Histopathology of the Spleen

Suttie, Andrew W.

doi:10.1080/01926230600867750

Cited by 161 publications

(124 citation statements)

References 14 publications

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“…45,78,108,113 In mice (and, to a lesser extent, rats and hamsters), the spleen continues to play an active role in hematopoiesis throughout adulthood. 106 The shift of hematopoietic activity to spleen late in fetal development, with retention of minor residual hematopoiesis in other hemic organs (liver, lymph nodes), is consistent with the primary tissue distribution of EMH in adult animals.…”

Section: Embryonic and Fetal Blood Cell Production: Differentiation Omentioning

confidence: 64%

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

2012

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Extramedullary hematopoiesis (EMH) is the formation and development of blood cells outside the medullary spaces of the bone marrow. Although widely considered an epiphenomenon, secondary to underlying primary disease and lacking serious clinical or diagnostic implications, the presence of EMH is far from incidental on a molecular basis; rather, it reflects a well-choreographed suite of changes involving stem cells and their microenvironment (the stem cell niche). The goals of this review are to reconsider the molecular basis of EMH based on current knowledge of stem cell niches and to examine its role in the pathophysiologic mechanisms of EMH in animals. The ability of blood cells to home, proliferate, and mature in extramedullary tissues of adult animals reflects embryonic patterns of hematopoiesis and establishment or reactivation of a stem cell niche. This involves pathophysiologic alterations in hematopoietic stem cells, extracellular matrix, stromal cells, and local and systemic chemokines. Four major theories involving changes in stem cells and/or their microenvironment can explain the development of most occurrences of EMH: (1) severe bone marrow failure; (2) myelostimulation; (3) tissue inflammation, injury, and repair; and (4) abnormal chemokine production. EMH has also been reported within many types of neoplasms. Understanding the concepts and factors involved in stem cell niches enhances our understanding of the occurrence of EMH in animals and its relationship to underlying disease. In turn, a better understanding of the prevalence and distribution of EMH in animals and its molecular basis could further inform our understanding of the hematopoietic stem cell niche.

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Section: Embryonic and Fetal Blood Cell Production: Differentiation Omentioning

confidence: 64%

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

2012

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“…These are typical histopathological features of erythroid dysplasia in association with refractory anemia, a syndrome of MDS. 30 To corroborate whether the impairment resulted from an intrinsic defect in HSCs lacking IEX-1, BM cells were isolated from irradiated WT and KO mice and differentiated into myeloid progenitors in hematopoietic colony-forming culture ( Figure 7F). BM cells of irradiated KO mice showed a significant decrease in the ability to form multipotential myeloid and erythroid colonies compared to WT counterparts ( Figure 7F).…”

Section: Abnormalities In the Bm And Spleen Of Irradiated Ko Micementioning

confidence: 99%

Stress-induced hematopoietic failure in the absence of immediate early response gene X-1 (IEX-1, IER3)

