Source of cells used to generate new tissue may be important to personalized medicine

Significant investments are being made worldwide in precision medicine, concentrated in the curation of stem cell lines for the generation of new tissues and organs. Specialists have primarily relied on skin samples as their source of cells because of the ability of these cells to grow in culture and the relative ease of acquisition and manipulation in the laboratory. As momentum and investment continue to build towards this revolution in personalized medicine, Dr. Jaffe and his team have discovered that both the location and age of cell samples from patients have important considerations when generating patient-specific stem cell lines.

The most popular cell types for generating patient-specific stem cells are skin-derived and therefore receive potentially the highest amount of environmental exposure. LIBD investigators compared fibroblast lines from dura mater of the postmortem brain to those from skin samples in the same individuals. While the cells appear identical under a microscope, this study identified widespread epigenetic and gene expression differences, suggesting strong epigenetic memory from the cell’s original location in the body. In addition, researchers discovered sites that were significantly associated with the age of the donor. Dr. Jaffe noted, “These age-related changes are one of the first examples, to our knowledge, of significant age-related changes in a pure cell population that is many divisions from the original cells.”

The results of this study show there are significant differences in the cells derived from dura vs skin samples across the lifespan. As the field of personalized medicine continues to grow, this evidence necessitates further exploration into the epigenetic patterns in stem cells used for new tissue and organ generation. Additional research is required to determine which cells to cultivate and when, as researchers question how much epigenetic memory is actually erased when creating stem cell models.

Source of cells used to generate new tissue may be important to personalized medicine

Blood-flow sensor for vascular disease monitoring developed, tested

In a study published in the Oct. 30, 2015 issue of Science Advances, the researchers showed that the sensor can measure blood flow in both large and micro-sized blood vessels near the skin’s surface. They also provided details about the design and operation of the device. The researchers assessed the sensor’s performance under various conditions, showing that the technology could be used for continuous blood-flow monitoring during daily activities and in a variety of clinical research and health care settings.

In addition to diabetes and chronic hypertension, conditions that affect the health of blood vessels and surrounding tissue include kidney disease, autoimmune and other inflammatory conditions, the effects of aging and smoking, and a class of cholesterol-related abnormalities called dyslipidemias. Continuous monitoring of variations in blood flow could also be valuable in assessing these conditions in clinical and research scenarios.

The pilot-tested device, co-developed with researchers at Northwestern University, is among a variety of tools available to measure blood flow.. Other devices, such as ones based on optical or acoustic methods, however, do not work as well when the body is in motion, and thus require a patient or study subject to remain still.

The researchers overcame these challenges with the soft, skin-conforming electronic device that is applied directly onto the skin and uses thermal sensors to collect data on changes in temperature, including those caused by changes in blood flow. The device can also apply a small amount of heat in order to test a subject’s responses. In this mode, a miniature pad in the device generates a heat impulse, while 14 surrounding thermal sensors detect the resulting heat flux. The signal is sent to a computer that calculates the velocity of blood flow occurring within two millimeters of the skin surface.

In their study, the researchers placed the sensor on a study subject’s forearm, over a large, visible vein, and then applied pressure for 60 seconds at various positions near the vein. Each time, the device sensed corresponding reductions in blood flow. The researchers also used a thermal camera that measures infrared signals to confirm that the blood-flow sensor measurements were accurate, even when the subject moved around.

Next, they chose a placement on the forearm that was not near a large vein, so that the device would detect blood flow in micro-sized blood vessels within the underlying tissue. The researchers were able to detect changes in blood flow when the study subject took a deep breath. Members of the team at a collaborating institution performed a separate test that involved delivering a gentle slap to the skin near the electronic sensor, which caused a mild reddening reaction. The sensor registered the skin reaction as an increase of surface temperature, accompanied by a change in the direction of blood flow within two millimeters of the skin’s surface.

According to co-author Alexander Gorbach, Ph.D., head of NIBIB’s Infrared Imaging and Thermometry Unit, the tests performed with the thermal sensor helped to establish a number of guidelines for its use, such as optimal placement of the sensor, and how deeply under the skin’s surface the device can assess blood flow. At this stage, the device shows promise as a low-cost, readily-fabricated sensor for use in ambulatory or hospital-based settings. Because of the link between chronic hypertension and some types of vascular diseases, the new sensor may be a useful addition to studies of hypertension and its consequences.

