Exercise in a Pill

July 31, 2008 -- It may be possible to make a pill that captures the endurance-boosting effects of exercise, scientists report in Cell.

So far, they've tested two compounds in lab tests in mice. One of those compounds, called GW1516, boosted endurance in mice that exercised, but not in sedentary mice. The other compound, called AICAR, improved endurance in mice that didn't exercise at all.

Those compounds haven't yet been tested in people, and they're not on the market. But the researchers are already working on a drug test to screen for traces of GW1516 and AICAR in athletes' blood and urine.

Here's a quick look at the two compounds.

Back in 2004, the researchers -- who included professor Ronald M. Evans, PhD, of the Salk Institute for Biological Studies and the Howard Hughes Medical Institute in La Jolla, Calif. -- reported that they boosted endurance in mice by tweaking a mouse gene to boost the activity of a protein called PPAR-delta.

Evans' team then worked on getting the same result without genetic engineering. They squirted GW1516, which boosts PPAR-delta, into mice's mouths every day for a month.

At the end of the month, the mice ran 68% longer and 70% farther than when the experiment began -- but only if they had been running on exercise wheels daily while taking the drug. GW1516 didn't do anything for mice that weren't exercising.

Next, the scientists focused on another protein called AMPK. They gave sedentary mice a daily injection of AICAR, which boosts AMPK, for a month.

At the end of the month, those mice ran 23% longer and 44% farther than before starting AICAR treatment. That is, their endurance had improved without working out.

The results show that AMPK and PPAR-delta "can be targeted by orally active drugs to enhance training or even to increase endurance without exercise," write the researchers.

The mouse tests were all about skeletal muscles and endurance, not about the drugs' safety or ability to mimic the many other benefits of exercise, such as improving cardiovascular health and making some types of cancer less likely.

http://www.btec.cmu.edu/tutorial/bone_tissue_engineering/bone_tissue_engineering.htm
http://www.cs.cmu.edu/~tissue/
http://www.bone-tec.com/

Bone Tissue Engineering

Bone tissue engineering is a rapidly developing area. This form of therapy differs from standard drug therapy or permanent implants in that the engineered bone becomes integrated within the patient, affording a potentially permanent and specific cure of the disease state. The problem with putting man-made materials in the body is that they are subject to fatigue, fracture, toxicity, and wear, and do not remodel with time. In tissue engineering for the bones, you make the cells in a culture and then place them into the patient. Cells in the body are constantly receiving mechanical, electrical, structural and chemical cues to what they should be doing. So it is important to place the cell in back into the body so that can get the cures so go in the shape and form that they are needed to be in. Bone tissue engineering can possibly for a substitute in the bone instead of using man made materials.

Bioengineered external heart

Earlier this year tissue engineers at the University of Minnesota have created the first externally engineered heart. They stripped a rat’s heart of its own cells using a kind of bleach solution. Afterwards they infused the adult rat heart cells with that of a newborn rat. This takes quite a bit of time and skill but many of the scientists argee that this is a landmark in the field of tissue engineering. Being able to engineer organs could one day result in the making of biocompatible transplant organs for patients. We are nowhere near this point right now but it is still a field of research that deserves much attention.
There are many challenges in created a working heart for humans in an external environment. First of all the heart muscle is very thick and tissue engineers have not found a way yet to ensure that enough oxygen gets to the inner layers of the heart muscle. That and creating the necessary scaffolding for a three dimensional structure is on the top of the list of major problems. The easiest part about the project is that for heart cells you don’t have to tell them to beat in synchrony because they already know to do that.
Many of the researchers at the University of Minnesota are very optimistic and hope to have a working human heart and hopefully other organs such kidneys, livers, and lungs. They wish to have at least a working one of these within 15 years. These are very optimistic propositions but nonetheless it has been a great achievement in the biomedical industry.
http://www.startribune.com/lifestyle/health/13751901.html

Sources and Cool Article

Here's my sources:
http://www.cbte.group.shef.ac.uk/research/te5.html
http://www.innovations-report.com/html/reports/medicine_health/report-42576.html
http://www.jhu.edu/JLAB/Projects/Cornea.html

