Hematopoietic reconstitution after lethal irradiation and bone marrow transplantation: effects of different hematopoietic cytokines on the recovery of thymus, spleen and blood cells

Frasca, Daniela; Guidi, Francesco; Arbitrio, Mariamena; Pioli, Claudio; Poccia, Fabrizio; Cicconi, Rosella; Doria, Gino

doi:10.1038/sj.bmt.1702169

Cited by 27 publications

(17 citation statements)

References 21 publications

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“…Additionally, we used CD45.1 recipients to unambiguously quantify the contribution from aneuploid and euploid wild-type littermate donors. We further note that, in this experimental setup, a small population of recipient-derived memory T cells remains in the recipient peripheral blood after reconstitution despite lethal irradiation (Frasca et al 2000). This recipientderived memory cell population is evident in our data 3 wk after transfer ( Fig.…”

Section: Aneuploidy Decreases Hsc Competitive Fitness In Vivosupporting

confidence: 54%

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

et al. 2016

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Aneuploidy, an imbalanced karyotype, is a widely observed feature of cancer cells that has long been hypothesized to promote tumorigenesis. Here we evaluate the fitness of cells with constitutional trisomy or chromosomal instability (CIN) in vivo using hematopoietic reconstitution experiments. We did not observe cancer but instead found that aneuploid hematopoietic stem cells (HSCs) exhibit decreased fitness. This reduced fitness is due at least in part to the decreased proliferative potential of aneuploid hematopoietic cells. Analyses of mice with CIN caused by a hypomorphic mutation in the gene Bub1b further support the finding that aneuploidy impairs cell proliferation in vivo. Whereas nonregenerating adult tissues are highly aneuploid in these mice, HSCs and other regenerative adult tissues are largely euploid. These findings indicate that, in vivo, mechanisms exist to select against aneuploid cells.

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Section: Aneuploidy Decreases Hsc Competitive Fitness In Vivosupporting

confidence: 54%

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

et al. 2016

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“…Recipient female ROSA26 mice (5-7 weeks) were irradiated with two doses of 549 rads, enough for a lethal dose (Frasca et al, 2000), given ~3 hours apart (Uchida et al, 1994) using a Gammacel irradiator (Atomic Energy of Canada Ltd) prior to transplantation with either WBM or SP cells. 10ϫ10 6 WBM cells or 300-500 SP cells were isolated from GFP + mice, resuspended in 150 μl of sterile PBS and injected into the tail vein of restrained mice using an insulin syringe.…”

Section: Bone Marrow Transplantation and Muscle Damagementioning

confidence: 99%

Bone marrow side population cells are enriched for progenitors capable of myogenic differentiation

Luth

Jun

Wessen

et al. 2008

Journal of Cell Science

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Although the contribution of bone marrow-derived cells to regenerating skeletal muscle has been repeatedly documented, there remains considerable debate as to whether this incorporation is exclusively a result of inflammatory cell fusion to regenerating myofibers or whether certain populations of bone marrow-derived cells have the capacity to differentiate into muscle. The present study uses a dual-marker approach in which GFP+ cells were intravenously transplanted into lethally irradiated β-galactosidase+ recipients to allow for simple determination of donor and host contribution to the muscle. FACS analysis of cardiotoxin-damaged muscle revealed that CD45+ bone-marrow side-population (SP) cells, a group enriched in hematopoietic stem cells, can give rise to CD45–/Sca-1+/desmin+ cells capable of myogenic differentiation. Moreover, after immunohistochemical examination of the muscles of both SP- and whole bone marrow-transplanted animals, we noted the presence of myofibers composed only of bone marrow-derived cells. Our findings suggest that a subpopulation of bone marrow SP cells contains precursor cells whose progeny have the potential to differentiate towards a muscle lineage and are capable of de novo myogenesis following transplantation and initiation of muscle repair via chemical damage.

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“…The effects include alterations in cell number, leukocyte subpopulation frequencies, cytokine production, and antibody production. While the large majority of these results were obtained exposing cells and animals to X or  rays, data on the effects of exposure to protons are still limited [2][3][4][5][6][7]. Weakening of the immune system might represent a serious threat for astronauts as it could expose them not only to the action of genuine pathogens but it could also allow the opportunistic pathogens or latent virus to infect the host.…”

Section: Introductionmentioning

confidence: 99%

Effects of in Vivo Proton Irradiation on Mouse T and B Lymphocytes

Novelli¹,

Vadrucci²,

Rosado³

et al. 2017

RadJ

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Abstract. One of the major problems derived from the exposure to ionizing radiation is the impairment of the immune system. The consequent immune-depression increases the risk of infections and may lead to immunemediated disorders. The intensity and duration of the immune-compromised phase and its recovery depend on the dose, dose-rate and quality of radiation. In recent years, there has been a great interest in the effects induced by protons, both for a better assessment of the health risks in astronauts exposed to solar wind and cosmic radiations and for a better understanding of their effects in radiotherapy for oncologic patients. In the present study, we investigated the effects of the in vivo exposure to 2 Gy of integral dose absorbed by medium energy proton beams on mouse lymphoid spleen cells. The TOP-IMPLART accelerator was used as proton source. Irradiations were performed in air with pulsed (3.4 s, 10Hz) 27 MeV proton beams. During the exposure, mice were anesthetized in order to keep them in the right position. Sham-exposed anesthetized age/gender/strain-matched mice were used as controls. Twenty-four hours and 1 week after irradiation, each mouse was individually analyzed for several parameters (5 mice/group). Results showed that the number of nucleated cells in the spleen was not significantly affected. Flow cytometry analyses revealed that the percentages of helper T (CD4), cytotoxic T (CD8) and B (CD19) cells within the spleen lymphocytes were not altered 24 hours after the exposure. At variance, 1 week after the exposure the frequency of CD4 (14% vs. 9%) and CD19 (37% vs. 26%) cells reduced. Spleen cells were stimulated with an anti-CD3 antibody and LPS to induce T cell and B cell activation, respectively. Both T and B cells were functionally impaired by the exposure. Twenty-four hours after irradiation, T cell proliferation was indeed reduced by 50% in exposed mice compared with controls. B cells also displayed a reduced cell proliferation in response to the mitogenic stimulus (-33%). Interestingly, 1 week after irradiation proliferative responses of T and B cells were still compromised. This first study allowed the conclusion that, in vivo local exposure to protons induced small changes in total spleen cell number, the frequency of CD4 and B cells being reduced 1 week after the exposure. More interesting, functional responses, such as T and B cell proliferation were partially compromised. These effects, in spite of the limited area of exposure, were not recovered after 1 week.

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Hematopoietic reconstitution after lethal irradiation and bone marrow transplantation: effects of different hematopoietic cytokines on the recovery of thymus, spleen and blood cells

Cited by 27 publications

References 21 publications

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

Bone marrow side population cells are enriched for progenitors capable of myogenic differentiation

Effects of in Vivo Proton Irradiation on Mouse T and B Lymphocytes

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