Biochemical changes and increased liver weight in bone marrow chimeras

1961 ◽  
Vol 200 (1) ◽  
pp. 102-106 ◽  
Author(s):  
A. L. Kretchmar ◽  
C. C. Congdon

Female mice of two different strains were x-irradiated (950 or 900 r total-body) and then given 40 x 106 bone marrow cells from the same or a different strain of female donor mice. Irradiated mice lost weight during the 1st week after treatment. Mice given bone marrow cells showed good recovery except that when the cells were from a different strain there was a second weight loss persisting to the 35th day. The liver weight increased after treatment. The maximum was noted at 12 days. Glutamine and glutathione concentration in livers of treated mice was reduced at 12 days and the concentration of ß-aminoisobutyric acid and of ß-alanine was increased. The changes were greatest in animals given bone marrow cells of a different strain.

Blood ◽  
1997 ◽  
Vol 89 (7) ◽  
pp. 2376-2383 ◽  
Author(s):  
Ronald van Os ◽  
Donald Dawes ◽  
John M.K. Mislow ◽  
Alice Witsell ◽  
Peter M. Mauch

Abstract Administration of kit-ligand (KL) before and after doses of 5-fluorouracil (5-FU) results in marrow failure in mice, presumably because of enhanced KL-induced cycling of stem cells, which makes them more susceptible to the effects of 5-FU. In attempt to capitalize on this effect on stem cells, we studied the ability of KL and 5-FU to allow stable donor engraftment of congenically marked marrow in a C57BL/6 (B6) mouse model. KL was administered subcutaneously at 50 μg/kg, 21 hours and 9 hours before and 3 hours after each of two doses of 5-FU (125 mg/kg) given 7 days apart to B6-recipients. Animals then received three injections of 107 congenic B6-Gpi-1a-donor bone marrow cells at 24, 48, and 72 hours after the second 5-FU dose. A separate group of animals received a single dose of either 1 × 107 or 3 × 107 donor marrow cells 24 hours after the last 5-FU dose. The level of engraftment was measured from Gpi-phenotyping at 1, 3, 6, and 8 months in red blood cells (RBCs) and at 8 months by phenotyping cells from the thymus, spleen, and marrow. Percent donor engraftment in RBCs appeared stable after 6 months. The percent donor engraftment in RBCs at 8 months was significantly higher in KL + 5-FU prepared recipients (33.0 ± 2.7), compared with 5-FU alone (18.5 ± 2.6, P < .0005), or saline controls (17.8 ± 1.7, P < .0001). In an additional experiment, granulocyte colony-stimulating factor (100 μg/dose) was added to a reduced dose of KL (12.5 μg/dose); engraftment was similar to KL alone. At 8 months after transplantation the levels of engraftment in other tissues such as bone marrow, spleen, and thymus correlated well with erythroid engraftment to suggest that multipotent long-term repopulating stem cells had engrafted in these animals. There are concerns for the toxicity of total body irradiation (TBI)- or busulfan-based regimens in young recipients of syngeneic or transduced autologous marrow who are transplanted for correction of genetic disease. In these recipients complete donor engraftment may not be needed. The results with KL and 5-FU are encouraging for the further refinement of non-TBI, nonbusulfan techniques to achieve stable mixed chimerism.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3178-3178
Author(s):  
Zhong Chao Han ◽  
Bin Liu ◽  
Lihua Zhao

