Extensive studies of mice deficient in one or several cytokine receptors have failed to support an indispensable role of cytokines in development of multiple blood cell lineages. Whereas B1 B cells and Igs are sustained at normal levels throughout life of mice deficient in IL-7, IL-7Ralpha, common cytokine receptor gamma chain, or flt3 ligand (FL), we report here that adult mice double deficient in IL-7Ralpha and FL completely lack visible LNs, conventional IgM+ B cells, IgA+ plasma cells, and B1 cells, and consequently produce no Igs. All stages of committed B cell progenitors are undetectable in FL-/- x IL-7Ralpha-/- BM that also lacks expression of the B cell commitment factor Pax5 and its direct target genes. Furthermore, in contrast to IL-7Ralpha-/- mice, FL-/- x IL-7Ralpha-/- mice also lack mature B cells and detectable committed B cell progenitors during fetal development. Thus, signaling through the cytokine tyrosine kinase receptor flt3 and IL-7Ralpha are indispensable for fetal and adult B cell development.
For more information please click here.
Saturday 27 March 2010
Interleukin-3 supports expansion of long-term multilineage repopulating activity after multiple stem cell divisions in vitro
David Bryder and Sten E. W. Jacobsen
Although long-term repopulating hematopoietic stem cells (HSC) can self-renew and expand extensively in vivo, most efforts at expanding HSC in vitro have proved unsuccessful and have frequently resulted in compromised rather than improved HSC grafts. This has triggered the search for the optimal combination of cytokines for HSC expansion. Through such studies, c-kit ligand (KL), flt3 ligand (FL), thrombopoietin, and IL-11 have emerged as likely positive regulators of HSC self-renewal. In contrast, numerous studies have implicated a unique and potent negative regulatory role of IL-3, suggesting perhaps distinct regulation of HSC fate by different cytokines. However, the interpretations of these findings are complicated by the fact that different cytokines might target distinct subpopulations within the HSC compartment and by the lack of evidence for HSC undergoing self-renewal. Here, in the presence of KL+FL+megakaryocyte growth and development factor (MGDF), which recruits virtually all LinSca-1+kit+ bone marrow cells into proliferation and promotes their self-renewal under serum-free conditions, IL-3 and IL-11 revealed an indistinguishable ability to further enhance proliferation. Surprisingly, and similar to IL-11, IL-3 supported KL+FL+MGDF-induced expansion of multilineage, long-term reconstituting activity in primary and secondary recipients. Furthermore, high-resolution cell division tracking demonstrated that all HSC underwent a minimum of 5 cell divisions, suggesting that long-term repopulating HSC are not compromised by IL-3 stimulation after multiple cell divisions. In striking contrast, the ex vivo expansion of murine HSC in fetal calf serum-containing medium resulted in extensive loss of reconstituting activity, an effect further facilitated by the presence of IL-3. (Blood. 2000;96:1748-1755)
To read the whole article please click here.
Although long-term repopulating hematopoietic stem cells (HSC) can self-renew and expand extensively in vivo, most efforts at expanding HSC in vitro have proved unsuccessful and have frequently resulted in compromised rather than improved HSC grafts. This has triggered the search for the optimal combination of cytokines for HSC expansion. Through such studies, c-kit ligand (KL), flt3 ligand (FL), thrombopoietin, and IL-11 have emerged as likely positive regulators of HSC self-renewal. In contrast, numerous studies have implicated a unique and potent negative regulatory role of IL-3, suggesting perhaps distinct regulation of HSC fate by different cytokines. However, the interpretations of these findings are complicated by the fact that different cytokines might target distinct subpopulations within the HSC compartment and by the lack of evidence for HSC undergoing self-renewal. Here, in the presence of KL+FL+megakaryocyte growth and development factor (MGDF), which recruits virtually all LinSca-1+kit+ bone marrow cells into proliferation and promotes their self-renewal under serum-free conditions, IL-3 and IL-11 revealed an indistinguishable ability to further enhance proliferation. Surprisingly, and similar to IL-11, IL-3 supported KL+FL+MGDF-induced expansion of multilineage, long-term reconstituting activity in primary and secondary recipients. Furthermore, high-resolution cell division tracking demonstrated that all HSC underwent a minimum of 5 cell divisions, suggesting that long-term repopulating HSC are not compromised by IL-3 stimulation after multiple cell divisions. In striking contrast, the ex vivo expansion of murine HSC in fetal calf serum-containing medium resulted in extensive loss of reconstituting activity, an effect further facilitated by the presence of IL-3. (Blood. 2000;96:1748-1755)
To read the whole article please click here.
