Shielded Bone Marrow Research Articles

The factors controlling stem cell recirculation. i. Migration of hemopoietic stem cells in adrenalectomized mice

The influence of bilateral adrenalectomy on hemopoietic stem cell (CFU) migration in mice has been studied. Formation of endogenous spleen colonies in lethally irradiated, leg-shielded mice was sharply increased by prior adrenalectomy, and this increase was not dependent on the volume of shielded bone marrow. Adrenalectomy was shown to increase endogenous spleen colony formation in sublethally irradiated mice as well. However, it had no affect on formation of spleen colonies in lethally irradiated mice injected with syngeneic bone marrow. The CFU content of murine bone marrow decreased acutely after removal of the adrenals, and this decrease was accompanied by a concomitant increase in the peripheral blood and splenic CFU. Thus, adrenalectomy appeared to have no affect on the splenic plating efficiency or proliferative rate of hemopoietic stem cells, but it did result in increased migration of stem cells from the bone marrow to the blood, and thence to the spleen. It is concluded that the adrenal steroids may be of physiologic importance in the regulation of ehmopoietic stem cell migration.

The Response of Rabbit Lymphocytes to Mitogens and Alloantigens: Evidence for T Cell Heterogeneity

Abstract Soluble concanavalin A (Con A), phytohemagglutinin-P (PHA), and pokeweed mitogen (PWM) stimulate DNA synthesis in cells from a variety of normal rabbit lymphoid organs. In lethally irradiated rabbits injected with thymocytes, these responses are virtually normal or, in some instances, increased. In thymus-deprived animals (thymectomy, lethal irradiation, bone marrow shielding) they are virtually abolished. We conclude that the substances tested are specific T cell mitogens in the rabbit, as in other species. The response to Con A is both of higher magnitude and wider distribution among various lymphoid organs than the response to either of the other two mitogens. Responses to PHA relative to Con A vary in different organs, being lowest in thymus and highest in popliteal lymph nodes and manually separated cells of the thymus-dependent area (TDA) of the appendix. PHA-responsive cells were found to have the same organ distribution as cells responding in the one-way mixed lymphocyte reaction (MLR). It is proposed that responsiveness to PHA develops only in differentiated, peripheral T cells and that the PHA/Con A response ratio provides a convenient index in the rabbit for estimating function in these cell populations. The appendix TDA was enriched in cells responsive to T cell mitogens and in the MLR relative to whole appendix as well as to the dome and follicle components of this organ. This finding confirms other evidence that this morphologic element of the gut-associated lymphoid tissue (GALT) is thymus-dependent. A small proportion of rabbit B lymphocytes, limited largely to peripheral lymph nodes, were shown to respond to endotoxic lipopolysaccharide. As is the case in other animals, PWM appears to be mitogenic for both T and B cells in the rabbit.

Effect of prior splenectomy on hematologic tolerance during total lymphoid radiotherapy of patients with Hodgkin's disease.

