Institute for Engineering in Medicine

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Institute for Engineering in Medicine

San Diego, CA, United States
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News Article | April 17, 2017
Site: www.eurekalert.org

A team of biomedical engineering researchers, led by the University of Minnesota, has created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. The discovery is a major step forward in treating patients with tissue damage after a heart attack. The research study is published today in Circulation Research, a journal published by the American Heart Association. Researchers have filed a patent on the discovery. According to the American Heart Association, heart disease is the No. 1 cause of death in the U.S. killing more than 360,000 people a year. During a heart attack, a person loses blood flow to the heart muscle and that causes cells to die. Our bodies can't replace those heart muscle cells so the body forms scar tissue in that area of the heart, which puts the person at risk for compromised heart function and future heart failure. In this study, researchers from the University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab. When the cell patch was placed on a mouse following a simulated heart attack, the researchers saw significant increase in functional capacity after just four weeks. Since the patch was made from cells and structural proteins native to the heart, it became part of the heart and absorbed into the body, requiring no further surgeries. "This is a significant step forward in treating the No. 1 cause of death in the U.S.," said Brenda Ogle, an associate professor of biomedical engineering at the University of Minnesota. "We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years." Ogle said that this research is different from previous research in that the patch is modeled after a digital, three-dimensional scan of the structural proteins of native heart tissue. The digital model is made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells. Only with 3D printing of this type can we achieve one micron resolution needed to mimic structures of native heart tissue. "We were quite surprised by how well it worked given the complexity of the heart," Ogle said. "We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch." Ogle said they are already beginning the next step to develop a larger patch that they would test on a pig heart, which is similar in size to a human heart. The research was funded by the National Science Foundation, National Institutes of Health, University of Minnesota Lillehei Heart Institute, and University of Minnesota Institute for Engineering in Medicine. In addition to Ogle, other biomedical engineering researchers who were part of the team include Molly E. Kupfer, Jangwook P. Jung, Libang Yang, Patrick Zhang, and Brian T. Freeman from the University of Minnesota; Paul J. Campagnola, Yong Da Sie, Quyen Tran, and Visar Ajeti from the University of Wisconsin-Madison; and Jianyi Zhang, Ling Gao, and Vladimir G. Fast from the University of Alabama, To read the full research paper entitled "Myocardial Tissue Engineering With Cells Derived from Human Induced-Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold," visit the Circulation Research website.


News Article | May 9, 2017
Site: co.newswire.com

An article published in Experimental Biology and Medicine (Volume 242, Issue 9, May, 2017) describes a new treatment for minimizing injury to the heart during cardiac procedures. The study, led by Dr. Paul Iaizzo from the Department of Surgery and Institute for Engineering in Medicine at the University of Minnesota in Minneapolis, reports that administration of Deltorphin D, a delta-opioid agonist, during reperfusion improves heart function in a porcine ex vivo model system. Patients undergoing cardiac procedures such as coronary artery stenting, bypass surgery, and cardiac transplantation often experience decreased blood flow and lack of oxygen, a process called ischemia, which damages the heart. Paradoxically, additional injury to the heart can occur upon reperfusion and restoration of blood flow. One option for reducing reperfusion injury is post-conditioning, which involves treatment with adjuvant therapies at the onset of reperfusion. Although numerous agents have shown promise in preclinical trials, results from clinical trials for reperfusion injury have been disappointing. Thus, improving clinical outcomes for cardiac patients requires new insights regarding the pathophysiology and pharmacology of reperfusion injury. Several studies suggest that opioids are cardioprotective in humans and animal models when administered prior to ischemia (pre-conditioning) and at the onset of reperfusion (post-conditioning). In this study, Dr. Iaizzo and colleagues investigated the ability of Deltorphin D, a delta specific opioid agonist, to reduce reperfusion injury when administered as a supplement to the reperfusion buffer in an ex vivo reanimated swine heart; that underwent an ischemic downtime. Post-ischemic hemodynamic performance, arrhythmia burden, relative tissue perfusion, and development of necrosis were improved over the 2-hour reperfusion period, suggesting improved microvascular function. Dr. Daniel Sigg, a co-author on the study, said, “Delta opioid receptors, alone or in conjunction with other drug targets, represent a promising strategy to minimize reperfusion related cardiac injury.“ Dr. Iaizzo added that “the opportunity to utilize post-conditioning pharmacological agents to improve cardiac function will have significant applications in both cardiac surgery and transplantation.” Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said, “Iaizzo and colleagues have demonstrated that delta specific opioid agonists, such as Deltorphin D, may play an important therapeutic role in decreasing reperfusion injury during cardiac procedures.” Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit www.sebm.org. If you are interested in publishing in the journal, please visit http://ebm.sagepub.com/. Disclaimer: Newswire is not responsible for the accuracy of news releases posted to Newswire by contributing institutions or for the use of any information through the Newswire platform.