Why study?
The more I study.
The more I know.
The more I know.
The more I forget.
The more I forget.
The less I know.
So why study?
The more I know.
The more I know.
The more I forget.
The more I forget.
The less I know.
So why study?
Thursday 18 March 2010
Trofim Denisovich Lysenko - fraudulent of science
(Russian: Трофи́м Дени́сович Лысе́нко, Ukrainian: Трохим Денисович Лисенко, Trofym Denysovych Lysenko)
(September 29, 1898 – November 20, 1976) was a Ukrainian agronomist who was director of Soviet biology
under Joseph Stalin. Lysenko rejected Mendelian genetics in favor of the hybridization theories of Russian
horticulturist Ivan Vladimirovich Michurin, and adopted them into a powerful political-scientific movement
termed Lysenkoism. His unorthodox experimental research in improved crop yields earned the support of Soviet
leader Joseph Stalin, especially following the famine and loss of productivity resulting from forced collectivization
in several regions of the Soviet Union in the early 1930s. In 1940 he became director of the Institute of Genetics within
the USSR's Academy of Sciences, and Lysenko's anti-Mendelian doctrines were further secured in Soviet science and education
by the exercise of political influence and power. Scientific dissent from Lysenko's theories of environmentally acquired
inheritance was formally outlawed in 1948, and for the next several years opponents were purged from held positions, and
many imprisoned. Lysenko's work was officially discredited in the Soviet Union in 1964, leading to a renewed emphasis
there to re-institute Mendelian genetics and orthodox science.Though Lysenko remained at his post in the Institute of Genetics until 1965,[1] his influence on Soviet agricultural practice declined by the 1950s.
The Soviet Union quietly abandoned Lysenko's agricultural practices in favor of modern agricultural practices after the crop yields he promised failed to materialize. Today much of Lysenko's agricultural experimentation
and research is largely viewed as fraudulent.
(September 29, 1898 – November 20, 1976) was a Ukrainian agronomist who was director of Soviet biology
under Joseph Stalin. Lysenko rejected Mendelian genetics in favor of the hybridization theories of Russian
horticulturist Ivan Vladimirovich Michurin, and adopted them into a powerful political-scientific movement
termed Lysenkoism. His unorthodox experimental research in improved crop yields earned the support of Soviet
leader Joseph Stalin, especially following the famine and loss of productivity resulting from forced collectivization
in several regions of the Soviet Union in the early 1930s. In 1940 he became director of the Institute of Genetics within
the USSR's Academy of Sciences, and Lysenko's anti-Mendelian doctrines were further secured in Soviet science and education
by the exercise of political influence and power. Scientific dissent from Lysenko's theories of environmentally acquired
inheritance was formally outlawed in 1948, and for the next several years opponents were purged from held positions, and
many imprisoned. Lysenko's work was officially discredited in the Soviet Union in 1964, leading to a renewed emphasis
there to re-institute Mendelian genetics and orthodox science.Though Lysenko remained at his post in the Institute of Genetics until 1965,[1] his influence on Soviet agricultural practice declined by the 1950s.
The Soviet Union quietly abandoned Lysenko's agricultural practices in favor of modern agricultural practices after the crop yields he promised failed to materialize. Today much of Lysenko's agricultural experimentation
and research is largely viewed as fraudulent.
