Agrochemical control of plant water use via engineered abscisic acid receptors
Park et al. Nature, February 2015.

A recent breakthrough study reported that scientists successfully engineered drought-tolerant plants by adding a new piece of DNA to their genomes. Crops and many types of plants are increasingly challenged by hostile environmental conditions such as globally warming temperatures and diminishing water sources. Plants have very small openings called “stomata” that let carbon dioxide in and oxygen out. Each stoma is surrounded by two guard cells that control opening and closing using osmotic pressure. During daytime, the stomata lets plants allow carbon dioxide in and oxygen out. Since the air around the leaves is often drier than inside, water molecules also move out through the stomata – a process called transpiration. Under the stress of drought, plants produce a hormone called abscisic acid (ABA). When ABA is released, it makes guard cells close the stomata and in turn keeps the plant from losing the water. Scientists previously thought that if they could spray ABA on a whole field, plants would survive a drought. However, since ABA is very expensive and highly sensitive to light, this strategy never became an option. Then, scientists decided to take the commonly used fungicide mandipropamid and genetically engineered the plants to respond to mandipropamid as if it were ABA. By adding a new piece of DNA into genomes, plants ended up having slightly different ABA receptors, which can be efficiently activated by mandipropamid.  Researchers tried this approach on two different plants: tomatoes and Arabidopsis. When mandipropamid was sprayed, genetically engineered plants stopped transpiration, and hence were able to survive for 12 days without water. The next challenge is to test this strategy in real world crops. This approach potentially opens new avenues for crop improvement that could highly benefit a growing world population.

3D Vaccines to Cure the Cancer

Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy
Kim J et al. Nature Biotechnology, December 2014.

Cancer is a devastating disease.  The World Health Organization (WHO) predicts that global cancer incidence rates will grow by nearly 60% to 22 million cases per year over the next two decades. The effective cure for cancer has not been developed yet, mostly due to its ability to escape the body’s immune system. Unlike infectious reagents like bacteria and viruses, cancer cells are actually our own cells that are broken and misplaced; they cause trouble as they grow. Scientists have been trying hard to develop vaccines that activate the immune system to recognize tumor cells as foreign and attack them. In a recent study, scientists reported that they designed a “3D vaccine” to effectively provoke the immune system to fight cancer. The 3D vaccine is composed of many microsized, porous silica rods submersed in liquid, where any combination of tumor antigens and immune-stimulating reagents can be loaded into.  Once the 3D vaccine is injected under the skin, it forms into a dime-sized scaffold that creates an “infection-mimicking microenvironment.” The scaffold then attracts the dendritic cells that patrol the body for harmful pathogens. When the scaffold was tested in mice, it showed over a 90% survival rate in animals that would normally die from lymphoma within 25 days. Further analyses in mice showed that the 3D vaccine can recruit, house, and manipulate immune cells to initiate a powerful immune response against cancer. As much as the discovery is promising, one should keep in mind that much more evidence will be required to establish 3D vaccines as a feasible way of combating human cancer.

Smoking Shrinks the Brain

Cigarette smoking and thinning of the brain’s cortex
Karama S et al. Molecular Psychiatry, February 2015.

Smoking is regarded as the single most preventable cause of disease, disability, and death. Past studies strongly linked smoking to cancer and lung diseases. A recent study now shows that smokers have a thinner brain cortex than non-smokers. The cortex is the outer brain layer in which critical cognitive functions such as memory, language, and perception take place. It is well known that the cortex becomes thinner with normal aging and cortical thinning is associated with cognitive decline and dementia. The study found that smoking accelerates this thinning process. Researchers analyzed brain MRI scans of 244 males and 260 females with an average age of 73, around half of whom were former or current smokers. Participants who had given up smoking for the longest time had a thicker cortex compared with those who had given up recently. Researchers cautiously suggest that the cortex might regain some thickness once smokers quit but the recovery is very slow and incomplete. For example, heavy smokers who had quit more than 25 years before still had a thinner cortex.

In general, the most common approach in tissue engineering is to develop tools as needed. Physicians treat patients and define the requirements for a better cure. Then, biologists study the targeted problem and learn what the mechanism is that caused the failure. Later, chemists and materials scientists manufacture the tools needed to treat the problem. Finally, the tools are delivered to doctors to treat the patients. Thus, tissue engineering requires a good understanding of how body parts work and come into existence, and this involves precise and sensitive application. Precise, aware and regular study of the interactions involved in tissues and organs must be practiced by the researchers who are interested in developing techniques for the manufacture of potential body parts. One of the first scientific approaches used for tissue engineering is to simply inject the body with molecules, such as growth factors, which are known to promote organ formation.

The growth factors are naturally occurring proteins which are assigned for cell proliferation and differentiation. Different parts of the body require different types of growth factors to signal to the cells to multiply or to replace the cells which have died or have been damaged. For example, it has been discovered that bone morphogenic proteins are responsible for the beginning of bone cell reproduction. For someone with a fractured bone that can not heal on its own within a reasonable period of time, the injection of bone growth factors to the site can direct the body to where bone cells are needed to be produced to repair the fracture.