Li G.,University of Sichuan | Xu F.,Sun Yat Sen University | Zhu J.,Institute for Engineering in Medicine | Krawczyk M.,Institute for Engineering in Medicine | And 28 more authors.
Journal of Biological Chemistry | Year: 2015

PAX6 is a master regulatory gene involved in neuronal cell fate specification. It also plays a critical role in early eye field and subsequent limbal stem cell (LSC) determination during eye development. Defects in Pax6 cause aniridia and LSC deficiency in humans and the Sey (Small eye) phenotype in mice (Massé, K., Bhamra, S., Eason, R., Dale, N., and Jones, E. A. (2007) Nature 449, 1058-1062). However, how PAX6 specifies LSC and corneal fates during eye development is not well understood. Here, we show that PAX6 is expressed in the primitive eye cup and later in corneal tissue progenitors in early embryonic development. In contrast, p63 expression commences after that of PAX6 in ocular adnexal and skin tissue progenitors and later in LSCs. Using an in vitro feeder-free culture system, we show that PAX6 knockdown in LSCs led to up-regulation of skin epidermis-specific keratins concomitant with differentiation to a skin fate. Using gene expression analysis, we identified the involvement of Notch, Wnt, and TGF-β signaling pathways in LSC fate determination. Thus, loss of PAX6 converts LSCs to epidermal stem cells, as demonstrated by a switch in the keratin gene expression profile and by the appearance of congenital dermoid tissue. © 2015, American Society for Biochemistry and Molecular Biology Inc. All rights reserved.


PubMed | Sun Yat Sen University, Institute for Engineering in Medicine, University of Sichuan, Harvard University and 2 more.
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2015

PAX6 is a master regulatory gene involved in neuronal cell fate specification. It also plays a critical role in early eye field and subsequent limbal stem cell (LSC) determination during eye development. Defects in Pax6 cause aniridia and LSC deficiency in humans and the Sey (Small eye) phenotype in mice (Mass, K., Bhamra, S., Eason, R., Dale, N., and Jones, E. A. (2007) Nature 449, 1058-1062). However, how PAX6 specifies LSC and corneal fates during eye development is not well understood. Here, we show that PAX6 is expressed in the primitive eye cup and later in corneal tissue progenitors in early embryonic development. In contrast, p63 expression commences after that of PAX6 in ocular adnexal and skin tissue progenitors and later in LSCs. Using an in vitro feeder-free culture system, we show that PAX6 knockdown in LSCs led to up-regulation of skin epidermis-specific keratins concomitant with differentiation to a skin fate. Using gene expression analysis, we identified the involvement of Notch, Wnt, and TGF- signaling pathways in LSC fate determination. Thus, loss of PAX6 converts LSCs to epidermal stem cells, as demonstrated by a switch in the keratin gene expression profile and by the appearance of congenital dermoid tissue.