And here's a cool article about sweat glands functioning as antennaes:
http://physicsworld.com/cws/article/news/33704
(The link may not work unless you make an account on their site)

Corneal Tissue Engineering

Due to the fragility of the eye, a 5-30% rejection rate for donor eyes, and the complexity of creating a transducer to send image data to the brain, corneal tissue engineering is a more friendly approach to a persistent problem; how to return site to those who have lost it due to disease or damage to the eye, or in this particular case, the cornea. Currently, corneal epithelial cells from other, healthy donors can be succesfully cultured and prepared for placement on the cornea. However, these donor epithelial cells are often rejected, and a patient wanting to undergo this treatment must take immunosuppressants (though in the distant future, healthy epithelial cells might be able to be genetically engineered from the patients own epithelial cells, preventing acceptance problems). There are also significant problems with attaching these epithelial cells to the damaged cornea. Currently this area is undergoing the most thorough investigation, resulting in a variety of different methods. The most common method is to use a human amniotic membrane as a hub to which all the epithelial cells can attach, and then to suture this onto the cornea. But this method requires an amniotic membrane donor, making supply and issue two major issues. There is also a proposed method of engineering a contact lense capable of transfering the epithelial cells to the damaged sections of the cornea, which requires an acrylic acid coating on the contact lense. However, engineering a suitable contact lense requires extensive knowlege of both organ culture and surface chemical engineering, making the construction a very complex process.

Tissue Engineered Bladder

For patients with bladder disease, one of the only treatment options was the replacement of bladder tissue with intestinal tissue. Side effects of that procedure include colon cancer and infection, because the intestinal tissue is designed to absorb water rather than release water. Another option is to tissue-engineer a new bladder from cells. At Wake Forest University, doctors took a biopsy of the bladder and seeded the cells into a scaffold made of synthetic polymer. The synthetic polymer scaffold is designed to fit the patient and mimic the collagen that exists in the natural bladder. After seven weeks in an incubator, the cells colonized and the bladder was implanted about the existing bladder, where it would continue to grow and improve existing bladder function. While the procedure is still experimental and cannot repair nerve damage, it tremendously improves the lives of bladder disease patients.

Sources:

http://www.washingtonpost.com/wp-dyn/content/article/2006/04/03/AR2006040301387.html

http://news.healingwell.com/index.php?p=news1&id=531931

Artificial Blood

Eric Shine
Engineering Biomedical Systems
July 31, 2008

Artificial Blood

Tissue engineering is a broad field of engineering that deals with a combination of cells, and engineering methods that are used to improve of replace biological functions. An application of tissue that could help improves or replaces biological functioning would be the creation of artificial blood. Blood is a very complicated tissue. Blood contains two main components plasma and the formed elements. To add further complexity the formed elements are made up of RBCs (red blood cells), WBCs (white blood cells), and platelets. Along with blood being the transportation system of the body, blood comes in four different types: A, B, AB, and O. Since blood Artificial blood would help traumatic brain injuries, which is a leading cause in accidental death. Even though blood is very complex engineers and scientist have made a type of artificial blood called Oxycyte. Oxycyte is a revolutionary artificial blood because it can carry 50 times more oxygen than human blood. This synthetic blood is step in making blood transfusions and other types of blood related problems a thing of the past.

http://www.popsci.com/scitech/article/2006-11/better-blood
http://health.howstuffworks.com/artificial-blood1.htm
http://en.wikipedia.org/wiki/Tissue_engineering#Examples_of_tissue_engineering_technologies

An Artificial Pancreas

Diabetes is a physically as well as mentally and emotionally devastating disease. The inability of the pancreas to efficiently produce insulin lies at the root of the diabetic problem. There are machines and pumps available today for sufferers of diabetes to track their blood glucose levels and to regulate their insulin, but the process creates constant discomfort and worry for the patient.

Tissue engineers, in their efforts, are trying to create the perfect combination of comfort and insulin production through the invention of an artificial pancreas. This artificial pancreas would be able to automatically adjust the insulin levels for a diabetic patient. It would also restore normal endocrine functionality.

