Wednesday, October 28, 2015
Amniotic Fluid: New Source for Stem Cell Research
Introduction:
In the research paper, "Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research?" (link is located at the bottom of this article), scientists try to use amniotic fluid of a pregnant woman as a new source of stem cell research while avoiding the ethical concerns that usually overwhelms such studies. (A)
This study investigated whether cells that express transcription factor Oct-4 are within the amniotic fluid. The embryonology of all three germ layers exist in this very fluid including different subsets of specific cells that still need clarification. (A)There are many scientists and researchers alike whose passion resides in stem cell research where they can discover new sources of stem cells. The maintenance of Oct-4 is very important to stem cells. Each mammalian pluripotent stem cell expresses within their line the Oct-4 gene, which rapidly disappears once the cells differentiate. (A)
Samples of amniotic fluid were taken from amniocentesis which is performed after the 14th week of pregnancy during routine prenatal diagnosis. Through this process, advanced maternal age and cytogenic analyses showed normal karyotypes. (A)
In routine prenatal genetic diagnosis, a wide range of fetal abnormalities which are caused by genetic alterations, are typically discovered by doctors of the patient. Therefore, the major focus was in finding new sources of pluripotent stem cells. Here, Oct-4 acts as a marker for these very pluripotent stem cells which are expressed in embryonic carcinoma cells, embryonic stem cells, as well as embryonic germ cells. (A)
Research:
First the cells of the amniotic fluid were tested for mRNA expression of Oct-4. Along with Oct-4, stem cell factors yimentin and alkaline phosphatases through the RT+/- PCR technique were analyzed. Western blot analysis and immunocytochemistry were both used in the investigation of protein expression of Oct-4. The Oct-4-positive cells were analyzed through double immunostaining for the expression of cyclin A. (A)Results:
The techniques that were used in this study were RT+/- PCR, Western Blot, and Immunocytochemical analyzes in order to show if in the human amniotic fluid the Oct-4- negative cells first could be found which are expresed in the nucleus. The Oct-4-positive cell samples from the amniotic fluid also expressed stem cell factors (i.e. yimentin and alkaline phosphatase mRNA). Cyclin A expression showed that these positive cells are actively dividing in the amniotic fluid.Subsequently, these test results show that the amniotic fluid formed within the human body when a woman is pregnant can be a new source for isolating the Oct-4-positive stem cells (discussed above) avoiding ethical concerns that typically surround human embryonic research or studies. (A)
Links:
(A)http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.324.6616&rep=rep1&type=pdf
*These images do not belong to me- they were found on various tumblr sites! Please let me know if any are yours and I will happily give you credit for them. Thanks so much~
Tuesday, October 27, 2015
Man Made Blood
According to British authorities, 'man-made blood' will be available to be transfused into humans in the next two years. Research assistant director, Dr. Nicholas Watkins, who specializes in NHS blood and transplant research and development states that the intention behind such research is to offer specific patient groups special treatment according to their disease, illness, etc. It is NOT for the intention to replace human donation. Scientists across the globe have been investigating for a number of
years how to manufacture red blood cells to offer an alternative to
donated blood to treat patients," he said. "We are confident that by 2017 our team will be ready to carry out the first early phase clinical trials in human volunteers. These trials will compare manufactured cells with donated blood.
Continued investment in research and development is critical to our role
in saving and improving lives through blood and organ donation." (A)
Scary Decline in Blood Donations:
Research Conducted:
Blood making or hematopoietic stem cells give birth to every cell circulating in your blood system whether they are RBCs, WBCs, or platelets. These stem cells contain within them the secret to stress, old age, and disease. The fates of these unspecialized cells occur in the bone marrow and shape blood production. The bone marrow is where the hematopoietic stem cells decide what type of blood cells need to be made before being released into circulation. (B)
Emmanuelle Passegué's work on rejuvination and longer life span stems from her passion of studying blood. Eager to find out through her research how we age and our body's response to diseases. Her primary goal is to develop effective remedies for blood diseases such as leukemia, lymphoma, bone marrow failures, and anemia.