Microscopy image depicting fat cells (or adipocytes) after differentiation. The cells are stained with Oil Red O, which highlights lipid or fat droplets that accumulate with the fat cells. The metabolic studies described here indicated that fat cells produce these fatty acids, in part, from essential amino acids rather than sugar only. Credit: Metabolic Systems Biology lab, UC San Diego Jacobs School of Engineering Researchers at the University of California, San Diego report new insights into what nutrients fat cells metabolize to make fatty acids. The findings pave the way for understanding potential irregularities in fat cell metabolism that occur in patients with diabetes and obesity and could lead to new treatments for these conditions. The researchers published their findings online in the Nov. 16 issue of Nature Chemical Biology. "This study highlights how specific tissues in our bodies use particular nutrients. By understanding fat cell metabolism at the molecular level, we are laying the groundwork for further research to identify better drug targets for treating diabetes and obesity," said Christian Metallo, a bioengineering professor in the Jacobs School of Engineering at UC San Diego and senior author of the study. Metallo is affiliated with the Institute for Engineering in Medicine, the Moore's Cancer Center, and the CHO Systems Biology Center, all at UC San Diego. In the new study, researchers discovered that as fat cells develop, they change what types of nutrients they metabolize to produce fat and energy. Pre-adipocytes, which are precursors to fat cells, preferentially consume glucose, a simple sugar, to grow and make energy. But when pre-adipocytes become fat cells, researchers found that they metabolize not just glucose, but also branched-chain amino acids, a small set of the essential amino acids for humans. This finding is important because it shows that fat cells play an important role in regulating the body's levels of branched-chain amino acids—which are typically elevated in individuals with diabetes and obesity. "We've taken a step towards understanding why these amino acids are accumulating in the blood of diabetics and those suffering from obesity," said Courtney Green, a bioengineering Ph.D. student at UC San Diego and first author of the study. "The next step is to understand how and why this metabolic pathway becomes impaired in the fat cells of these individuals." Metallo and his team studied the metabolism of fat cells from the pre-adipocyte stage throughout the fat cell differentiation process. They induced pre-adipocytes to differentiate into fat cells and cultured the cells in media containing nutrients enriched with carbon-13 isotopes, a form of carbon atoms that are used as metabolic tracers in cells, animals, and people. Through this method, researchers were able to trace what carbon-based nutrients the cells metabolized and what they produced at different stages of the cell differentiation process. "We are curious about how different cells in our body, such as fat cells, consume and metabolize their surrounding nutrients. A better understanding of how these biochemical pathways are used by cells could help us find new approaches to treat diseases such as cancer or diabetes," said Metallo. More information: Courtney R Green et al. Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis, Nature Chemical Biology (2015). DOI: 10.1038/nchembio.1961


News Article | December 14, 2016
Site: www.rdmag.com

For the first time ever researchers at the University of Minnesota developed a robotic arm that can be controlled through the mind. Bin He, a University of Minnesota biomedical engineering professor and lead researcher on the study, explained this is a breakthrough that could help millions of people who are paralyzed or have neurodegenerative diseases. “This is the first time in the world that people can operate a robotic arm to reach and grasp objects in a complex 3D environment using only their thoughts without a brain implant,” he said in a statement. “Just by imagining moving their arms, they were able to move the robotic arm.” The arm is controlled using a noninvasive technique called electroencephalography (EEG), which is based on brain-computer interfaces. It records weak electrical activity of the subjects’ brain through a specialized, high-tech EEG cap fitted with 64 electrodes and converts the “thoughts” into action by advanced signal processing and machine learning. The researchers tested the invention on eight healthy human subjects. The participants gradually learned to imagine moving their own arm without actually moving them to control a robotic appendage in 3D space. The subjects improved from initially being able to control a virtual cursor on a computer screen to being able to control a robotic arm to reach and grasp objects in fixed locations on a table to a three-layer shelf by only thinking about the movements. Average success rates for the eight subjects in controlling the robotic arm and picking up objects in fixed locations was above 80 percent and the success rate in moving objects from the table onto the shelf was above 70 percent. “This is exciting as all subjects accomplished the tasks using a completely non-invasive technique,” He said. “We see a big potential for this research to help people who are paralyzed or have neurodegenerative diseases to become more independent without a need for surgical implants.” The brain-computer interface is able to work due to the geography of the motor cortex—the area of the cerebrum that governs movement. Neurons in the motor cortex produce tiny electric currents when humans move or think about a movement. When a human thinks about a different movement it activates a new assortment of neurons, a phenomenon confirmed by cross-validation using functional MRI in He’s previous study. According to He, sorting out these assortments using advanced signal processing laid the groundwork for the brain-computer interface used by University of Minnesota. The robotic arm is seen as an advancement of his previous research. “Three years ago, we weren’t sure moving a more complex robotic arm to grasp and move objects using this brain-computer interface technology could even be achieved,” He said. “We’re happily surprised that it worked with a high success rate and in a group of people.” He said the next step would be to further develop the brain-computer interface technology realizing a brain-controlled robotic prosthetic limb attached to a person’s body or examine how the technology could work with someone who has had a stroke or is paralyzed. In addition to He, who also serves as director of the University of Minnesota Institute for Engineering in Medicine, the research team includes biomedical engineering postdoctoral researcher Jianjun Meng (first author); biomedical engineering graduate student Bryan Baxter; Institute for Engineering in Medicine staff member Angeliki Bekyo; and biomedical engineering undergraduate students Shuying Zhang and Jaron Olsoe. The researchers are affiliated with the University of Minnesota College of Science and Engineering and the Medical School. The study was published in Scientific Reports.


