Penn researchers help break ground on method to transform cells
Doctors have found a way to manipulate wounds to heal as regenerated skin rather than scar tissue. The method involves transforming the most common type of cells found in wounds into fat cells – something that was previously thought to be impossible in humans. Researchers began this work at the Perelman School of Medicine at the University of Pennsylvania, which led to a large-scale, multi-year study in connection with the Plikus Laboratory for Developmental and Regenerative Biology at the University of California, Irvine. They published their findings online in the journal Science on Thursday, January 5th, 2017.
Fat cells called adipocytes are normally found in the skin, but they’re lost when wounds heal as scars. The most common cells found in healing wounds are myofibroblasts, which were thought to only form a scar. Scar tissue also does not have any hair follicles associated with it, which is another factor that gives it an abnormal appearance from the rest of the skin. Researchers used these characteristics as the basis for their work – changing the already present myofibroblasts into fat cells that do not cause scarring.
“Essentially, we can manipulate wound healing so that it leads to skin regeneration rather than scarring,” said George Cotsarelis, MD, the chair of the Department of Dermatology and the Milton Bixler Hartzell Professor of Dermatology at Penn, and the principal investigator of the project. “The secret is to regenerate hair follicles first. After that, the fat will regenerate in response to the signals from those follicles.”
The study showed hair and fat develop separately but not independently. Hair follicles form first, and the Cotsarelis lab previously discovered factors necessary for their formation. Now they’ve discovered additional factors actually produced by the regenerating hair follicle to convert the surrounding myofibroblasts to regenerate as fat instead of forming a scar. That fat will not form without the new hairs, but once it does, the new cells are indistinguishable from the pre-existing fat cells, giving the healed wound a natural look instead of leaving a scar.
As they examined the question of what was sending the signal from the hair to the fat cells, researchers identified a factor called Bone Morphogenetic Protein (BMP). It instructs the myofibroblasts to become fat. This signaling was groundbreaking on its own, as it changed what was previously known about myofibroblasts.
“Typically, myofibroblasts were thought to be incapable of becoming a different type of cell,” Cotsarelis said. “But our work shows we have the ability to influence these cells, and that they can be efficiently and stably converted into adipocytes.” This was shown in both the mouse and in human keloid cells grown in culture.
“The findings show we have a window of opportunity after wounding to influence the tissue to regenerate rather than scar,” said the study’s lead author Maksim Plikus, PhD, an assistant professor of Developmental and Cell Biology at the University of California, Irvine. Plikus began this research as a postdoctoral fellow in the Cotsarelis Laboratory at Penn, and the two institutions have continued to collaborate.
These discoveries have the potential to be revolutionary in the field of dermatology. The first and most obvious use would be to develop a therapy that signals myofibroblasts to convert into adipocytes – helping wounds heal without scarring.
“It’s highly desirable from a clinical standpoint, but right now it’s an unmet need,” Cotsarelis said.
But the increase of fat cells in tissue can also be helpful for more than just wounds. Adipocyte loss is a common complication of other conditions, especially treatments for HIV, and right now there is no efficient strategy for treatment. The cells are also lost naturally because of the aging process, especially in the face, which leads to permanent, deep wrinkles, something anti-aging treatments can’t fix in a cosmetically satisfactory way.
“Our findings can potentially move us toward a new strategy to regenerate adipocytes in wrinkled skin, which could lead us to brand new anti-aging treatments,” Cotsarelis said.
The Cotsarelis Lab is now focusing on the mechanisms that promote skin regeneration, especially with respect to hair follicle regeneration.
The Plikus Laboratory is focusing on other aspects of cell reprogramming in skin wounds. Researchers there are examining the role of other signaling factory beyond BMP as well as conducting further studies using human cells and human scar tissue.
Learn more: Using Fat to Help Wounds Heal Without Scars
UCI’s Orange County campus is the fifth-largest in the UC system, with over 28,000 students, 1,100 faculty members and 9,000 staff.
UC Irvine is considered a Public Ivy and offers 80 undergraduate degrees and 98 graduate and professional degrees.
he university is designated as having very high research activity in the Carnegie Classification of Institutions of Higher Education, and in 2009 had $325.49 million in research and development expenditures according to the National Science Foundation. UC Irvine became a member of the Association of American Universities in 1996, and is the youngest university to hold membership.