Thursday 11 March 2010
Norman Bethune
Henry Norman Bethune (March 3, 1890 – November 12, 1939; Chinese name: 白求恩; pinyin: Bái Qiúēn) was a Canadian physician and medical innovator. Bethune is best known for his service in war time medical units during the Spanish Civil War and with the Chinese Armies during the Second Sino-Japanese War. He developed the first mobile blood-transfusion service in Spain in 1936
Tuesday 2 March 2010
Biological properties and enucleation of red blood cells from human embryonic stem cells
Human erythropoiesis is a complex multistep process that involves the differentiation of early erythroid progenitors to mature erythrocytes. Here we show that it is feasible to differentiate and mature human embryonic stem cells (hESCs) into functional oxygen-carrying erythrocytes on a large scale (1010 to 1011 cells/six-well plate hESCs). We also show for the first time that the oxygen equilibrium curves of the hESC-derived cells are comparable to normal red blood cells (RBCs) and respond to changes in pH and 2,3-diphosphoglyerate. Although these cells mainly expressed fetal and embryonic globins, they also possessed the capacity to express the adult definitive -globin chain upon further maturation in vitro. PCR and globin chain specific immunofluorescent analysis showed that the cells increased expression of -globin (increased from 0% to over 16%) after in vitro culture. Importantly, the cells underwent multiple maturation events, including a progressive decrease in size, increase in glycophorin A expression, and chromatin and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to over 60% of the cells generating RBCs with a diameter of approximately 6-8 µm. The results show that it is feasible to differentiate and mature hESCs into functional oxygen-carrying erythrocytes on a large scale
Artificial blood from stem cell
Blood donations may become a thing of the past due to advances in stem cell technology, newspapers report. The Daily Telegraph says that a new way has been discovered of growing “potentially unlimited supplies of blood in the lab”. Researchers in the USA have found that human embryonic stem cells – cells that can mature into a variety of cells in the body – can be turned into oxygen-carrying red blood cells.
This is laboratory research and it is still at an early stage. Although the findings show great potential, further work will be needed to explore the applications, drawbacks and safety issues of the technique before it could reach a stage where it would be possible to transplant these manufactured blood cells into a live recipient. For the foreseeable future, there will be no change to the current system of reliance upon blood donation, and hospital blood banks remain in great need of donated blood to meet constant demands.
Where did the story come from?
Shi-Jiang Lu and colleagues from Advanced Cell Technology, University of Illinois at Chicago, and the Mayo Clinic, US, carried out this research. No sources of funding are reported for this research. It was published in the peer-reviewed medical journal: Blood.
What kind of scientific study was this?
This was a laboratory study designed to demonstrate that it is possible for human embryonic stem cells to be formed and matured into oxygen-carrying red blood cells (erythrocytes) and produced on a large scale.
The researchers used four different stem cell lines (reported by code names in the journal paper) and a complex three-week laboratory procedure involving four stages to generate and mature red blood cells. The stages involved forming the red blood cell line from the undifferentiated stem cells, forming and expanding blast cells from which the red cells would develop, differentiating the blast cells into red cells and then “enriching” the red cells.
The resulting red blood cells were washed in an antibody mixture and stained so that the researchers could examine the cell structure. Another laboratory method was used to assess the capacity for the cells to carry oxygen. The red blood cells were also assessed for their characteristic “blood type”, by looking for A or B and rhesus antigen markers on the cell surface (“O” type blood – rhesus negative cells without A, B or rhesus antigens – are ideal, as these can be transfused into people with any blood type).
What were the results of the study?
The researchers found that, on examination, the cells produced still expressed foetal and embryonic structures; however, after maturation they also expressed a particular structure (a beta-globin chain) which is a feature of red blood cells in adults. After culture in the lab, expression of this chain increased from 0% to over 16%.
"We have developed a reproducible system to generate erythroid cells with oxygen carrying ability"Shi-Jiang Lu, lead author
The cells also underwent structural and nucleic changes which made them more like red blood cells, with an abundance of haemoglobin (the molecule that carries oxygen in red blood cells) found in the cytoplasm of the cell. However, the cells were larger than normal, with a greater diameter. The cells were found to have an oxygen-carrying capacity which was similar to normal red blood cells; they also responded to changes in acidity in a similar way. The blood type – determined by A, B and rhesus antigen expression on the cells – differed depending on which stem cell line they had come from.