Recently, her interest in blood and her focus soon became 'how aging affects hematopoietic stem cells'. There are only a certain number of hematopoietic stem cells that we are born with and because these stem cells age with us, there will be only a few remaining hematopoietic stem cells that will still function properly. Subsequently, this leaves our bodies increasingly vulnerable to various infections, blood diseases, and fatal illnesses.(B)
In their paper, Cell Stem Cell', Passegue and her UCSF lab team described that if the causes of the decline in functionality which is heavy
age-related can be understood, then the possibility to rejuvenate the
older stem cells so that the health of the entire blood system can be
maintained then the possibility of a longer life is possible. (B)
Other researchers, besides Passque and her UCSF lab team, are
investigating the use of adult stem cells and blood from umbilical cord
as alternatives for blood donation, specifically those with complex
blood types who have a difficult time finding compatible donors so that
the body does not reject the donation. (A)
Biomedical engineers from the human bone marrow have produced functional blood platelets, also known as the cells within our circulatory system that causes clots to form, within the lab. This first step, is bringing researchers and scientists closer to man-made blood transfusions. This type of transfusion has only been tested on lab mice. The NHS Blood and Transport is one of eight goals of
the 2020 Research and Development program that aims to develop
transfusion, transplantation and regenerative medicine over the next
five years. (A) Recent
research program lead by Bristol, Cambridge, and Oxford Universities,
are dedicated to patients with sickle cell anemia and thalassemia who
need regular blood transfusions with their treatments. (A)
Links:
(A)http://www.telegraph.co.uk/news/nhs/11697294/Blood-made-in-the-lab-will-be-given-to-humans-in-two-years.html
(B)https://www.ucsf.edu/news/2015/08/131406/emmanuelle-passegue-making-better-blood
*These images do not belong to me- they were found on various tumblr sites! If any are yours please let me know and I will give you credit for them! Thanks so much!*
Friday, October 23, 2015
Undertanding the Human Body in real 3D
Some of the topics on the website include:
The Skeleton
The Heart & Circulatory System
Anatomy & Physiology
Anatomy & Function
Physiological Animations
.. and really so much more!
Thursday, October 22, 2015
2015 Nobel Prize Winners: Lindahl, Sancar, and Modrich
Göran K Hansson,
the secretary general of the Royal Swedish Academy of Sciences said: “This
year’s prize is about the cell’s tool box for repairing DNA.” Together, the
repair mechanisms discovered by Lindahl, Sancar and Modrich fix thousands of
DNA faults caused by UV rays, cigarette smoke, and other toxic substances. They
are constantly at work to repair copying errors as cells divide. Without these
repair mechanisms, the genomes would be riddled with errors, and cancer would
be rife. (A)
PROCESS:
Lindahl,
Modrich, and Sancar were honored for mapping and explaining how cells repair
their DNA and safeguard genetic information. They worked out how cells repair
faults that inevitably occur when DNA is copied several times allowing for
mutations to arise under a wide variety of environmental factors such as UV
rays in sunlight that could inevitably result in skin cancer.
Lindahl searched
for enzymes that would repair faulty genetic material, focusing on the
weaknesses of the DNA letters paired up. Cytosine pairs only with Guanine,
however when Cytosine loses an amino group- it pairs up with Adenine instead.
This error in pairing in the stands cultivates a mutation the next time it is
copied. He realized that cells MUST have a way to protect themselves from this
and in 1974 Lindahl published the details of the enzyme responsible. (A)
Aziz Sancar
Born: 1946, Savur, Turkey
Affiliation at the time of the award: University of
North Carolina, Chapel Hill, NC, USA
Prize motivation: "for mechanistic studies of
DNA repair"
Prize share: 1/3
Paul Modrich
Born: 1946
Affiliation at the time of the award: Howard Hughes
Medical Institute, Durham, NC, USA, Duke University School of Medicine, Durham,
NC, USA
Prize motivation: "for mechanistic studies of
DNA repair"
Prize share: 1/3
Tomas Lindahl
Born: 1938, Stockholm, Sweden
Affiliation at the time of the award: Francis Crick
Institute, Hertfordshire, United Kingdom, Clare Hall Laboratory, Hertfordshire,
United Kingdom
Prize motivation: "for mechanistic studies of
DNA repair"
Prize share: 1/3
CONCLUSION:
The committee
stated that, “Their systematic work has made a decisive contribution to the
understanding of how the living cell functions, as well as providing knowledge
about the molecular causes of several hereditary diseases and about mechanisms
behind both cancer development and ageing,” adding, “All chemical
processes are prone to random errors. Additionally, your DNA is subjected on a
daily basis to damaging radiation and reactive molecules. In fact, you ought to
have been a chemical chaos long before you even developed into a foetus."
