Growth of human hematopoietic cells in immunodeficient mice conditioned with cyclophosphamide and busulfan.
Human hematopoietic cells survive and proliferate for at least 10 weeks in severe combined immunodeficient mice prepared with the cytotoxic drugs busulfan and cyclophosphamide. The human cells growing in the mice can be detected by in situ hybridization using a probe detecting human repetitive DNA or by staining the cells with antihuman antibodies (anti-CD45 and anti-HLA I). Busulfan/cyclophosphamide-treated mice were injected with a wide range of cell doses, ranging from 5 to 50 million unfractionated bone marrow cells and 2 to 40 million low density bone marrow cells. Animals were killed at 1, 3, 5, 7 and 10 weeks after transplantation. Human cells were found in many animals and could be detected as early as one week after transplantation. The peak of repopulation was at two to five weeks, but in some animals human cells could be detected for as long as 10 weeks. Many of the human cells expressed high levels of glycophorin, but mature human erythrocytes were not found. The human cells were not uniformly distributed throughout the marrow. They grew in small clusters in the subepiphyseal region. The extent of human hematopoietic repopulation in the mouse was extremely variable. At no time and at no dose was repopulation achieved in all of the animals. Treatment with human growth factors is not necessary for the survival of the human hematopoietic cells but, in their absence, normal hematopoiesis does not occur.
Basch
R S
RS
Department of Pathology, New York University Medical Center, New York, USA.
Quito
F L
FL
Beh
J
J
Hirst
J A
JA
D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D002066:Busulfan / Q000008:administration & dosage / Q000494:pharmacology*; D002452:Cell Count; D002455:Cell Division; D002469:Cell Separation; D002999:Clone Cells / Q000502:physiology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000502:physiology; D006021:Glycophorins / Q000096:biosynthesis; D006085:Graft Survival / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017403:In Situ Hybridization; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D013154:Spleen / Q000502:physiology; D013997:Time Factors; D019172:Transplantation Conditioning
D018952:Antigens, CD34; D006021:Glycophorins; D006133:Growth Substances; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D017493:Leukocyte Common Antigens; D002066:Busulfan