Abstract In cancer therapy, specific radioprotection of normal tissue and antiangiogenesis are the ways to increase the therapeutic gain. Here we describe a novel gene therapy, which uses attenuated salmonella SL3261 as oral vectors carrying with cDNA of platelet factor 4 (PF4) or that of a truncated PF4. After oral administrations of attenuated salmonella carrying with cDNA of PF4 or truncated PF4, the survival rate of mice which received sublethal total body irradiation was improved by 50%, In comparison with the control mice, the bone marrow cells obtained from the mice of experimental group increased (13.2±8.3, 15.7±1.5 vs 4.1 ± 2.0 P<0.05) at day 7 after TBI, and the number of HPP-CFC of bone marrow cells also increased significantly (15.7±9, 11.7±5 vs 4.3±4.1 P<0.05) at day 7, suggesting a stimulating effect of PF4 on hematopoietic recovery. This gene therapy also caused significant tumor regression. The microvessel density (MVD) of tumors was significantly decreased in the group of treated mice compared to controls (4.25±0.96, 4.08±0.56 vs 11±0.83 P<0.05). Analysis TUNEL kit revealed an increase in the number of apoptosis cells in tumors of mice treated by SL3261 carrying with cDNA of PF4 or a truncated PF4. GFP expression and gene integration were detected in the liver, kidney, spleens, intestine, peripheral blood, bone marrow and tumors samples of the SL3261 treated mice, and the expression of GFP was higher in tumors than that in other tissues. These data demonstrate for the first time a dual biological function of PF4 against tumor growth and radiation injury. These results also demonstrate that attenuated salmonella can be used in vivo as a DNA delivery vector


1973 ◽  
Vol 138 (1) ◽  
pp. 130-142 ◽  
Author(s):  
Varda Rotter ◽  
Amiela Globerson ◽  
Ichiro Nakamura ◽  
Nathan Trainin

The immune response to SRBC was measured in the spleens of adult thymectomized, total body irradiated mice injected with various combinations of thymus and bone marrow cells together with thymic humoral factor (THF). It was found that the number of plaque-forming cells was significantly increased when THF was given in vivo immediately after thymus cell administration or when thymus cells were incubated in THF before injection. On the other hand, bone marrow cells equally treated did not manifest any T cell activity, since THF-treated bone marrow cells were not able to substitute thymus cells in the system used. The results accumulated in the present experiments indicate, therefore, that the target cells for THF activity are thymus cells which acquire a higher T helper cell capacity after THF treatment.


Blood ◽  
1971 ◽  
Vol 37 (6) ◽  
pp. 634-646 ◽  
Author(s):  
PERETZ RESNITZKY ◽  
DOV ZIPORI ◽  
NATHAN TRAININ

Abstract The influence of neonatal thymectomy on the behavior of hemopoietic stem cells of bone marrow and spleen was investigated by studying the colony-forming capacity (CFC) of these cells. Bone marrow cells (2 x 104) from neonatally thymectomized C3H mice, injected into lethally irradiated (850 R) recipients, showed a reduced CFC in relation to that of intact control donors. This decrease, which was more evident in female than in male mice, started early in life after thymectomy, and persisted throughout all the ages investigated. In most of the experiments a concomitant decrease in the total number of nucleated bone marrow cells was observed following thymectomy. When spleen cells (105) from neonatally thymectomized mice were tested under similar experimental conditions, they manifested a CFC equivalent to that of intact controls. Neonatal thymectomy increased the number of spontaneous colonies appearing in the spleen of mice after a sublethal (650 R) total-body irradiation. In contrast, when neonatal splenectomy was tested, a moderate increase in the CFC of bone marrow and in the total number of bone marrow cells was observed. The present results suggest that the thymus plays a role in the proliferative pattern of hemopoietic stem (progenitor) cells located in the bone marrow, whereas it does not influence the behavior of more mature (precursor) hemopoietic cells populating the spleen.


2003 ◽  
Vol 3 (3) ◽  
pp. 445-455 ◽  
Author(s):  
Oladipo A Oredipe ◽  
Paulette M Furbert-Harris ◽  
Ibrahim Laniyan ◽  
William R Green ◽  
Sandra L White ◽  
...  

1992 ◽  
Vol 12 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Pilar Sancho ◽  
Elvira Cuenllas ◽  
Soledad Gaitan ◽  
Concepción Tejero

The effect of total body irradiation (5 Gy) on functional mouse erythroid lineage has been studied. The transferrin binding capacity by bone marrow cells and the activity of glycolytic regulatory enzymes and intracellular levels of 2,3 bisphosphoglycerate in peripheral blood erythrocytes have been determined. Results obtained along one year post-irradiation period suggest a complete recovery in the erythroid cell lineage with respect to the biological endpoints investigated.


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