Changes in the hemopoietic system of mice deficient for tumor necrosis factor or lymphotoxin-α

Drize, Nina; Drutskaya, Marina S.; Герасимова, Л. П.; Манакова, Т. Е.; Chertkov, I. L.; Turetskaya, Regina L.; Kuprash, Dmitry V.; Nedospasov, Sergei A.

doi:10.1007/bf02682103

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…This was further supported in vitro in TNF-deficient long-term bone marrow cultures, which were characterized by increased proliferative potential of granulocytic progenitors and increased numbers of CFU-GMs within sorted LSK population, as compared to WT BM cultures ( 19 ). Consistent with in vitro data, CFU-GM formation was reduced in WT-recipient mice reconstituted with TNF-deficient BM, suggesting a possible role of TNF, expressed by hematopoietic and not by stromal cells, in inducing cell death at the GMP stage ( 33 ). This is also in agreement with data showing elimination of GMPs by TNF in a dose-dependent manner ( 21 ).…”

Section: Tnf In Stress- and Inflammation-induced Hematopoiesissupporting

confidence: 81%

Current Perspectives on the Role of TNF in Hematopoiesis Using Mice With Humanization of TNF/LT System

et al. 2021

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TNF is a multifunctional cytokine with its key functions attributed to inflammation, secondary lymphoid tissue organogenesis and immune regulation. However, it is also a physiological regulator of hematopoiesis and is involved in development and homeostatic maintenance of various organs and tissues. Somewhat unexpectedly, the most important practical application of TNF biology in medicine is anti-TNF therapy in several autoimmune diseases. With increased number of patients undergoing treatment with TNF inhibitors and concerns regarding possible adverse effects of systemic cytokine blockade, the interest in using humanized mouse models to study the efficacy and safety of TNF-targeting biologics in vivo is justified. This Perspective discusses the main functions of TNF and its two receptors, TNFR1 and TNFR2, in steady state, as well as in emergency hematopoiesis. It also provides a comparative overview of existing mouse lines with humanization of TNF/TNFR system. These genetically engineered mice allow us to study TNF signaling cascades in the hematopoietic compartment in the context of various experimental disease models and for evaluating the effects of various human TNF inhibitors on hematopoiesis and other physiological processes.

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Section: Tnf In Stress- and Inflammation-induced Hematopoiesissupporting

confidence: 81%

Current Perspectives on the Role of TNF in Hematopoiesis Using Mice With Humanization of TNF/LT System

et al. 2021

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“…The incidence of hemopoietic precursor cells was evaluated by the count of cells forming cobblestone areas on days 7 and 28 (CAFC-7 and CAFC-28) as described previously [5], the count of granulocytic macrophagal CFU (CFU-GM) was determined by a previously described method [4], and the incidence of splenic CFU (CFU-S) by the method of Till and MacCulloch [1]. In order to evaluate the self-maintenance capacity of stromal cells released after long culturing into TNF-/-LTBMC suspension fraction, the cells of this fraction from the test cultures were inoculated into a 24-well plate (100,000 cells per well) for culturing in Fisher medium with 15% FCS and 10% WEHI 3B cell strain conditioned medium.…”

Section: Methodsmentioning

confidence: 99%

Effect of TNF Expression by Stromal Cells on Hemopoietic and Stromal Precursor Cells in Long-Term Bone Marrow Cultures Derived from TNF-Deficient Mice

Nifontova

2005

Bull Exp Biol Med

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The effect of TNF expression by wild type stromal sublayer on hemopoiesis was studied in cultures after second inoculation of TNF-deficient bone marrow cells. Long-term maintenance of hemopoiesis was determined solely by the absence of autocrine expression of TNF by hemopoietic cells. The production of hemopoietic precursors of all studied types in TNF-deficient cultures on a wild type sublayer was significantly higher than in cultures without TNF production. Presumably, initial expression of TNF in the sublayer promotes the survival of hemopoietic precursors with high proliferative potential in the culture. It is also obvious that TNF is required for normal functioning of stromal precursor cells.

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“…The functional in vitro tests showed that interaction between stromal and hemopoietic cells is disturbed in knockout mice: stromal precursor cells of mice deficient for TNF (TNF-/-mice) practically do not tolerate the microenvironment during ectopic bone marrow transplantation [1].…”

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confidence: 99%

Stromal cell strains derived from suspension fraction of bone marrow cultures of tumor necrosis factor-deficient mice

Nifontova

Olshanskaya

2004

Bull Exp Biol Med

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Culturing of suspension fraction of a long-term bone marrow culture derived from tumor necrosis factor (TNF)-deficient mice for 75 days produced cells forming adherent cell strains. The cells of all strains expressed RNA of various stromal differentiating markers in various combinations. The cells of many strains simultaneously expressed genes encoding products characteristic of different differentiation lineages. The derived strains maintained hemopoiesis for 10 weeks. RNA-analysis of gene expression by cells of these strains showed that they express a set of various growth factors and cytokines. It was hypothesized that suspension fraction of long-term bone marrow culture derived from TNF-deficient mice includes immature stromal precursor cells, which were never detected in long-term bone marrow culture derived from wild-type mice.

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Changes in the hemopoietic system of mice deficient for tumor necrosis factor or lymphotoxin-α

Cited by 6 publications

References 14 publications

Current Perspectives on the Role of TNF in Hematopoiesis Using Mice With Humanization of TNF/LT System

Current Perspectives on the Role of TNF in Hematopoiesis Using Mice With Humanization of TNF/LT System

Effect of TNF Expression by Stromal Cells on Hemopoietic and Stromal Precursor Cells in Long-Term Bone Marrow Cultures Derived from TNF-Deficient Mice

Stromal cell strains derived from suspension fraction of bone marrow cultures of tumor necrosis factor-deficient mice

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