Dr. Gorbach had taken part in prior research, published in 2013, that tested the electronic sensor’s use for collecting continuous body temperature readings. In that study, the team tested the device for use in monitoring the skin temperature of patients under observation for infection or other illnesses. “The clinical standard for temperature readings is two times per day, but this device can send readings two times per second,” he said. In addition, the device can also be used during surgery to monitor the temperature and blood flow of internal organs.

Blood-flow sensor for vascular disease monitoring developed, tested

Groundbreaking discovery made use skin cells to kill cancer

The technique, reported in Nature Communications, builds on a newest chronicle of a Nobel Prize-winning record from 2007, that authorised researchers to spin skin cells into embryonic-like branch cells. Researchers hailed a possibilities for use in regenerative medicine and drug screening. Now, researchers have found a new use: murdering mind cancer.

“Patients desperately need a improved customary of care,” pronounced Shawn Hingtgen, Ph.D., an partner highbrow in a UNC Eshelman School of Pharmacy and member of a Lineberger Comprehensive Care Center, who led a study.

The presence rate over dual years for a studious with a glioblastoma is 30 percent since it is so formidable to treat. Even if a surgeon removes many of a tumor, it’s scarcely unfit to get a invasive, carcenogenic tendrils that widespread deeper into a mind and fundamentally a ruins grow back. Most patients die within a year and a half of their diagnosis.

Hingtgen and his group wish to urge those statistics by building a new personalized diagnosis for glioblastoma that starts with a patient’s possess skin cells, with a idea of removing absolved of a carcenogenic tendrils, effectively murdering a glioblastoma.

In their work, Hingtgen and his group reprogram skin cells famous as fibroblasts — that furnish collagen and junction hankie — to turn prompted neural branch cells. Working with mice, Hingtgen’s group showed that these neural branch cells have an inherited ability to pierce via a mind and home in on and kill any remaining cancer cells. The group also showed that these branch cells could be engineered to furnish a tumor-killing protein, adding another blow to a cancer.

Depending on a form of tumor, a Hingtgen’s group increasing presence time of a mice 160 to 220 percent. Next stairs will concentration on tellurian branch cells and contrast some-more effective anti-cancer drugs that can be installed into a tumor-seeking neural branch cells.

“Our work represents a newest expansion of a stem-cell record that won a Nobel Prize in 2012,” Hingtgen said. “We wanted to find out if these prompted neural branch cells would home in on cancer cells and either they could be used to broach a healing agent. This is a initial time this approach reprogramming record has been used to provide cancer.”

Hingtgen’s group is also now improving a staying energy of branch cells within a surgical cavity. They detected that a branch cells indispensable a earthy pattern to support and classify them, so they will hang around prolonged adequate to find out a carcenogenic tendrils. “Without a structure like that, a branch cells ramble off too fast to do any good,” pronounced Hingtgen, who reported this outcome in a apart biography called Biomaterials.

In that study, Hingtgen and his group combined his branch cells to an FDA-approved fibrin sealant ordinarily used as surgical glue. The earthy pattern it creates tripled a influence of branch cells in a surgical cavity, providing serve support for a qualification and strength of a technique.

Groundbreaking discovery made use skin cells to kill cancer

Skin infections rife among high school wrestlers, say researchers

The study, published in a Feb emanate of a Journal of a American Academy of Dermatology, examined information from a vast inhabitant representation of U.S. high schools over 5 years and found that 73.6 percent of skin infections occurred during wrestling followed by football with 17.9 percent. The control and neck were a many visit site of infection.

“Given a inlet of a sport, it’s not startling that wrestlers humour a many skin infections,” pronounced comparison author Robert Dellavalle, MD, associate highbrow of dermatology during a University of Colorado School of Medicine. “Most of a infections were bacterial and fungal.”

Most athletes were means to lapse to play within 3 to 6 days though some of a infections were some-more serious.

“While many skin infections need a week liberation on average, others might have some-more critical eye and neurological impasse from a primary Herpes Simplex Virus,” pronounced investigate co-first author Kurt Ashak, a fourth year medical tyro during Michigan State University who helped control a investigate during a new dermatology revolution during CU Anschutz.

