Abstract
Recovery of multilineage hematopoiesis from severe myelosuppression due to chemotherapy and radiotherapy remains a clinical problem. The authors have developed a simple immunotherapy to treat this disease in a mouse model. Syngeneic spleen cells or xenogeneic human peripheral mononuclear cells were cultured ex vivo with a combination of IL-2 at 500 IU/mL, GM-CSF at 200 U/mL, and calcium ionophore A23187 at 100 ng/mL for 2 days and injected intravenously into mice that had previously received a lethal dose of carboplatin and radiation. The therapy was highly effective: a single injection of activated cells enhanced survival and simulated multilineage recovery of hematopoiesis. Ex vivo activated immune cells produced multiple cytokines, including several hematopoietic growth factors. Adherent cells were found to be more potent than nonadherent cells in promoting survival, and the therapy alone was capable of mobilizing peripheral blood stem cells in normal mice.
MeSH terms
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Anemia, Aplastic / etiology
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Anemia, Aplastic / therapy*
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Animals
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Antigens, CD34 / analysis
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Bone Marrow / drug effects
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Bone Marrow / pathology
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Bone Marrow / radiation effects
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Carboplatin / toxicity
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Cell Movement / drug effects
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Cell Movement / immunology
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Cell Transplantation / methods*
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Cells, Cultured
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Cytokines / metabolism
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Erythrocyte Count
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Female
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Humans
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Immunization, Passive / methods*
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Immunosuppressive Agents / toxicity
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Interleukin-2 / pharmacology
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Leukocyte Count
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / metabolism
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Leukocytes, Mononuclear / transplantation
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Mice
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Mice, Inbred BALB C
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Myelopoiesis / drug effects*
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Myelopoiesis / radiation effects
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Platelet Count
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Spleen / cytology
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Stem Cells / chemistry
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Stem Cells / cytology
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Survival Rate
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Transplantation, Heterologous
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Transplantation, Isogeneic
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Whole-Body Irradiation / adverse effects
Substances
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Antigens, CD34
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Cytokines
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Immunosuppressive Agents
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Interleukin-2
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Granulocyte-Macrophage Colony-Stimulating Factor
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Carboplatin