COVID-19 was initially identified as a respiratory disease, but scientists now appreciate that it also affects several other organs in the body, including the heart. Heart damage is a major determinant of COVID-19 related deaths, and even patients who experience only mild COVID-19 symptoms exhibit signs of cardiac dysfunction several months after recovery.
A new study by scientists at Gladstone Institutes helps explain how SARS-CoV-2, the virus that causes COVID-19, inflicts damage on heart cells. The team’s findings, shared publicly on bioRxiv, show the virus’s unexpected effects on the structure of heart cells in the lab, as well as in heart tissue from COVID-19 patients.
The team, led by Gladstone Senior Investigators Todd C. McDevitt, PhD, and Bruce R. Conklin, MD, was uniquely positioned to tackle this work, due to their experience in deriving various types of cardiac cells in the lab from induced pluripotent stem cells… Continue reading.
It’s well-known that COVID-19 affects the respiratory system, infecting healthy lung cells with the COVID-19 virus, but if it spreads to the heart it could become a much more deadly disease. A recent study found that in more than 10 percent of COVID-19 cases where heart damage occurred, there was no history of cardiovascular disease. Furthermore, a blood marker for heart damage (troponin) was the single best predictor of death, suggesting that heart damage is a key factor in mortality. Now the virus has been found in heart tissue, and the virus can infect human heart cells in a dish, stopping them from beating. Investigating the link between COVID-19 and damage to the heart is vital to preventing cardiovascular effects in future patients and perhaps finding a treatment for COVID-19 induced heart failure.
Senior Investigators Bruce Conklin, MD, and Todd McDevitt, PhD, are investigating how COVID-19 might damage the heart by asking two questions: How susceptible are the cells in the heart to infection by the virus, and what pharmaceuticals could be used to lessen damage to the heart or prevent the virus from infecting heart cells altogether… Continue reading.
Model organs grown from patients’ own cells may one day revolutionize how diseases are treated. A person’s cells, coaxed into heart, lung, liver, or kidney in the lab, could be used to better understand their disease or test whether drugs are likely to help them. But this future relies on scientists’ ability to form complex tissues from stem cells, a challenging undertaking.
In their natural environment, stem cells form predictable patterns as they mature; over time, these patterns morph into the tissues of an adult organism. In the lab though, researchers have struggled to control the spatial organization of stem cells–an important step toward being able to create functional organs for research or therapeutic purposes. Some have turned to 3-D printing to lay out populations of stem cells in a desired shape. But the approach isn’t always successful, with cells often migrating away from their printed locations… Continue reading.
The 10 graduate students are discussing stem cell population analysis, when it’s time. Before they can continue the discussion, Todd McDevitt, the instructor, has to do one thing — turn on the TV.
“That’s the beauty of this class, not only is the topic of stem cell engineering unique, but thanks to video conferencing technology, Georgia Tech students can now take a class with their peers from across the country,” said McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering.
Stem Cell Engineering (BMED 8813) has been offered since the spring of 2011 and was created by McDevitt as a way to educate graduate students about a research area that is becoming increasingly popular.
Including the 10 students at Tech, there are 39 students enrolled in this semester’s course. Aside from Tech, they are located at Washington University, the Massachusetts Institute of Technology, Boston University, University of California, Merced, and the University of Wisconsin. And although this is a graduate-level course, undergraduates can take the course with McDevitt’s permission.
So what can students expect during a week of classes? On Tuesdays, students from all of the participating campuses hear a lecture via the video conferencing system on a stem cell engineering topic — think everything from stem cell biology basics to stem cell biomanufacturing.
Tissue Engineering & Regenerative Medicine International Society – hosts an annual conference which is often found to be eye-opening by many people in the field of tissue engineering as it showcases the field’s latest technologies and groundbreaking research. This year, TERMIS-Americas is hosted by The Parker H. Petit Institute for Bioengineering and Bioscience at Georgia Tech with Dr. Robert Guldberg as the Conference Chair and Dr. Todd McDevitt as the Scientific Program Chair. According to McDevitt, the scientific program is ”based upon the fundamental principles, emerging strategies and applications of the latest advances in tissue engineering and regenerative medicine” along with “workshops and symposia on clinical and commercial translation.” There are 200 oral presentations and 400 poster presentations. Many of the presenters hail from foreign countries such as Japan and the United Kingdom. Since tissue engineering is a multi-disciplinary field, project creation involves everything from mechanical engineering to nanotechnology.
Researchers are now reporting advances in these areas by using gelatin-based microparticles to deliver growth factors to specific areas of embryoid bodies, aggregates of differentiating stem cells. The localized delivery technique provides spatial control of cell differentiation within the cultures, potentially enabling the creation of complex three-dimensional tissues. The local control also dramatically reduces the amount of growth factor required, an important cost consideration for manufacturing stem cells for therapeutic applications.
The microparticle technique, which was demonstrated in pluripotent mouse embryonic cells, also offers better control over the kinetics of cell differentiation by delivering molecules that can either promote or inhibit the process. Based on research sponsored by the National Institutes of Health and the National Science Foundation, the developments were reported online July 1 in the journal Biomaterials and were presented at the 11th Annual International Society for Stem Cell Research meeting held in Boston June 12-15, 2013 .