The investigate used information from a National High School Sports-Related Injury Surveillance System, High School RIO (Reporting Information Online), destined by Dawn Comstock, PhD, associate highbrow of epidemiology during a Program for Injury Prevention, Education and Research (PIPER) during a Colorado School of Public Health.

They looked during 22 high propagandize sports and found 474 skin infections reported during 20.858,781 ‘athlete exposures’ (AE) or one contestant participating in one practice, competition, or performance.

The rate of skin infections in wrestling was 28.56 per 100,000 AE while football rates were 2.32 per 100,000. Other sports had rates of skin infections reduction than 1.00 per 100,000 AE with 8 stating nothing during all.

Some 60.6 percent of skin infections were bacterial followed by tinea (ringworm) during 28.4 percent. The investigate showed herpetic lesions like cold sores and heat blisters represented 5.2 percent of infections while 3.2 percent were diverse infections.

“A series of best practices are accessible to forestall sports-related skin infections,” pronounced investigate co-first author Kyle Burton, a fourth-year medical tyro during a University of Central Florida, who also did a investigate during a dermatology investigate revolution during CU Anschutz. “For example, a Centers for Disease Control and Prevention now recommends that athletes take showers directly after any competition.”

Burton pronounced if immersion directly after any foe and use is not possible, studies have shown that skin infections also dump dramatically when athletes use soap and H2O skin wipes. A recommendation from a National Federation of State High School Athletic Associations calls for referees to perform skin checks before any wrestling compare in an try to forestall athletes from swelling infections.

Dr. Dellavalle remarkable that many schools clean down wrestling mats before and after competitions though given that many infections start on a control and face, they should be some-more observant about headgear.

“Wrestlers are not rubbing their heads and faces on a mats,” he said. “The problem might be not gripping headgear scrupulously spotless before any match.”

Skin infections rife among high school wrestlers, say researchers

Smart skin made of recyclable materials may transform medicine and robotics

The flexible, paper-based skin is layered onto a post-it note, with paper, aluminum foil, lint-free wipes, and pencil lines behaving as intuiting components. Being done of recyclable materials, this paper skin presents a vast series of feeling functions in a inexpensive and environmentally accessible way.

“Democratization of wiring will be pivotal in a destiny for a continued growth. In that regard, a skin-type feeling height done with recyclable materials usually demonstrates a energy of tellurian imagination,” pronounced Prof. Muhammad Mustafa Hussain, comparison author of a Advanced Materials Technologies paper. “This is a initial time a unaccompanied height shows multi-sensory functionalities tighten to that of healthy skin. Additionally they are being review or monitored concurrently like the possess skin.”

Smart skin made of recyclable materials may transform medicine and robotics

First topical treatment for common benign skin lesions

“Our paper is a initial to uncover that SKs are contingent on an enzyme called Akt for survival,” says Victor Neel, MD, PhD, MGH executive of Dermatologic Surgery and lead author of a paper. “Inhibition of this enzyme in SK cells causes fast dungeon genocide while carrying no outcome on normal skin cells. We are assured that this paper heralds a expansion of an effective, accepted diagnosis for SKs.”

Sometimes called “senile warts,” “barnacles” or “liver spots,” SKs change in tone from tan to black, can be prosaic or raised, and operation in distance from utterly tiny to an in. or some-more across. They turn some-more common with aging; many people over 40 are expected to have a few, and some can have hundreds sparse opposite a torso and face. While SKs have some little facilities in common with their virulent reflection squamous dungeon carcinoma and many have mutations in genes famous to be concerned in cancer, SKs never turn malignant.

Previous examine by members of a MGH group identified increasing countenance in SKs of expansion cause receptors and other genes suspicion to be concerned in skin dungeon split and in skin cancer development. Neel explains, “We still don’t know because SKs conflict virulent mutation yet we consider investigate SKs will assistance us brand factors that forestall soft lesions from apropos malignant.

