Heart-muscle patches made with human cells improve heart attack recoveryJanuary 10, 2018
BIRMINGHAM, Ala. - Large, human cardiac-muscle patches created in the lab have been tested, for the first time, on large animals in a heart attack model. This clinically relevant approach showed that the patches significantly improved recovery from heart attack injury.
The results are a step closer to the goal of treating human heart attacks by suturing cardiac-muscle patches over an area of dead heart muscle in order to reduce the pathology that often leads to heart failure.
The research was led by Jianyi "Jay" Zhang, M.D., Ph.D., the chair of University of Alabama at Birmingham Biomedical Engineering, a joint department of the UAB School of Medicine and the UAB School of Engineering.
Each patch is 1.57 by 0.79 inches in size and nearly as thick as a dime. Zhang and colleagues found that transplanting two of these patches onto the infarcted area of a pig heart significantly improved function of the heart's left ventricle, the major pumping chamber. The patches also significantly reduced infarct size, which is the area of dead muscle; heart-muscle wall stress and heart-muscle enlargement; as well as significantly reducing apoptosis, or programmed cell death, in the scar boarder area around the dead heart muscle. Furthermore, the patches did not induce arrhythmia in the hearts, a serious complication observed in some past biomedical engineering approaches to treat heart attacks.
A key to success of the patches is how they are engineered.
Each patch is a mixture of three cell types -- 4 million cardiomyocytes, or heart-muscle cells; 2 million endothelial cells, which are well-known to help cardiomyocytes survive and function in a micro-environment; and 2 million smooth muscle cells, which line blood vessels. The three cell types were differentiated from cardiac-lineage, human induced pluripotent stem cells, or hiPSCs, rather than using hiPSCs created from skin cells or other cell types.
Each patch was grown in a three-dimensional fibrin matrix that was rocked back and forth for a week. The cells begin to beat synchronously after one day.
This mixture of three cell types and the dynamic rocking produced more heart muscle cells that were more mature, with superior heart-muscle physiological function and contractive force, as compared with patches made from a monolayer of cells that are not dynamically rocked. The patches resembled native heart-muscle tissue in their physiological and contractile properties.
Past attempts to use hiPSCs to treat animal models of heart attacks -- using an injection of cells or cells grown as a very thin film -- have shown very low rates of survival, or engraftment, by the hiPSCs. The present study had a relatively high rate of engraftment, 10.9 percent, four weeks after transplantation, and the transplantation led to improved heart recovery.
Part of the beneficial effects of the patches may occur through the release of tiny blebs called exosomes from cells in the patches. These exosomes, which carry proteins and RNA from one cell to another, are a common cell-to-cell signaling method that is incompletely understood. In tissue culture experiments, the researchers found that exosomes released from the large heart-muscle patches appeared to protect the survival of heart-muscle cells.
Additionally, the patches appeared to prevent or reverse detrimental changes in protein phosphorylation in the sarcomeres of the heart-muscle tissue bordering the infarcted area of the heart. This result is the first to suggest that hiPSC-derived heart cells may improve contractile function after heart attacks by lessening maladaptive changes in phosphorylation states of sarcomeric proteins. The sarcomere is the contractile unit in a heart-muscle cell myofibril.
This work was supported by National Institutes of Health grants HL 99507, HL114120, HL131017, HL134764, HL128086 and HL109810; and by Shared Instrumentation Grant Program OD018475.
At UAB, Zhang holds the T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership.
University of Alabama at Birmingham
Related Engineering Articles:
E. coli may have potentially harmful effects but scientists in Australia have discovered this bacterium produces a toxin which binds to an unusual sugar that is part of carbohydrate structures present on cells not usually produced by healthy cells.
The Wyss Institute for Biologically Inspired Engineering and the University of Zurich announced today a cross-institutional team effort to generate a functional heart valve replacement with the capacity for repair, regeneration, and growth.
The Mackenzie Dike Swarm and the roughly 120 other known giant dike swarms located across the planet may also provide useful information about efficient extraction of oil and natural gas in today's modern world.
Academically strong, low-income would-be engineers get the boost they need to complete their undergraduate degrees.
Professor Ron Hui, Chair Professor of Power Electronics and Philip Wong Wilson Wong Professor of Electrical Engineering at the University of Hong Kong, has been named a Fellow by the Royal Academy of Engineering, UK, one of the most prestigious national academies.
The often-maligned E. coli bacteria has powerhouse potential: in the lab, it has the ability to crank out fuels, pharmaceuticals and other useful products at a rapid rate.
Raresh Pascali, instructional associate professor in the Mechanical Engineering Technology Program at the University of Houston, has been named the 2016 recipient of the Ross Kastor Educator Award.
A team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A.
University of Utah engineers have discovered a new kind of 2-D semiconducting material for electronics that opens the door for much speedier computers and smartphones that also consume a lot less power.
A University of Bristol academic has been elected a Fellow of the world's largest and most prestigious professional association for the advancement of technology.
Related Engineering Reading:
Basic Machines and How They Work
by Naval Education And Training Program (Author)
This revised edition of an extremely clear Navy training manual leaves nothing to be desired in its presentation. Thorough in its coverage of basic theory, from the lever and inclined plane to internal combustion engines and power trains, it requires nothing more than an understanding of the most elementary mathematics.