Researchers at the University of Minnesota have made a major breakthrough that allows people to control a robotic arm using only their minds. The research has the potential to help millions of people who are paralyzed or have neurodegenerative diseases. The study is published online today in Scientific Reports, a Nature research journal. "This is the first time in the world that people can operate a robotic arm to reach and grasp objects in a complex 3D environment using only their thoughts without a brain implant," said Bin He, a University of Minnesota biomedical engineering professor and lead researcher on the study. "Just by imagining moving their arms, they were able to move the robotic arm." The noninvasive technique, called electroencephalography (EEG) based brain-computer interface, records weak electrical activity of the subjects' brain through a specialized, high-tech EEG cap fitted with 64 electrodes and converts the "thoughts" into action by advanced signal processing and machine learning. Eight healthy human subjects completed the experimental sessions of the study wearing the EEG cap. Subjects gradually learned to imagine moving their own arms without actually moving them to control a robotic arm in 3D space. They started from learning to control a virtual cursor on computer screen and then learned to control a robotic arm to reach and grasp objects in fixed locations on a table. Eventually, they were able to move the robotic arm to reach and grasp objects in random locations on a table and move objects from the table to a three-layer shelf by only thinking about these movements. All eight subjects could control a robotic arm to pick up objects in fixed locations with an average success rate above 80 percent and move objects from the table onto the shelf with an average success rate above 70 percent. "This is exciting as all subjects accomplished the tasks using a completely noninvasive technique. We see a big potential for this research to help people who are paralyzed or have neurodegenerative diseases to become more independent without a need for surgical implants," He said. The researchers said the brain-computer interface technology works due to the geography of the motor cortex--the area of the cerebrum that governs movement. When humans move, or think about a movement, neurons in the motor cortex produce tiny electric currents. Thinking about a different movement activates a new assortment of neurons, a phenomenon confirmed by cross-validation using functional MRI in He's previous study. Sorting out these assortments using advanced signal processing laid the groundwork for the brain-computer interface used by the University of Minnesota researchers, He said. The robotic arm research builds upon He's research published three years ago in which subjects were able to fly a small quadcopter using the noninvasive EEG technology. The research gained international media attention. "Three years ago, we weren't sure moving a more complex robotic arm to grasp and move objects using this brain-computer interface technology could even be achieved," He said. "We're happily surprised that it worked with a high success rate and in a group of people." He anticipates the next step of his research will be to further develop this brain-computer interface technology realizing a brain-controlled robotic prosthetic limb attached to a person's body or examine how this technology could work with someone who has had a stroke or is paralyzed. In addition to Professor He, who also serves as director of the University of Minnesota Institute for Engineering in Medicine, the research team includes biomedical engineering postdoctoral researcher Jianjun Meng (first author); biomedical engineering graduate student Bryan Baxter; Institute for Engineering in Medicine staff member Angeliki Bekyo; and biomedical engineering undergraduate students Shuying Zhang and Jaron Olsoe. The researchers are affiliated with the University of Minnesota College of Science and Engineering and the Medical School. The University of Minnesota study was funded by the National Science Foundation (NSF), the National Center for Complementary and Integrative Health, National Institute of Biomedical Imaging and Bioengineering, and National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH), and the University of Minnesota's MnDRIVE (Minnesota's Discovery, Research and InnoVation Economy) Initiative funded by the Minnesota Legislature. To read the full research paper, entitled "Noninvasive Electroencephalogram Based Control of a Robotic Arm for Reach and Grasp Tasks," visit the Nature Scientific Reports website.

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