CancerVolume 27, Issue 2 p. 471-478 ArticleFree Access Effect of prior splenectomy on hematologic tolerance during total lymphoid radiotherapy of patients with Hodgkin's disease John R. Salzman, John R. Salzman Department of Radiology, Stanford University Medical Center, Stanford, Calif. Mr. Salzman compiled much of the data contained in this paper during a 3-month clerkship in radiation therapy at Stanford University Medical Center in the summer of 1969.Search for more papers by this authorHenry S. Kaplan, Henry S. Kaplan Department of Radiology, Stanford University Medical Center, Stanford, Calif.Search for more papers by this author John R. Salzman, John R. Salzman Department of Radiology, Stanford University Medical Center, Stanford, Calif. Mr. Salzman compiled much of the data contained in this paper during a 3-month clerkship in radiation therapy at Stanford University Medical Center in the summer of 1969.Search for more papers by this authorHenry S. Kaplan, Henry S. Kaplan Department of Radiology, Stanford University Medical Center, Stanford, Calif.Search for more papers by this author First published: February 1971 https://doi.org/10.1002/1097-0142(197102)27:2<471::AID-CNCR2820270236>3.0.CO;2-6Citations: 46 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 Boutis, L., Hoffmann, P., and Musshoff, K.: Veränderungen im peripheren Blutbild während und nach einer systematischen Bestrahlung bei der Lymphogranulomatose. Strahlentherapie 133: 539– 548, 1967. 2 Ellis, R. E.: The distribution of active bone marrow in the adult. Phys. Med. Biol. 5: 255– 258, 1961. 3 Enright, L. P., Trueblood, H. W., and Nelsen, T. S.: The surgical diagnosis of abdominal Hodgkin's disease. Surg. Gynec. Obstet. 130: 853– 858, 1970. 4 Glatstein, E., Guernsey, J. M., Rosenberg, S. A., and Kaplan, H. S.: The value of laparotomy and splenectomy in the staging of Hodgkin's disease. Cancer 24: 709– 718, 1969. 5 Goswitz, F. A., Andrews, G. A., and Kniseley, R. M.: Effects of local irradiation (Co60 teletherapy) on the peripheral blood and bone marrow. Blood 21: 605– 619, 1963. 6 Hanks, G. E.: In vivo migration of colony-forming units from shielded bone marrow in the irradiated mouse. Nature 203: 1393– 1395, 1964. 7 Hellman, S., and Fink, M. E.: Granulocyte reserve following radiation therapy as studied by the response to a bacterial endotoxin. Blood 25: 310– 324, 1965. 8 Johnson, R. E., Kagan, A. R., Haftermann, M. D., and Keyes, J. W., Jr.: Patient tolerance to extended irradiation in Hodgkin's disease. Ann. Intern. Med. 70: 1– 6, 1969. 9 Kaplan, H. S.: On the natural history, treatment, and prognosis of Hodgkin's disease. Harvey Lectures, 1968–69 (In press). 10 Kaplan, H. S., and Rosenberg, S. A.: Extended-field radical radiotherapy in advanced Hodgkin's disease; short-term results of 2 randomized clinical trials. Cancer Res. 26: 1268– 1276, 1966. 11 Tubiana, M., Rambert, P., Laugier, A., and Lalanne, C. M.: Les irradiations étendues dans la maladie de Hodgkin. Réactions précoces. Nouv. Rev. Franc. Hemat. 6: 164– 174, 1966. 12 Vogel, J. M., Kimball, H. R., Foley, H. T., Wolff, S. M., and Perry, S.: Effect of extensive radiotherapy on the marrow granulocyte reserves of patients with Hodgkin's disease. Cancer 21: 798– 804, 1968. 13 Woodard, H. D., and Holodny, E.: A summary of the data of Mechanik on the distribution of human bone marrow. Phys. Med. Biol. 5: 57– 59, 1960. Citing Literature Volume27, Issue2February 1971Pages 471-478 ReferencesRelatedInformation

The influence of the bone marrow on the repopulation of the thymus in X-irradiated mice

A quantitative cellular study of the irradiated mouse thymus and bone marrow has been presented. The bone marrow cells were classified into two populations, according to their volume. One of these cell populations is mainly composed of lymphocytic and the other of granulocytic cells. These two populations showed dissimilar repopulation patterns after whole body irradiation. The thymus cell population exhibited a repopulation pattern closely resembling that of the bone marrow lymphocyte population, both after whole and partial body irradiation. Bone marrow shielding during a second irradiation, 8–26 days after the first one, accelerated the thymus repopulation if the second dose was given at a time when the bone marrow was composed predominantly of small cells. An attempt was also made to purify the bone marrow lymphocytes by treating bone marrow cells in vitro with desoxycholate. It was observed that transplantation of desoxycholate-resistant cells into lethally irradiated mice induced an earlier repopulation of the thymus than an equal number of normal bone marrow cells.

Erythropoiesis in the rat under continuous gamma-irradiation at 45 rads-day.

SUMMARYRadioactive iron has been used to study the response of erythropoiesis in rats during continuous γ‐irradiation at 45 rads/day. Haemoglobin and haematocrit values remain very nearly normal throughout the period of 19 weeks studied and there is only a small decrease in the red cell count at times later than 10 weeks. The lower than normal59Fe incorporation occurring during the first few weeks of irradiation appreciably underestimates red cell production. The marked fall in re‐populating ability indicates a considerable change in the mechanism by which red cell production is maintained after more than 6 weeks irradiation. The recovery of re‐populating ability following the termination of the irradiation after a period of 10 weeks suggests that 30 per cent of the re‐populating cells are killed each day by the continuous irradiation. The results presented do not show at which stage of erythropoiesis increased proliferation occurs. However, if all the increased proliferation should occur in the cells with re‐populating ability, an increase of 10–15 times would be required in their proliferation rate. An alternative method that has been proposed for measuring re‐populating ability employing irradiation with bone marrow shielding, instead of bone marrow transplantation is briefly discussed.