What interpretations did the researchers draw from these results?
The researchers conclude that it is possible for human embryonic stem cells to be formed and matured into oxygen-carrying red blood cells (erythrocytes) and produced on a large scale. Therefore, there is the potential for developing an “inexhaustible and donorless source of cells for human therapy”.
What does the NHS Knowledge Service make of this study?
This study has provided an initial demonstration of a system by which large numbers of functional oxygen-carrying red blood cells could be developed from human embryonic stem cell lines. However, the research is still at an early stage. Although the findings show great potential, further work will be needed to investigate the applications, drawbacks and safety issues of the technique before it could reach a stage where it were possible to transplant these manufactured blood cells into a live recipient. For the foreseeable future there will be no change to the current system of reliance upon blood donation, and hospital blood banks remain greatly in need of donated blood to meet constant demands.
This is laboratory research and it is still at an early stage. Although the findings show great potential, further work will be needed to explore the applications, drawbacks and safety issues of the technique before it could reach a stage where it would be possible to transplant these manufactured blood cells into a live recipient. For the foreseeable future, there will be no change to the current system of reliance upon blood donation, and hospital blood banks remain in great need of donated blood to meet constant demands.
Where did the story come from?
Shi-Jiang Lu and colleagues from Advanced Cell Technology, University of Illinois at Chicago, and the Mayo Clinic, US, carried out this research. No sources of funding are reported for this research. It was published in the peer-reviewed medical journal: Blood.
What kind of scientific study was this?
This was a laboratory study designed to demonstrate that it is possible for human embryonic stem cells to be formed and matured into oxygen-carrying red blood cells (erythrocytes) and produced on a large scale.
The researchers used four different stem cell lines (reported by code names in the journal paper) and a complex three-week laboratory procedure involving four stages to generate and mature red blood cells. The stages involved forming the red blood cell line from the undifferentiated stem cells, forming and expanding blast cells from which the red cells would develop, differentiating the blast cells into red cells and then “enriching” the red cells.
The resulting red blood cells were washed in an antibody mixture and stained so that the researchers could examine the cell structure. Another laboratory method was used to assess the capacity for the cells to carry oxygen. The red blood cells were also assessed for their characteristic “blood type”, by looking for A or B and rhesus antigen markers on the cell surface (“O” type blood – rhesus negative cells without A, B or rhesus antigens – are ideal, as these can be transfused into people with any blood type).
What were the results of the study?
The researchers found that, on examination, the cells produced still expressed foetal and embryonic structures; however, after maturation they also expressed a particular structure (a beta-globin chain) which is a feature of red blood cells in adults. After culture in the lab, expression of this chain increased from 0% to over 16%.
"We have developed a reproducible system to generate erythroid cells with oxygen carrying ability"Shi-Jiang Lu, lead author
The cells also underwent structural and nucleic changes which made them more like red blood cells, with an abundance of haemoglobin (the molecule that carries oxygen in red blood cells) found in the cytoplasm of the cell. However, the cells were larger than normal, with a greater diameter. The cells were found to have an oxygen-carrying capacity which was similar to normal red blood cells; they also responded to changes in acidity in a similar way. The blood type – determined by A, B and rhesus antigen expression on the cells – differed depending on which stem cell line they had come from.
What interpretations did the researchers draw from these results?
The researchers conclude that it is possible for human embryonic stem cells to be formed and matured into oxygen-carrying red blood cells (erythrocytes) and produced on a large scale. Therefore, there is the potential for developing an “inexhaustible and donorless source of cells for human therapy”.
What does the NHS Knowledge Service make of this study?
This study has provided an initial demonstration of a system by which large numbers of functional oxygen-carrying red blood cells could be developed from human embryonic stem cell lines. However, the research is still at an early stage. Although the findings show great potential, further work will be needed to investigate the applications, drawbacks and safety issues of the technique before it could reach a stage where it were possible to transplant these manufactured blood cells into a live recipient. For the foreseeable future there will be no change to the current system of reliance upon blood donation, and hospital blood banks remain greatly in need of donated blood to meet constant demands.
Subscribe to:
Posts (Atom)
