Lethally irradiated mice

FIGURE 2 9-3 Intravenous administration of stem cells can reconstitute the blood forming system, and may provide cells to other tissues. In classical studies, Till and McCulloch administered dissociated bone marrow cells in the tail vein of lethally irradiated mice and found that the grafted cells repopulated the hematopoietic system and allowed the animals to survive. More recent studies suggest that blood cells also travel to sites of injury, where they may give rise to non-blood-tissue progeny. 

Two observations suggest near normal function for rcel cells. First, loss of Rcelp minimally impacts hematopoiesis in otherwise normal tissue [46]. Second, adoptive transfer of murine rcel fetal liver cells rescues hematopoiesis in lethally irradiated mice. Moreover, tissue-specific loss of Rcelp in liver also results in otherwise healthy mice, as judged histologically and biochemically (i.e., transaminase activity) [11]. These... 

Gupta, M.L., S. Sankhwar, S. Verma, et al. 2008b. Whole body protection to lethally irradiated mice by oral administration of semipurified fraction of Podophyllum hexandrum and post irradiation treatment of Picrorhiza kurroa. Tokai. Exp. Clin. Med. 33(1) 6-12. 

The column technique has been applied to lymphocytes from non-im-munized mice as well (Wigzell and Makela, 1970). A mixture of normal lymph node, spleen and bone-marrow cells was passed through an OA-coated column. Column passed cells as well as control cells were transferred to lethally irradiated mice (10 cells per mouse) and followed by immunization with OA and BSA. The antibody content in the sera was detected by the Farr assay. There was no response to OA, while the response to BSA was normal. Control cell suspensions which were not subjected to the column passage resulted in a good response to both OA and BSA (Table 5). 

The second prediction was tested by Radovich and Talmage (1967). Lethally irradiated mice received transfers of 10 or 5 X 10 normal spleen cells on the same day as transfer, horse red cells were also injected and sheep red cells were given four days later. The results of the experiment showed, that contrary to what would be expected if the cells were uncommitted, the competition was more pronounced at the higher cell concentration. 

Chute, J. R, J. Fung, G. Muramoto et al. 2004a. Ex vivo culture rescues hematopoietic stem cells with longterm repopulating capacity following harvest from lethally irradiated mice. Exp Hematol32(3) 308-17. 

Although in vitro assays provide an indication of in vivo activity, in vivo assays are a better demonstration of HSC function. In vivo assays involve reconstitution of the hematopoietic system in immu-nodeficient or irradiated animal models. Spleen colony-forming unit (CFU-S) measures the abUity of HSCs to repopulate the spleens of lethally irradiated mice. However, CFU-S assays are short-term assays (approximately 12 days). Therefore, in vivo assays which examine the reconstitution of the entire hematopoietic system in immunodeficient or irradiated animal models for the lifetime of the animal are the only assays which truly identify HSCs. 

The ability of HSCs to switch from steady-state (maintenance) divisions to expansion is apparent in the bone marrow transplant assay. There are approximately 2 x 10 HSCs in an adult C57B1/6 mouse. A lethally irradiated mouse can be transplanted with2.5 x 10-bonemarrow mononuclear cells—containing... 

Chinese Herbal Medicines. Many traditional Chinese medicines have been screened for radioprotective activity in experimental animals. In one study of more than a thousand Chinese herbs, a number of agents increased the survival rate of dogs exposed to a lethal dose of y-rays by 30—40%, and some symptoms of radiation injury were ameHorated. These effects are potentially related to stimulation of the hemopoietic and immune systems (130). Extracts of five Chinese dmg plants, as weU as aspirin, effectively protected mice exposed to 7.5—8.0 Gy (750—800 rad) of y-radiation, and increased survival rates by 8—50% (131). Several Chinese traditional medicines, adininistered ip before or after irradiation, protected against Hpid peroxidation in a variety of mouse tissues, including BM, Hver, and spleen, as weU as in mouse Hver microsomal suspensions irradiated in vitro (132). 

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