The university also administers the UC Irvine Medical Center, a large teaching hospital; the UC Irvine Health Sciences system in the City of Orange; the University of California, Irvine, Arboretum; and a portion of the University of California Natural Reserve System.
University of California, Irvine research articles from Innovation Toronto
- Battery electrode cycled 200,000 times over three months without detecting any loss of capacity or power – April 21, 2016
- Bad vibrations: UCI researchers find security breach in 3-D printing process – March 6, 2016
- One-step test for hepatitis C virus infection developed by UC Irvine Health researchers – November 15, 2015
- Man walks again after years of paralysis – September 24, 2015
- UCI neurobiologists restore youthful vigor to adult brains – May 21, 2015
- Squid-Inspired ‘Invisibility Stickers’ Could Help Soldiers Evade Detection in the Dark – March 28, 2015
- Chemists find a way to unboil eggs: Ability to quickly restore molecular proteins could slash biotechnology costs – January 31, 2015
- Satellites reveal possible catastrophic flooding months in advance, UCI finds – July 20, 2014
- Mice With MS-Like Condition Walk Again After Human Stem Cell Treatment – May 15, 2014
- Scientists Warn of Rising Oceans From Polar Melt – May 13, 2014
- Chinese herbal compound relieves inflammatory and neuropathic pain | DHCB
- UCI-led study creates new memories by directly changing the brain
- UCI researchers fabricate new camouflage coating from squid protein
- Made-to-Order Materials
- Stanford University Study Finds That Marijuana Could Help With Autism
- Satellites Show Shrinking Aquifers in Drought-Stricken Areas
- ‘Self-cleaning’ pollution-control technology could do more harm than good
- Ultra-light Aerogel Produced at a Zhejiang University Lab
- Could FastStitch Device, Invented by Undergrads, Be the Future of Suture?
- How to Overcome the “Yuck Factor” to Extend Water Supplies
- UCI researchers create mosquitoes incapable of transmitting malaria
- LED device could aid in cancer treatment
- Satellites weigh California water
- P2P Traffic Control: Wireless Technology Could Reduce Congestion, Accidents
Carbon dioxide conversion process may be adapted for biofuel synthesis
Using a novel approach involving a key enzyme that helps regulate global nitrogen, University of California, Irvine molecular biologists have discovered an effective way to convert carbon dioxide (CO2) to carbon monoxide (CO) that can be adapted for commercial applications like biofuel synthesis.
Led by Yilin Hu, UCI assistant professor of molecular biology & biochemistry at the Ayala School of Biological Sciences, the researchers found that they could successfully express the reductase component of the nitrogenase enzyme alone in the bacterium Azotobacter vinelandii and directly use this bacterium to convert CO2 to CO. The intracellular environment of the bacterium was shown to favor the conversion of CO2 in a way that would be more applicable to the future development of strategies for large-scale production of CO. The findings were surprising to the group, as nitrogenase was only previously believed to convert nitrogen (N2) to ammonia (NH3) within the bacterium under similar conditions. The full study can be found online in Nature Chemical Biology.
Hu and her colleagues knew that the intracellular environment of the bacterium Azotobacter vinelandii favors other reduction reactions, due in part to its well-known oxygen protection mechanisms and presence of physiological electron donors. But they were unsure if the intracellular environment would support the conversion of CO2 to CO.
They were excited to discover that the bacterium could reduce CO2 and release CO as a product, which makes it an attractive whole-cell system that could be explored further for new ways of recycling atmospheric CO2 into biofuels and other commercial chemical products. These findings of Hu’s group establish the nitrogenase enzyme as a fascinating template for developing approaches to energy-efficient and environmentally-friendly fuel production.
“Our observation that a bacterium can convert CO2 to CO opens up new avenues for biotechnological adaptation of this reaction into a process that effectively recycles the greenhouse gas into the starting material for biofuel synthesis that will help us simultaneously combat two major challenges we face nowadays: global warming and energy shortages,” Hu said.
Light particle could be key to understanding dark matter in universe
Recent findings indicating the possible discovery of a previously unknown subatomic particle may be evidence of a fifth fundamental force of nature, according to a paper published in the journal Physical Review Letters by theoretical physicists at the University of California, Irvine.
