Ex vivo activated immune cells promote survival and stimulate multilineage hematopoietic recovery in myelosuppressed mice.
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.
Li
Gong
G
Department of Oncology, Liu Hua Qiao Hospital, Guangzhou, China.
Wang
Xiaohuai
X
Wu
Lubo
L
Zhang
Weimin
W
Chen
Huiyu
H
Xie
Yongfu
Y
Yang
Demao
D
D000741:Anemia, Aplastic / Q000209:etiology / Q000628:therapy*; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D016190:Carboplatin / Q000633:toxicity; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004906:Erythrocyte Count; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D007166:Immunosuppressive Agents / Q000633:toxicity; D007376:Interleukin-2 / Q000494:pharmacology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D038042:Myelopoiesis / Q000187:drug effects* / Q000528:radiation effects; D010976:Platelet Count; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology; D015996:Survival Rate; D014183:Transplantation, Heterologous; D014185:Transplantation, Isogeneic; D014916:Whole-Body Irradiation / Q000009:adverse effects
D018952:Antigens, CD34; D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016190:Carboplatin