit genetically modified human marrow stromal cells as an attractive and non-toxic approach to gene therapy.
Armand Keating, MD
Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation Professor of Medicine, University of Toronto Senior Investigator, Oncology Research, The Toronto Hospital Research Institute