The complete development and use of an artificial pancreas would improve the insulin therapy to the point at which physiological complications cease. Variations of this artificial pancreas idea have arisen among the sciences. Among them are the biomedical device ideas to implant an insulin pump that would assume the role of the pancreas, a bioartificial pancreas made of a biocompatible sheet of "encapsulated beta cells" (Wikipedia), and the use of gene therapy to convert digestive cells into insulin producing cells.

All of these projects have the common goal of creating a normal pancreas function, artificial or not, in the body. One of the benefits of tissue engineering is its more natural approach to the replacement of diseased tissues in the body.

Testing Drugs with Stem Cells

Stem cells have many applications now, and there are many more that are still being developed. However, one such use of stem cells that has already been established is the use of stem cells in testing the toxicity of pharmaceutical drugs.

Previously, drugs were tested in rats before they were administered to humans. This process is somewhat flawed in that drugs have been known to act differently in humans that in the lab animals that they were previously tested on. So, a woman named Gabriella Cezar came up with a way of using embryonic stem cells to test drug toxicity. She exposed these stem cells to the drug that was being tested and then let them react. These stem cells react with drugs like a human would, eliminating the chance of poisoning a human by accident. These stem cells produce a molecule that help metabolism. Cezar hypothesized that if the drug were toxic, then there would be different amounts of that metabolic compound in the stem cells than normally.

Cezar ran another test with valproate, a drug supposed to help and epileptic patient, which has been linked with causing autism. Cezar gave different dosages to different samples of stem cells while keeping some control groups to compare to. She found that the stem cell environments with the most valproate produced the most glutamate and kynurenin; both are used in brain development.

Even though this method of using stem cells is not an exact science yet, it is up and coming application of stem cells.

Heart in a Jar

Tissue engineering's whole purpose is to replace biological functions with new cell material products. Mostly, tissue engineers try to repair portions of organs that have been damaged. However, earlier this year, Doris Taylor made medical history by creating an entirely new rat heart in a lab. This beating heart was made by leaving only nonliving matrix of the rat's heart and redesigning it with new heart cells. To first remove all the cells to get to the matrix, detergents were pumped throughout the organ to wash away the debris in the network of blood vessels. This left the extracellular matrix or ECM as a matrix of protein fibers that create the connective tissue in the heart. This ECM was basically a skeleton of the organ's 3-D structure that was then formed into a heart with new cells. These cells were a mix of stem and progenitor cells from newborn rats that were injected into the left ventricle of the ECM. After pumping nutrients and oxygen throughout the heart and its blood vessels, four days later the heart starting contracting. The heart was then stimulated by electrodes to synchronize the beats. Taylor is continuing her study with experimenting with pig hearts and their own ECM. The hope is that one day new hearts will be creating for the 5 million people living with heart failure. This new advancement in tissue engineering could someday make organ transplants obsolete.


http://en.wikipedia.org/wiki/Doris_Taylor

http://www1.umn.edu/umnnews/Feature_Stories/Researchers_create_a_new_heart_in_the_lab.html

Gene Therapy

Gene therapy is a form of treatment that doctors and scientists hope to use against genetic diseases. Instead of battling a foreign body, which is not the source of problems in genetic diseases, the goal in gene therapy is to replace faulty genes causing illness in patients with correct ones. What one uses to replace the old gene with the new one is called a vector. There are many different vectors for placement of new genes, such as using viruses, naked-DNA injection, dendrimers, and others.

The first approved gene therapy procedure was performed in 1990. It was meant to treat severe combined immunodeficiency, or SCID, a genetic disease in which certain receptors on white blood cells are not correctly coded for in the corresponding gene, rendering white blood cells useless. Doctors removed white blood cells from the patient, a four year old girl, let the cells develop in cultures, then inserted the correct gene into the cells and put the cells back into the patient. Even though the procedure only lasted a couple months, it boosted the patient's immune system so much that she could now attend school, which she previously couldn't do due to her extremely high risk of fatal infections from what are considered mundane conditions, such as colds. This case shows promise for gene therapy, even if results aren't permanent.

http://en.wikipedia.org/wiki/Gene_therapy
http://en.wikipedia.org/wiki/Severe_combined_immunodeficiency