Nav: Home

Heart-muscle patches made with human cells improve heart attack recovery

January 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.
-end-
Co-authors with Zhang of the paper, "Large cardiac-muscle patches engineered from human induced-pluripotent stem-cell-derived cardiac cells improve recovery from myocardial infarction in swine," published in the journal Circulation, are Ling Gao, Ph.D., Wuqiang Zhu, M.D., Ph.D., Saidulu Mattapally, Ph.D., Yasin Oduk, Ph.D., Xi Lou, Ramaswamy Kannappan, Ph.D., Anton V. Borovjagin, Ph.D., Gregory P. Walcott, Ph.D., Andrew E. Pollard, Ph.D., Vladimir G. Fast, Ph.D., and Steven G. Lloyd, M.D., Ph.D., all of the UAB Department of Biomedical Engineering; Zachery R. Gregorich, Ph.D., and Ying Ge, Ph.D., Department of Cell and Regenerative Biology, University of Wisconsin-Madison; and Xinyang Hu, M.D., Ph.D., Zhejiang University, Hangzhou, China.

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:

Engineering a new cancer detection tool
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.
Engineering heart valves for the many
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.
Geosciences-inspired engineering
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.
Engineering success
Academically strong, low-income would-be engineers get the boost they need to complete their undergraduate degrees.
HKU Engineering Professor Ron Hui named a Fellow by the UK Royal Academy of Engineering
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.
Engineering a better biofuel
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.
Pascali honored for contributions to engineering education
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.
Scaling up tissue engineering
A team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A.
Engineering material magic
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.
Engineering academic elected a Fellow of the IEEE
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:

Engineering: An Illustrated History from Ancient Craft to Modern Technology (Ponderables 100 Achievements That Changed History Who Did What When)
by Tom Jackson (Editor) (Author), Tom Jackson (Editor)

From ancient aqueducts to soaring skyscrapers, explore engineering milestones over the centuries.


Combining engaging text with captivating images and helpful diagrams, renowned science writer Tom Jackson guides readers through the history of Engineering in the 7th installment of the groundbreaking PonderablesTM series.


Engineering is all around us. From our bridges, tunnels and skyscrapers, to our cars, computers and smartphones, engineering shapes our world and influences just about everything we see and do. And it s been that way for longer than you might think.... View Details


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


101 Things I Learned in Engineering School
by John Kuprenas (Author), Matthew Frederick (Collaborator)

In this unique primer, an experienced civil engineer and instructor presents the physics and fundamentals that underlie the many fields of engineering. Far from a dry, nuts-and-bolts exposition, however, 101 THINGS I LEARNED® IN ENGINEERING SCHOOL probes real-world examples to show how the engineer's way of thinking can-and sometimes cannot-inform our understanding of how things work. Questions from the simple to the profound are illuminated throughout: Why shouldn't soldiers march across a bridge? Why do buildings want to float and cars want to fly? What is the difference between thinking... 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


Thermodynamics: An Engineering Approach
by Yunus A. Cengel Dr. (Author), Michael A. Boles (Author)

Thermodynamics, An Engineering Approach, eighth edition, covers the basic principles of thermodynamics while presenting a wealth of real-world engineering examples so students get a feel for how thermodynamics is applied in engineering practice. This text helps students develop an intuitive understanding by emphasizing the physics and physical arguments. Cengel and Boles explore the various facets of thermodynamics through careful explanations of concepts and use of numerous practical examples and figures, having students develop necessary skills to bridge the gap between knowledge and the... View Details


Materials Science and Engineering: An Introduction
by William D. Callister Jr. (Author), David G. Rethwisch (Author)

Building on the extraordinary success of eight best-selling editions, Callister's new Ninth Edition of Materials Science and Engineering continues to promote student understanding of the three primary types of materials (metals, ceramics, and polymers) and composites, as well as the relationships that exist between the structural elements of materials and their properties. This edition is supported by a redesigned version of Virtual Materials Science and Engineering (VMSE). This resource contains interactive simulations and animations that enhance the learning of key... 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


Irresistible: The Rise of Addictive Technology and the Business of Keeping Us Hooked
by Adam Alter (Author)

“One of the most mesmerizing and important books I’ve read in quite some time. Alter brilliantly illuminates the new obsessions that are controlling our lives and offers the tools we need to rescue our businesses, our families, and our sanity.” Adam Grant, New York Times bestselling author of Originals and Give and Take

Welcome to the age of behavioral addiction—an age in which half of the American population is addicted to at least one behavior. We obsess over our emails, Instagram likes, and Facebook feeds; we binge on TV episodes... View Details


Fundamentals of Engineering Thermodynamics
by Michael J. Moran (Author), Howard N. Shapiro (Author), Daisie D. Boettner (Author), Margaret B. Bailey (Author)

Fundamentals of Engineering Thermodynamics, 8th Edition by Moran, Shapiro, Boettner and Bailey continues its tradition of setting the standard  for teaching students how to be effective problem solvers. Now in its eighth edition, this market-leading text emphasizes the authors collective teaching expertise as well as the signature methodologies that have taught entire generations of  engineers worldwide.       

Integrated throughout the text are real-world applications that emphasize the relevance of thermodynamics principles to some of the most critical... View Details


Basics of Mechanical Engineering
by R K Singal (Author), Mridul Singal (Author), Rishi Singal (Author)

Basics of Mechanical Engineering systematically develops the concepts and principles essential for understanding engineering thermodynamics, mechanics and strength of materials. This book is meant for first year B.Tech students of various technical universities. It will also be helpful for candidates preparing for various competitive examinations. In Basics of Mechanical Engineering Each chapter includes problems selected from university examination papers and question banks. Exhaustive question bank on theory problems at the end of each chapter. Includes all supplementary material required... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Big Five
What are the five biggest global challenges we face right now — and what can we do about them? This hour, TED speakers explore some radical solutions to these enduring problems. Guests include geoengineer Tim Kruger, president of the International Rescue Committee David Miliband, political scientist Ian Bremmer, global data analyst Sarah Menker, and historian Rutger Bregman.
Now Playing: Science for the People

#456 Inside a Conservation NGO
This week we take a close look at conservation NGOS: what they do, how they work, and - most importantly - why we need them. We'll be speaking with Shyla Raghav, the Climate Change Lead at Conservation International, about using strategy and policy to tackle climate change. Then we'll speak with Rebecca Shaw, Lead Scientist at the World Wildlife Fund, about how and why you should get involved with conservation initiatives.