Prevention of the bone-marrow syndrome in irradiated mice. A comparison of the results after bone-marrow shielding and bone-marrow inoculation.

SummaryShielding of bone-marrow in irradiated mice was compared with intravenous injection of a bone-marrow cell suspension in its effectiveness to prevent a bone-marrow syndrome. Three criteria were used to measure this effectiveness: (a) survival of the irradiated mouse at 30 days after irradiation; (b) re-population of irradiated haematopoietic tissues, and (c) incidence of spleen colonies.On the basis of the number of cells involved bone-marrow injection appeared to be about 100 times more effective than bone-marrow shielding.

IN VIVO MIGRATION OF COLONY-FORMING UNITS FROM SHIELDED BONE MARROW IN THE IRRADIATED MOUSE.

THE early bone marrow and spleen shielding experiments of Storer1, Kaplan2 and Jacobson3 first indicated that haematopoietic stem cells were capable of migration and repopulation of X-irradiation depleted haematopoietic tissues. Popp4 and Goodman5 then showed that buffy coat obtained from the peripheral blood of mice contained cells capable of producing mature erythrocytes, lymphocytes and granulocytes. Trobaugh6 has recently demonstrated that peripheral blood of the mouse contains cells capable of forming colonies in the spleen of irradiated recipients. He finds peripheral blood contains about 1 per cent of the number of colony-forming units (CFU) found in bone marrow, when comparing total nucleated cells injected. Hellman7 reports granulocyte counts in the peripheral blood of the mouse recovered more slowly when partial body irradiation is given during 2 h, when compared with similar dosage delivered in a few minutes. He concludes this is due to killing of circulating stem cells.

Cellularity and Deoxyribonucleic Acid Synthesis in Bone Marrow after Total- and Partial-Body Irradiation

Rats were exposed to 600 r, and the cellularity, cytology, and ability to synthesize DNA by using H/sup 3/-thymidine and autoradiography were studied in the erythroid precursors over the first 24 hours after exposure. The loss of red cell precursors was early and profound, most marked in the younger forms. The number of cells capable of being labeled during DNA synthesis in all maturation compartments decreased considerably more rapidly than did the total number of similsr cells, or the number of similar cells not in DNA synthesis. Some of the marked effect on DNA-synthesizing ability was due to an inhibition or to a decreased rate of the actual process of DNA synthesis as indicated by reduced grain counts. However, some was probably due to normal movement of cells out of the DNA synthesis phase, with failure of replacement due to cell death and/or delay of cells entering DNA synthesis. Effects of the exposure on the number of mitotic figures and on cytology are described. A slight and transient effect in shielded bone marrow on the number oi labeled cells, the grain count, and the number of mitotic figures was observed. (auth)

Hematologic Changes in Rats Protected from Lethal X-Radiation by Post-Irradiation Parabiosis

Since its introduction by Brecher and Cronkite (1), post-irradiation parabiosis has served as a satisfactory means of protection of experimental animals from lethal amounts of X-radiation. The mechanism of this protection has remained obscure, however. The state of parabiosis is characterized by a relatively large exchange of blood between the two partners (2), and it is thought that this exchange may transmit the protective factors. The importance of the hemapoietic system in protection from irradiation damage has been indicated by other methods, such as spleen or bone marrow shielding (3, 4) or injection of spleen or bone marrow homogenates (5, 6). Previous pre-irradiation parabiosis studies have demonstrated exchange of leucocytes and erythrocytes and have shown that the damage to the parabiont is not as severe as that of the single animal, presumably owing to the cross circulation (7, 8). It is the purpose of the present experiment to investigate the hematologic aspects of post-irradiation parabiosis, i.e., surgical union after X-radiation, in an attempt to elucidate the role of circulating blood in protection from radiation injury.