Decreased Risk for Stroke with Gene Variant

For individuals who are young and middle-aged adults, cervical artery dissection exists as one of the major causes of stroke. Cervical artery dissection describes a condition where one of the arteries traveling through the neck and to the brain experiences a tear in the lining. This results in increased risk for blood clotting as well as compression of nearby nerves and blood vessels, which reduces blood flow to the brain. This decreased blood flow to the brain significantly increases the risk for an individual to experience brain damage or even a stroke, which can lead to significant mental impairment or death.

Researchers from University of London’s Royal Holloway in combination with a team of researchers spanning in geographic location from across Europe and the United States, have made a genetic discovery that explains a reduced risk in certain individuals for the aforementioned major cause of stroke. A large study was executed, including 1,400 patients with cervical artery dissection and 14,400 individuals who do not have this condition. The entire genomes of all those involved in the study were screened to determine if differences existed that would explain increased or decreased risk for cervical artery dissection. The researchers found that those with a particular gene variant, PHACTR1, had a decreased risk for being afflicted with cervical artery dissection. The gene variant has also been linked with defense against migraines and heart attack risk.

Researchers have stated that this finding will be essential in helping to further understand the impact of this particular portion of the genetic code on characteristics of blood vessel formation and maintenance in the body. They hope that such information will result in treatments and methods of prevention for conditions related to the body’s vasculature, such as stroke. They hope to do further related investigation of the genome to determine other genetic variations that may be linked to increased or decreased risk for stroke.

I find this article and the discovery it details to be very interesting. Strokes have the capability to produce such horrible brain damage and even death, so any information to further understand mechanisms that increase the likelihood of experiencing a stroke is of great value. Such information can be used for the purposes of beneficial prevention measures and treatments. It is wonderful that this study of genome screening brought light to this one particular gene variant, which decreases risk of cervical artery dissection. Hopefully, other similar findings will be made regarding other risk factors for stroke using this methodology.

Link to Article: http://www.sciencedaily.com/releases/2014/11/141125074753.htm

Related Links:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647091/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600010/

http://www.bupa.co.uk/health-information/directory/c/cervical-artery-dissection

Using Fibroblasts to Create New Blood Vessels

        Cardiovascular researchers at Houston Methodist have learned that they can use fibroblast cells and convert them into endothelial cells which will create blood vessels. Fibroblasts are the cells that cause scar tissue and are abundant in the human body. John Cooke, the study's main researcher, says that this is the first time that small molecules and proteins have been converted into a therapeutic cell type.  Cook's hope for this discovery is that it will be used to improve the healing of cardiovascular injuries and other injuries throughout the body that require an increase in circulation.There have already been studies done that use viruses to transform cells into those need in the body, but there are limitations and many risks that go along with this form of transformation. It is believed that using small molecules and proteins will be more safe for use.

The top picture shows fibroblasts stained blue, and the bottom picture shows the amount of fibroblasts that transformed into endothelial cells after treatment with poly I:C and VEGF

         The new method and Cook and his other researchers proposed involves exposing the fibroblasts to poly I:C (polyinosinic:polycytidylic acid) that will cause the cells to think that they are being attacked by a virus. Poly I:C is a small segment of RNA that binds to the host cell receptor TLR3. This viral attack caused the fibroblast cells to reorganize their nuclear chromatin, which allowed genes that had previously been blocked off to be expressed. Factors, such as VEGF, were the applied to the fibroblasts because these factors are known to cause certain cells to convert into endothelial cells. This treatment caused 2% of all the fibroblasts in the body to be transformed into endothelial cells, the same percentage outcome as using a virus to transform the cells. Cooke claims that he has unpublished work that shows that up to 15% of the fibroblasts can be converted using his method.
       
         In order to prove the effectiveness of the new cells, Cooke injected the cells into mice that had the need for new blood vessels in their hind limbs for circulation. Once the cells were introduced to the mice, the blood vessel number increased in the hind limbs and blood flow was improved. Cooke believes that his findings will pave the way for more studies to continue and possibly lead to finding ways to regenerate mass amounts of damaged tissue in humans.

       This is a very interesting study that goes to show that there are many different ways to manipulate the cells of the human body, and as our knowledge of genetics continues to grow, many more interesting findings like this will occur.