“By trapping these growth factors within microparticle materials first, we are concentrating the signal they provide to the stem cells,” said Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “We can then put the microparticle materials physically inside the multicellular aggregate system that we use for differentiation of the stem cells. We have good evidence that this technique can work, and that we can use it to provide advantages in several different areas.”
Georgia’s research university community recently welcomed Francis Collins, director of the National Institutes of Health (NIH). Collins met with administrators and researchers from the Georgia Institute of Technology, Emory University, the University of Georgia (UGA), Georgia State University and Morehouse School of Medicine during his May 30 visit to Atlanta.
Research university representatives highlighted NIH-funded projects. Scientists representing Georgia Tech included Robert Guldberg, executive director of the Petit Institute for Bioengineering and Bioscience and mechanical engineering professor, and Todd McDevitt, director of the Stem Cell Engineering Center and associate professor in biomedical engineering.
Guldberg shared information about the Regenerative Engineering and Medicine Center, a partnership between Emory University and Georgia Tech focused on endogenous repair and healing of nerves, bone, metabolic and cardiac applications. McDevitt presented four projects funded by NIH including wound healing studies from a “Transformative Research Award,” a program developed to fund “high-risk, high-reward” science under the NIH’s Common Fund.
The reprogramming technique allows a small percentage of cells – often taken from the skin or blood – to become human induced pluripotent stem cells (hiPSCs) capable of producing a wide range of other cell types. Using cells taken from a patient’s own body, the reprogramming technique might one day enable regenerative therapies that could, for example, provide new heart cells for treating cardiovascular disorders or new neurons for treating Alzheimer’s disease or Parkinson’s disease.
But the cell reprogramming technique is inefficient, generating mixtures in which the cells of interest make up just a small percentage of the total volume. Separating out the pluripotent stem cells is now time-consuming and requires a level of skill that could limit use of the technique – and hold back the potential therapies.
To address the problem, researchers at the Georgia Institute of Technology have demonstrated a tunable process that separates cells according to the degree to which they adhere to a substrate inside a tiny microfluidic device. The adhesion properties of the hiPSCs differ significantly from those of the cells with which they are mixed, allowing the potentially-therapeutic cells to be separated to as much as 99 percent purity.
Researchers from the Georgia Institute of Technology and Emory University found that chromatin compaction is required for proper embryonic stem cell differentiation to occur. Chromatin, which is composed of histone proteins and DNA, packages DNA into a smaller volume so that it fits inside a cell.
A study published on May 10, 2012 in the journal PLoS Genetics found that embryonic stem cells lacking several histone H1 subtypes and exhibiting reduced chromatin compaction suffered from impaired differentiation under multiple scenarios and demonstrated inefficiency in silencing genes that must be suppressed to induce differentiation.
“While researchers have observed that embryonic stem cells exhibit a relaxed, open chromatin structure and differentiated cells exhibit a compact chromatin structure, our study is the first to show that this compaction is not a mere consequence of the differentiation process but is instead a necessity for differentiation to proceed normally,” said Yuhong Fan, an assistant professor in the Georgia Tech School of Biology.
Fan and Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, led the study with assistance from Georgia Tech graduate students Yunzhe Zhang and Kaixiang Cao, research technician Marissa Cooke, and postdoctoral fellow Shiraj Panjwani.
The five-year project focuses on developing biomaterials capable of capturing certain molecules from embryonic stem cells and delivering them to wound sites to enhance tissue regeneration in adults. By applying these unique molecules, clinicians may be able to harness the regenerative power of stem cells while avoiding concerns of tumor formation and immune system compatibility associated with most stem cell transplantation approaches.
“Pre-clinical and clinical evidence strongly suggests that the biomolecules produced by stem cells significantly impact tissue regeneration independent of differentiation into functionally competent cells,” said Todd McDevitt, director of the Stem Cell Engineering Center at Georgia Tech and an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “We want to find out if the signaling molecules responsible for scarless wound healing and functional tissue restoration during early stages of embryological development can be used with adult wounds to produce successful tissue regeneration without scar formation.”
In addition to McDevitt, Coulter Department associate professor Johnna Temenoff and Woodruff School of Mechanical Engineering professor Robert Guldberg are also investigators on the project.
New research presented on June 16, 2011 at the annual meeting of the International Society for Stem Cell Research (ISSCR) shows that systematically controlling the local and global environments during stem cell development helps to effectively direct the process of differentiation. In the future, these findings could be used to develop manufacturing procedures for producing large quantities of stem cells for diagnostic and therapeutic applications. The research is sponsored by the National Science Foundation and the National Institutes of Health.
“Stem cells don’t make any decisions in isolation; their decisions are spatially and temporally directed by biochemical and mechanical cues in their environment,” said Todd McDevitt, director of the Stem Cell Engineering Center at Georgia Tech and an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “We have designed systems that allow us to tightly control these properties during stem cell differentiation, but also give us the flexibility to introduce a new growth factor or shake the cells a little faster to see how changes like these affect the outcome.”
These systems can also be used to compare the suitability of specific stem cell types for a particular use.
“We have developed several platforms that will allow us to conduct head-to-head studies with different kinds of stem cells to determine if one type of stem cell outperforms another type for a certain application,” said McDevitt, who is also a Petit Faculty Fellow in the Institute for Bioengineering and Bioscience at Georgia Tech.