(A)
LINKS:
(A)
http://www.theguardian.com/science/2015/oct/07/lindahl-modrich-and-sancar-win-nobel-chemistry-prize-for-dna-research
(B)
nobelprize.org
Turning Leukemia Cells on themselves: Mission Accomplished
What are Leukemia Cells?
Leukemia is by definition a malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leukocytes. These suppress the production of normal blood cells, leading to anemia and other symptoms. This disease is very difficult to treat because the leukemia cells (which are cancer cells) affect the bone marrow and the RBCs have the tendency to relapse and resist treatment.Cancer Research (Introduction) :
A major goal in cancer research is to discover agents that transform malignant cells into benign cells. The process in which researchers and scientists approach cancer therapy involves finding agents that have the ability to change the state of differentiation of cancer cells. In a recently discovered phenomenon 'receptor pleiotropism' conversion of acute myeloblastic leukemia cells into natural killer cells is very possible. (Receptor Pleiotropism is when agonist antibodies are against known receptors which induce the cell fates that are very different from those that are induced by the natural agonist to the same receptor.) (A)In a recent new study, performed by scientists of the Scripps Research Institute, discovered an extremely rare human antibody that makes leukemia cells kill each other. The leukemia cells are convinced to transform into leukemia-killing immune cells, in which their biological programming has been rewritten. Antibody therapies has long been the main goal of many scientists as they have been trying to treat individuals whose bone marrow does not produce enough WBCs (aka: immune cell deficiency). Finding antibodies that could activate receptors on the immature bone marrow cells that would cause them to change into mature cells was the mission. (B)
When introduced to the antibody the leukemia cells enter a differentiation cascade where 80% of the starting leukemic cells can be differentiated. The antibody-induced killer cells make large amounts of perforin, IFN-γ, and granzyme B which attack, subsequently killing other members of the leukemic cell population. (A) It is important to note that induction of killer cells is confined to transformed cells because the normal bone marrow cells are not induced to form killer cells. It is therefore very possible to use agonist antibodies to change the differentiation state of cancer cells into those that attack and kill other members of malignant clone from which they originate. (A)
Those who suffered from AML (Acute Myeloid Leukemia) produce too many WBCs in their bone marrow interfering with the normal production of other blood cell types. This aggressive type of leukemia attacks the myeloid cells in the body that deal with bacterial infections, parasites, and prevent the spread of tissue damage. (B)
Concluding Results:
When researchers decided to flood the human blood sample with AML cells (including the growth activating antibodies) the results were astonishing as these very same antibodies transformed the AML cells into dendrite cells. (Dendrite cells support the immune system) With extended exposure to these antibodies, the cells matured further into natural killer cells that behave similarly to cells that kill threats to the human body such as viruses, bacteria, and cancer cells. These NK cells destroyed 15% of the cancerous cells in a single day. However, these NK cells only seem to target their former AML cell type, not other types of cancer cells.(B) Future Goals: The finding that agonist antibody converts leukemic cells into killer cells could be the key to treating or even healing patients diagnosed with cancer. Along with the transformation of cancer cells into less aggressive form, cells that have been recently induced have within them a killer phenotype as they kill other unconverted members of the malignant clone. (A) Researchers aim to use this technique that they call the 'Fraticidin Therapy' to transform a range of cancer cells into specific NK cells to cure a cancer patient all together. (B)
Links:
(A) http://www.pnas.org/content/early/2015/10/20/1519079112
(B)http://www.iflscience.com/health-and-medicine/scientists-can-now-make-leukemia-cells-kill-each-other
Tuesday, October 20, 2015
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