Original Article: Reprogrammed cells grow into new blood vessels

New Blood Vessels from Reprogrammed Fibroblasts

Scar cells(top) transformed into blood vessels. The
proof of transformation is indicated by the red color in
the bottom picture. The red is an indicator for CD31,
a protein made by blood vessels. 

Cardiovascular scientists from Houston Methodist, Stanford University, and Cincinnati Children’s Hospital teamed up in a joint effort to study fibroblasts, cells that cause scarring. Our bodies are filled with an immense amount of fibroblast. Through their study, the scientists discovered that the fibroblasts can be transformed into endothelium, a cell type that forms the lining of blood vessels. The method first involves polyinosinic:polycytidylic acid (poly I:C), a segment of double-stranded RNA, being introduced to fibroblasts. Poly I:C binds to TLR3(toll-like receptor 3), which fools the fibroblast cell into believing it was attacked by a virus. This resulted in a rearrangement of nuclear chromatin, which allowed genes to be expressed that were once restricted. After rearrangement, the fibroblast was treated with VEGF, Vascular endothelial growth factor, which allowed the fibroblasts to become endothelial cells.

"To our knowledge, this is the first time that trans-differentiation to a therapeutic cell type has been accomplished with a small molecules and proteins," explained chairperson, John Cooke, M.D. Houston Methodist Research Institute Department of Cardiovascular Sciences.

The next step in their research involved taking the transformed fibroblasts and introducing them to immune-deficient mice. The immune-deficient mice had poor blood circulation, however, with the transformed fibroblasts the number of vessels in the limbs of the mice increased, and ultimately improving circulation.

"The cells spontaneously form new blood vessels -- they self assemble," Cooke said. "Our transformed cells appear to form capillaries in vivo that join with the existing vessels in the animal, as we saw mouse red blood cells inside the vessels composed of human cells."

Although procedures like this have been performed, this is the first time a small molecule has been reprogrammed.  Research groups were able to generate endothelial cells from infectious viruses, viruses that were programmed to manipulate DNA cells. However, this process involves a more complicated approach. Viruses also have the potential to damage patient’s chromosomes. The small-molecule transformation of cells is a safer approach that will be utilized in clinical trials. The new research also helps our society take one step further into regenerative medicine. The new discovery will definitely help humans who suffer from poor blood circulation and cardiovascular health affects, by improving their condition through the formation of new blood vessels.

Article: http://www.sciencedaily.com/releases/2014/11/141107131658.htm

Article Related: Fibroblasts - http://ghr.nlm.nih.gov/glossary=fibroblast

A new way to monitor engineered blood vessels

Researches have found a new way to use patient's own cells to possibly cure sickle cell disease and also other diseases that are caused by mutations in hemoglobin. This new technique allows cells from a patient's skin to form iPSCs. iPSCs are capable into making different types of mature tissues and blood. This process will help repair beta-globin and aid in avoiding harmful genes. Since these iPSCs come from the patient's own body the risk of transplant reject is very small. The researchers used a two-step approach. First, they took adult skin cells from a patient with an HBB mutation that causes sickle cell disease. They used six genes to coax these cells to revert to iPSCs, which could then be developed into blood cells. The genes were introduced into the cells using a technique that avoids the use of viruses and insertion of transgenes into the cells' genome.

Self Administering Blood Vessels

Scientists have created blood vessels that reverse anemia in mice. The cells work by secreting the drug on demand, directly into the blood stream. This technology could be potentially be used to release othe proteins such as factor VIII and factor IX for pateints suffering from a multitude of different ailments. The drug secreting vessels were created by isolating an endothelial colony-forming cells to produce EPO, mesenchymal stem cells were added, suspended in a gel, and injected into the mice. The cells spontaneously formed a network of blood vessels that eventually hooked up with the animals own vessels, releasing EPO into the bloodstream. Tests showed that the drug circulating through the bloodstream was effective in treating both radiation (cancer patients) and loss of kidney tissue types of anemia. The system also had an on off switch that only released the protein when the mice were given doxycycline, if they didn't receive it EPO was not released. The system works so good because blood vessels are the one system which we can graph and have almost complete control over. Tests are underway to determine if other drugs can be administered in this manner.