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o ntributes significantly to MDS pathogenesis in these patients. The present study shows that null mutation of IEX-1 perturbs HSC quiescence and impairs maturation of platelets and red blood cells (RBCs). Upon BM transplantation or non-myeloablative radiation, changes resembling MDS occurred, including thrombocytopenia, a trend toward anemia, and granulocyte dysplasia. These observations underscore an indispensable role for IEX-1 in maintenance of HSC quiescence as well as in multiple differentiation steps along thrombopoiesis and erythropoiesis. IEX-1-deficient mice confer a novel model for investigating how mitochondrial dysfunction may cause MDS and how to prevent or slow down the disease. Methods MiceIEX-1 knockout (KO) mice on mixed 129Sv/C57BL/6 background were generated by gene-targeting deletion in our laboratory, as previously described. 17 The KO mice were bred with wild type (WT) C57BL/6 (B6) for 10 generations to obtain IEX-1 KO B6 mice. WT B6 mice and mice on 129Sv/B6 background were derived from breeding as above and used as controls. Cognate BL/6.SJL-Ptprc a Pep 3 /BoyJ (CD45.1) or PepJ mice were obtained from Jackson Laboratory. All experimental mice and BM donor mice were used at 6-8 weeks of age. Animals were maintained in the pathogen-free animal facilities of Massachusetts General Hospital in compliance with institutional guidelines. All animal studies were approved by the Subcommittee on Research Animal Care of the institute. Extended methods can be found in the Online Supplementary Appendix. Results Perturbation of HSC quiescence in the absence of IEX-1IEX-1 KO mice display no gross developmental defect except for modest hypertension at 2-months of age or older, 17,18 in agreement with its function required primarily in response to stress. Given the significant loss of IEX-1 reported in patients with early stage MDS, 14,16 we examined the status of LSK (Lineage-Sca-1 + c-Kit + ) stem cells in IEX-1 KO mice. Loss of IEX-1 led to a significant decline in the proportion of LSK cells, in comparison with WT mice (0.10±0.07% vs. 0.24±0.06 %; P<0.01) ( Figure 1A). Apparently, the decline contradicted increased cycling of the cells, as shown in Figure 1B and C, in which relatively higher proportions of KO LSK cells entered G1 and G2/S/M cycling phases than WT counterparts, concurrent with a reduced percentage of the cells at a Go or quiescent phase. We thus examined whether the decline was ascribed to increased apoptosis of the cells, because apoptosis in HSCs was abnormally high in many MDS patients. 19 Increased apoptosis of IEX-1 KO over WT BM cells was confirmed by apoptosis-specific terminal deoxynucleotydyl transferase-mediated dUTP nick end labeling or TUNEL (11.6±0.7% vs. 2.2±0.4%; P<0.01), which detected apoptosis at both early and late stages. Early apoptotic marker Annexin V staining further revealed that apoptosis was increased by more than 50% in the BM (6.9±0.5% vs. 4.5±0.3%; P<0.01) ( Figure 1D In spite of a reduced percentage of L...

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“…This result confirms that the majority of the observed microscopic findings are primarily due to spontaneous pathologic conditions. These changes are not related to specific pathogen but they could be spontaneous or secondary to opportunistic biological agents exposure not revealed by microscopic observation [28]. Furthermore, the observed mild hepatic degeneration was the most significant histological finding for both the exposed and control dams.…”

Section: Histological Findingsmentioning

confidence: 82%

The Effect of Electromagnetic Fields with the Mg<sup>2+</sup> Cyclotron Frequency on Mouse Reproductive Performance

Gerardi¹,

Ninno²,

Ferrari³

et al. 2016

JEMAA

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The present study is aimed to test whether exposure to electromagnetic fields of very weak intensity (≤1 mT) and low frequency (≤100 Hz) may influence reproductive performance and induce teratogenesis in mice. We speculate that a resonant effect occur when the applied frequency matches the cyclotron frequency of Mg 2+ (≈60 Hz) involved in the cell duplication. Four groups of mice (four dams and one male each) were exposed to ≅50 μT electromagnetic field continuous irradiation of for 100 days. A control group (four dams and one male) was also examined. The exposed dams exhibited a significantly lower number of offspring per birth than the control ones (11.0 vs. 11.6; P = 0.006). A significantly lower average daily gain of body weight per mouse was observed (0.74 vs. 0.77 g/d; P = 0.002), resulting in a reduction of the average body weight per nest at 11 days of age (404 vs. 463 g; P = 0.048). Post mortem examinations revealed a significant increase in mild chronic hepatic inflammatory findings (28 vs. 0%; P = 0.001) in the offspring and myocardial hypertrophy (25 vs. 0%; P = 0.023) in the dams. The exposure of mice to an electromagnetic field with the cyclotron frequency of Mg 2+ during pregnancy caused a measurable effect on the reproductive performance in terms of offspring per birth. This finding may be considered as a warning about the environmental effects of the electromagnetic fields on the stability of individual species and ecosystems.

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Histopathology of the Spleen

Cited by 161 publications

References 14 publications

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

Stress-induced hematopoietic failure in the absence of immediate early response gene X-1 (IEX-1, IER3)

The Effect of Electromagnetic Fields with the Mg<sup>2+</sup> Cyclotron Frequency on Mouse Reproductive Performance

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Histopathology of the Spleen

Cited by 161 publications

References 14 publications

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

Stress-induced hematopoietic failure in the absence of immediate early response gene X-1 (IEX-1, IER3)

The Effect of Electromagnetic Fields with the Mg&lt;sup&gt;2+&lt;/sup&gt; Cyclotron Frequency on Mouse Reproductive Performance

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The Effect of Electromagnetic Fields with the Mg<sup>2+</sup> Cyclotron Frequency on Mouse Reproductive Performance