The dual genes that are many frequently deteriorated in SKs — called PI3K and FGFR3 — formula for proteins that impact a activation of a Akt kinase enzyme, that is famous to retard several cell-death associated pathways. Although prior studies have reported aloft levels of activated Akt in SKs than in normal skin, last a stress of that anticipating was hampered by a inability to grow SK cells in a laboratory. Through hearing and blunder and a bit of luck, a MGH group identified conditions that assent SK cells to be cultured, opening adult an array of opportunities for investigate their biology.

Cultured SK cells were unprotected to a row of specific kinase inhibitors, confirming that a expansion and upkeep of SK cells requires a participation of activated Akt. One sold Akt inhibitor, called A44 (A-443654, constructed by Abbvie Pharmaceuticals), was by distant a many fit during inducing a genocide of well-bred SK cells. Small doses of A44 instituted a cell-death module called apoptosis. The researchers also found that requesting A44 to total SK lesions that had been excised from patients’ skin and confirmed in enlightenment caused a lesions to die by apoptosis.

“Within 48 hours of bearing to A44, a SK lesions from patients totally disintegrated,” says co-author Anna Mandinova, MD, PhD, of MGH’s Cutaneous Research Biology Center. “This outcome was really specific to SK lesions, as A44 was submissive both to normal skin cells and to virulent squamous dungeon carcinoma cells.”

The MGH group is stability to examine a intensity of A44 and several other compounds in sequence to brand a best claimant for clinical trials of a accepted diagnosis for SKs. A obvious focus formed on a investigate commentary has been filed, and a group is stability to pursue what SKs can exhibit about a molecular differences between soft and virulent tumors.

“Understanding because SKs never turn malignant, even yet they have mutations in classical oncogenes, was a primary doubt we wanted to residence when we started investigate this skin lesion. Finding a novel inhibitor of SKs was a serendipitous byproduct of that inquiry,” says Neel, who is an partner highbrow of Dermatology during Harvard Medical School. “We think that other, yet-to-be-determined mutations in SKs are exclusive with a mutations that lead to malignancy. For example, p53 is ordinarily deteriorated both in sun-damaged skin and in cancers like squamous dungeon carcinoma yet is never deteriorated in SKs. We wish that pinpointing other mutations underlying SK expansion will assistance us know how they conflict apropos malignant, that could surprise us of new ways of treating some-more dangerous tumors.”

First topical treatment for common benign skin lesions

Food additive that may prevent skin cancer revealed by scientists

Georg Wondrak, PhD, associate professor, and Donna Zhang, PhD, professor, both members of a University of Arizona Cancer Center, recently published a investigate in Free Radical Biology and Medicine titled, “System Administration of a Apocarotenoid Bixin Protects Skin opposite Solar UV-Induced Damage by Activation of Nrf2.”

Bixin is a splendid reddish orange devalue found in annatto, a healthy seasoning and food coloring subsequent from a seeds of a achiote fruit. Annatto, also famous as achiote, has been a common part in Latin American cooking given a pre-Columbian era.

Dr. Wondrak’s lab works to find tiny molecules, mostly in succulent plants, that can forestall skin cancer. Dr. Zhang is a heading consultant on a Nrf2 transcription factor, that strengthens cells opposite bearing to carcinogens. Dr. Wondrak’s investigations spasmodic brand a devalue that activates a Nrf2 pathway, and he calls on Dr. Zhang to combine in last either a devalue has cancer-preventive properties.

In a new study, mice injected with bixin and uninjected mice were unprotected to UV radiation. The mice with a bixin injection gifted most reduction serious skin object damage.

Dr. Wondrak says this find is singular since bixin is a nutritive factor, not a sunscreen practical to a skin. It prevents UV skin repairs from a inside out by inducing cells to make protecting antioxidants and correct factors. The devalue does not kill skin cancer cells, though prevents their combining in a initial place. Drs. Wondrak and Zhang find this investigate generally constrained since it involves a ordinarily consumed food substance.

The subsequent stairs for this line of investigate embody anticipating out either bixin prevents UV skin repairs in humans as it does in mice. Because annatto is authorized by a Food and Drug Administration asa protected food additive, the use in destiny clinical trials is approaching to need fewer rounds of testing. With continued investigate into bixin’s effects, scientists shortly might know if dishes with annatto can assistance forestall object damage, photo-aging and cancer in humans.

Food additive that may prevent skin cancer revealed by scientists