In more severe conditions, the body may not receive the signal only with a simple injection of the growth factors. In this case, there is a need for more intricate treatment. Another way to treat organ malfunction starts with the harvesting of cells from the patient. The harvested cells can be multiplied in an artificial scaffold to eventually be implanted into the wound site. Because cells inhabit a different world than we do, we need a way to speak their language. The artificial scaffold should provide everything a cell needs and be able to direct the targeted cells toward the desired purpose. Basic knowledge gained from biology can help us to design potential artificial environments for cells.

A critical challenge in tissue engineering is how to design and make the artificial scaffolds. The cells must be fed through the blood vessel and are grown in the scaffold by the body; the scaffold should be able to communicate with the cells and finally the scaffold should disappear when its mission has been completed. The best example of a perfect scaffold is the natural environment of the cells, the extracellular matrix (ECM). The ECM provides support and anchorage for the cells and regulates communication between cells. There are various biological signals found in the ECM that help cell survival. For example, proteins called collagens provide mechanical support for cells through adhesive proteins in the ECM and the handles on the cell surface, known as integrins. Cell adhesion is crucial for cell survival and proliferation. Growth factors are also found in the ECM for cell organization. Some growth factors promote blood vessel formation, which can provide nutrients for cells. Therefore, a simple artificial environment should include various biological signals found in the ECM.

Currently, there are natural and synthetic scaffolds that are being used to generate the optimal environment for cells. Natural polymers such as collagen, chitosan or glycosaminoglycans, and synthetic polymers, including polylactic acid, polyglycolic acid, polycaprolactone or self-assembled nanofibers, are some of the materials used or considered for scaffold production. Natural polymers can be obtained easily, however biological contamination is a concern since they are produced using components from animals or microorganisms. Synthetic polymers can usually avoid the problem of contamination. Sometimes the ability to process the polymers can be problematic. Researchers have developed self-assembled nanofibers to overcome the problems that arise with synthetic and natural polymers. These nanofibers are composed of small molecules which are programmed to come together under control and to form larger structures. The nanofibers in the solution can form a three-dimensional network and convert into a self-supporting gel which can encapsulate cells as an artificial scaffold. In general, small bioactive molecules can be conjugated to the self-assembled molecules or can be encapsulated in situ in the 3-D network of fibers.

One of the recent uses of tissue engineering is to replace tissue that has been damaged by cancer. Cancer surgery is one of the most challenging types of surgery in that the defective tissue must be reconstructed afterwards. Improvement in surgical technology gives the chance of transferring a tissue from different sites of the body but unfortunately most of the time it is not the same tissue, and does not have the same texture or function. Reconstructing a resected tongue or the feeding tube is possible with the use of skin from the leg or forearm. But this skin does not provide the normal mucosal function, so it does not enable taste or sense to be perceived in the same way nor does it produce mucus in the same way. Together with advances in tissue engineering surgeons have started using the tissue-engineered mucosa of patients to reconstruct the mouth and feeding passage defects, instead of using the skin from chest, leg or forearm skin. These clinical applications of tissue engineering are in their very early stages, but it would not be surprising if we were able to reconstruct a lost organ from a similar one in the future. It would be exciting to be able to replace the tongue of a tongue cancer patient with a brand new tongue grown from his/her own tissues produced in a laboratory. Tasting the same…sensing the same…moving and even articulating the same…instead of having a piece of meat from another part of the body…

Innovative and imaginative work which has been inspired by natural materials demonstrates how the treatment of organ malfunctions is feasible. Efforts in biotechnology to develop tissue-engineered products will benefit many people who are searching for a healthier life. Potentially, in the near future, tissue-engineered products will be more widely used to treat bone fractures, serious skin burns, spinal cord injuries, diabetes, and heart diseases. Before implanting the tissue-engineered products, it is vital that there be extensive testing of the materials to be used. Toxicology and efficacy studies should be performed on the materials to prevent damage to the original healthy cells, and the new cells and regenerated tissue must be compared to original healthy cells and tissue.

Mustafa Guler has a PhD in chemistry. He is currently a research associate at Northwestern University, Chicago, IL. Joseph Coreman is a medical doctor at the Ohio State University Medical College, Columbus, OH.

References

• Khariwala SS, Vivek PP, Lorenz RR, Esclamado RM, Wood B, Strome M, Alam DS. Swallowing outcomes after microvascular head and neck reconstruction: a prospective review of 191 cases. Laryngoscope. 2007 Aug; 117(8):1359-63.
• Sauerbier S, Gutwald R, Wiedmann-Al-Ahmad M, Lauer G, Schmelzeisen R. Clinical application of tissue-engineered transplants. Part I: mucosa. Clin Oral Implants Res. 2006 Dec; 17(6):625-32.
• Hotta T, Yokoo S, Terashi H, Komori T. Clinical and histopathological analysis of healing process of intraoral reconstruction with ex vivo produced oral mucosa equivalent. Kobe J Med Sci. 2007;53(1-2):1-14.
• Ratner, Buddy D. “Biomaterials Science – An Introduction to Materials in Medicine” Elsevier, 2004.
• Lanza, Robert P., Robert S. Langer, William L. Chick, “Principles of Tissue Engineering”, Academic Press, 1997.
• Alberts, Bruce, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter, “Molecular Biology of the Cell” Garland Science, 2002.