“If true, it’s revolutionary,” said Jonathan Feng, professor of physics & astronomy. “For decades, we’ve known of four fundamental forces: gravitation, electromagnetism, and the strong and weak nuclear forces. If confirmed by further experiments, this discovery of a possible fifth force would completely change our understanding of the universe, with consequences for the unification of forces and dark matter.”
The UCI researchers came upon a mid-2015 study by experimental nuclear physicists at the Hungarian Academy of Sciences who were searching for “dark photons,” particles that would signify unseen dark matter, which physicists say makes up about 85 percent of the universe’s mass. The Hungarians’ work uncovered a radioactive decay anomaly that points to the existence of a light particle just 30 times heavier than an electron.
“The experimentalists weren’t able to claim that it was a new force,” Feng said. “They simply saw an excess of events that indicated a new particle, but it was not clear to them whether it was a matter particle or a force-carrying particle.”
The UCI group studied the Hungarian researchers’ data as well as all other previous experiments in this area and showed that the evidence strongly disfavors both matter particles and dark photons. They proposed a new theory, however, that synthesizes all existing data and determined that the discovery could indicate a fifth fundamental force. Their initial analysis was published in late April on the public arXiv online server, and a follow-up paper amplifying the conclusions of the first work was released Friday on the same website.
The UCI work demonstrates that instead of being a dark photon, the particle may be a “protophobic X boson.” While the normal electric force acts on electrons and protons, this newfound boson interacts only with electrons and neutrons – and at an extremely limited range. Analysis co-author Timothy Tait, professor of physics & astronomy, said, “There’s no other boson that we’ve observed that has this same characteristic. Sometimes we also just call it the ‘X boson,’ where ‘X’ means unknown.”
Feng noted that further experiments are crucial. “The particle is not very heavy, and laboratories have had the energies required to make it since the ’50s and ’60s,” he said. “But the reason it’s been hard to find is that its interactions are very feeble. That said, because the new particle is so light, there are many experimental groups working in small labs around the world that can follow up the initial claims, now that they know where to look.”
Like many scientific breakthroughs, this one opens entirely new fields of inquiry.
One direction that intrigues Feng is the possibility that this potential fifth force might be joined to the electromagnetic and strong and weak nuclear forces as “manifestations of one grander, more fundamental force.”
Citing physicists’ understanding of the standard model, Feng speculated that there may also be a separate dark sector with its own matter and forces. “It’s possible that these two sectors talk to each other and interact with one another through somewhat veiled but fundamental interactions,” he said. “This dark sector force may manifest itself as this protophobic force we’re seeing as a result of the Hungarian experiment. In a broader sense, it fits in with our original research to understand the nature of dark matter.”
Approach tackles most commonly used synthetic plastic
A new way of recycling millions of tons of plastic garbage into liquid fuel has been devised by researchers from the University of California, Irvine and the Shanghai Institute of Organic Chemistry (SIOC) in China.
“Synthetic plastics are a fundamental part of modern life, but our use of them in large volume has created serious environmental problems,” said UCI chemist Zhibin Guan. “Our goal through this research was to address the issue of plastic pollution as well as achieving a beneficial outcome of creating a new source of liquid fuel.”
Guan and Zheng Huang, his collaborator at SIOC, together with their colleagues have figured out how to break down the strong bonds of polyethylene, the most common commercially available form of plastic. Their innovative technique centers on the use of alkanes, specific types of hydrocarbon molecules, to scramble and separate polymer molecules into other useful compounds. The team’s findings were published recently in Science Advances.
A study appearing April 14 in the journal Neuron suggests there may be a new way to change the damaging course of Huntington disease.
University of California, Irvine neurobiologists Leslie Thompson and Joseph Ochaba and their colleagues from UCI and from Children’s Hospital of Philadelphia have shown that reducing the aberrant accumulation of a particular form of the mutant Huntington protein corresponds to improvement in symptoms and neuroinflammation in HD mice.
They targeted and modulated levels of PIAS1 – a protein implicated in cancer and other diseases – which they found led to the reduction of the mutant Huntington protein. The work suggests that changing levels of the PIAS1 protein and targeting this pathway could have a benefit to disease. There are no current treatments for HD, although Thompson’s ongoing work with stem cell-based therapies are showing promise.