Beginning with the simplest of machines — the lever — the text proceeds to discussions of the block and tackle (pulleys and hoists), wheel and axle, the inclined plane and the wedge, the screw, and different types of gears (simple, spur, bevel, herringbone, spiral,... View Details
The Book of Massively Epic Engineering Disasters: 33 Thrilling Experiments Based on History's Greatest Blunders (Irresponsible Science)
by Sean Connolly (Author)
It’s hands-on science with a capital “E”—for engineering.
Beginning with the toppling of the Colossus of Rhodes, one of the seven wonders of the ancient world, to the destructive, laserlike sunbeams bouncing off London’s infamous “Fryscraper” in 2013, here is an illustrated tour of the greatest engineering disasters in history, from the bestselling author of The Book of Totally Irresponsible Science.
Each engineering disaster includes a simple, exciting experiment or two using everyday household items to explain the underlying science and put... View Details
Mechanical Engineering Reference Manual for the PE Exam, 13th Ed
by Michael R. Lindeburg PE (Author)
Get your PE Mechanical Study Schedule and PE Mechanical Reference Manual index at ppi2pass.com/downloads.
** New Practice Exams and Six-Minute Problem Books Now Available for New PE Mechanical Exams**
The following new titles are available from the Publisher PPI on Amazon. Free study schedules to support the new exams are available on ppi2pass.com.
PE Mechanical HVAC and Refrigeration Practice Exam (MEHRPE), PE Mechanical Thermal and Fluids Systems Practice Exam (METSPE), and PE Mechanical Machine Design and Materials Practice Exam... View Details
Civil Engineering Reference Manual for the PE Exam, 15th Ed
by Michael R. Lindeburg PE (Author)
16TH EDITION AVAILABLE SOON
Upgrade your review with PPI’s Civil PE prep course and a passing guarantee. This prep course provides expert instruction, a structured syllabus, PPI's #1 selling review materials, and convenient online viewing from the comfort of home or on the go. Visit ppi2pass to learn more and enroll.
Get your CERM15 code updates and Civil Engineering Reference Manual index at ppi2pass.com/downloads.
Comprehensive Civil PE Exam Coverage
The Civil Engineering Reference Manual is the most comprehensive... View Details
Shigley's Mechanical Engineering Design (McGraw-Hill Series in Mechanical Engineering)
by Richard G Budynas (Author), Keith J Nisbett (Author)
Shigley's Mechanical Engineering Design is intended for students beginning the study of mechanical engineering design. Students will find that the text inherently directs them into familiarity with both the basics of design decisions and the standards of industrial components. It combines the straightforward focus on fundamentals that instructors have come to expect, with a modern emphasis on design and new applications. The tenth edition maintains the well-designed approach that has made this book the standard in machine design for nearly 50 years. View Details
Studying Engineering: A Road Map to a Rewarding Career (Fourth Edition)
by Raymond B. Landis (Author)
About the Book
Since Studying Engineering: A Road Map to a Rewarding Career exploded onto the market in 1995, it has become the best selling Introduction to Engineering textbook of all time. Adopted by over 300 U.S. institutions, and reaching more than 150,000 students, the book has made major inroads into the "sink or swim" paradigm of engineering education. Armed with the book as a powerful tool for "student development," large numbers of engineering programs have implemented Introduction to Engineering courses to improve the academic performance and retention rates of their... View Details
The Existential Pleasures of Engineering (Thomas Dunne Book)
by Samuel C. Florman (Author)
Humans have always sought to change their environment--building houses, monuments, temples, and roads. In the process, they have remade the fabric of the world into newly functional objects that are also works of art to be admired. In this second edition of his popular Existential Pleasures of Engineering, Samuel Florman explores how engineers think and feel about their profession.
A deeply insightful and refreshingly unique text, this book corrects the myth that engineering is cold and passionless. Indeed, Florman celebrates engineering not only crucial and fundamental but... View Details
Practical Electronics for Inventors, Fourth Edition
by Paul Scherz (Author), Simon Monk (Author)
A Fully-Updated, No-Nonsense Guide to Electronics
Advance your electronics knowledge and gain the skills necessary to develop and construct your own functioning gadgets. Written by a pair of experienced engineers and dedicated hobbyists, Practical Electronics for Inventors, Fourth Edition, lays out the essentials and provides step-by-step instructions, schematics, and illustrations. Discover how to select the right components, design and build circuits, use microcontrollers and ICs, work with the latest software tools, and test and tweak your creations. This... View Details
Unwritten Laws of Engineering: Revised and Updated Edition
by W. J. King (Author), James G. Skakoon (Author)
This fully revised and updated edition of the 1944 classic serves as a crucial compilation of 'house rules' or a professional code. This new edition keeps the style of the original and much of its content. Changes reflect shifted societal values, changed employment laws and evolved corporate structures. Packed with contemporary examples, this new volume is a must for those entering the engineering field or for those interested in improving their professional effectiveness. View Details
Inner Engineering: A Yogi's Guide to Joy
by Sadhguru (Author)
NEW YORK TIMES BESTSELLER • Thought leader, visionary, philanthropist, mystic, and yogi Sadhguru presents Western readers with a time-tested path to achieving absolute well-being: the classical science of yoga.
NAMED ONE OF THE TEN BEST BOOKS OF THE YEAR BY SPIRITUALITY & HEALTH
The practice of hatha yoga, as we commonly know it, is but one of eight branches of the body of knowledge that is yoga. In fact, yoga is a sophisticated system of self-empowerment that is capable of harnessing and activating inner energies in such a way that your body and... View Details