Cardiovascular diseases are the leading causes of death and disability worldwide. We are dedicated to developing new therapies to help cardiac patients by identifying, testing, and moving new therapies towards clinical use. We study stem cell therapies to prevent heart damage and promote repair. We use biomaterials to increase cell retention, increase efficacy, and target activity
Damage to heart muscle one hour after ischemia-reperfusion. Large amounts of neutrophils have already infiltrated the damaged heart muscle. Our lab is working on new therapies to minimize the damaging effects of these cells.
Regenerative Medicine at Emory
Projects
Stem cells
A major limitation to using stem cells to treat patients with cardiovascular diseases is the loss of transplanted cells almost immediately after they are delivered. The cells are washed out of the heart by blood flow, killed by the immune system, or fail to engraft. We are researching bio-compatible materials to support and direct the cells after they are implanted in the body. We focus on adult derived cell types easily obtained from most heart patients.
Immune modulation
Stem cells have the potential to heal tissue in many ways. Regenerating heart muscle lost after a heart attacks is extremely complex because the structure of the muscle cells, blood vessels and interstitium is complex. Stem cells can help heal the heart in a different way by softening the severity of the immune response. The immune system is necessary to remove the damaged cells, but often accelerates out of control causing more damage than necessary. We research cell therapies to reduce the magnitude of the immune response by preventing neutrophil infiltration and activation.
Biomaterials
The environment of the damaged heart on a cellular level is very hostile. There may be limited nutrients, low oxygen levels, disrupted cytoskeleton, and inflammation. In collaboration with several researchers at Emory and Georgia Institute of Technology, we are investigating biomaterials to support and direct delivered stem cells to the heart. We pair paracrine acting cells with materials that allow diffusion of growth factors and cytokines from the stem cells to the damaged heart.
Cardiac delivery
We believe that biomaterials will be needed to help stem cells work for heart disease. Many of these materials begin in a liquid state and later solidify into a gel. This property makes them difficult to deliver to the heart without open heart surgery. We are developing, safe, effective and minimally invasive devices to deliver stem cells and other therapies embedded in biomaterials to the heart.
Lab
Neutrophils are the most common circulating white blood cell. The body can make 200,000,000,000 neutrophils a day (Kolaczkowska E, Nature Reviews Immunology, 2013). Neutrophils are designed to kill bacteria that infect the body, but can cause damage to the heart because they are attracted to the injured tissue. Below are pictures of healthy neutrophils isolated from peripheral blood
Stem cells delivered to the heart cannot survive. With our collaborator W. Robert Taylor, MD, PhD we work on a technique called encapsulation. The stem cells are surrounded by a protective capsule of alginate that keeps the immune system from killing the cells and the blood from washing them out of the heart. The cytokines and growth factors that the cells make are small enough to diffuse out of the capsule, while the cells are kept safely inside. In this confocal microscopic picture, the live cells are stained green, and the rare dead cells are red.
Neutrophils interact with mesenchymal stem cells normally in the bone marrow. The mesenchymal stem cells keep the neutrophils from activating and harming the bone marrow. We are researching ways to use this calming effect to treat patients after heart attacks. In these two movies, the small round cells are neutrophils that congregate and surround the larger, flat mesenchymal stem cells.
Lab Alumni
- Eric Shin, MD - Indiana University
- Kai Xu - Central South University, China
- Marina Zemskova, MS - University of Arizona
In the News
May 2021
Juline's paper was accepted into the Journal of Cardiovascular Transnational Research. Thanks to the Aronov foundation and the CTSA for funding this work. Congratulations!
April 2021
Michael's paper was accepted into ATVB. Congratulations!
January 2021
Our first collaboration with Yerkes Primate Research Center and COVID-19 is published in Cell. Turns out neutrophils are important in viral infections, too.
September 2020
Sydney Ginn passed her PhD qualifying exam!
July 2020
Natasja Hirabayashi passed her PhD qualifying exam!
June 2020
Sydney Ginn won in the category of best basic science poster presentation at the Division of Cardiology Research Day.
January 2020
The Levit lab received a seed grant from the Woodruff Health Science Center to perform single cell RNA sequencing of neutrophils in injured hearts.
December 2019
Michael Sayegh was awarded a pre-doctoral research grant from the American Heart Association.
November 2019
The Levit lab was awarded a subcontract from CorAmi LLC SBIR to study a device to deliver hydrogels to the heart.
November 2019
Michael Sayegh won prize for best basic science poster at the Emory University Department of Medicine Research Day.
September 2019
Juline and Michael successfully presented their PhD proposals.
August 2019
Kimberly Cooney was awarded a travel award from the Society of Leukocyte Biology for their meeting in September.
January 2019
Kimberly and Kai published their paper in the Journal of Leukocyte Biology: Xu, K., et al. (2019). "Adenosine from a biologic source regulates neutrophil extracellular traps (NETs)." Journal of Leukocyte Biology.
July 2018
The Levit lab was awarded an Innovation Grant from the American Heart Association to study cardiac lymphatics in a project entitled, “The role of lymphatics in cardiac transplant allograft dysfunction."
July 2018
The Levit lab was awarded an R01 from NHLBI for a project entitled, “The regulation of neutrophil extracellular traps (NETS) by adenosine in myocardial ischemia-reperfusion.”
May 2018
The Levit lab published their work in collaboration with Garcia Lab at Georgia Tech on hydrogel delivery to the heart in Circulation EP: Garcia, J. R., et al. (2018). "Minimally Invasive Delivery of Hydrogel-Encapsulated Amiodarone to the Epicardium Reduces Atrial Fibrillation." Circulation: Arrhythmia and Electrophysiology 11(5).
November 2017
"MSCs in Cardiovascular Health & Disease: The Role of CD73 and Adenosine" ISACB webinar. (webinar located under "Fall 2017")
October 2017
November 2016
Dr. Eric Shin was chosen for an oral presentation at the American Heart Association’s scientific sessions in New Orleans!
September 2016
Congratulations to the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory for being ranked the No.1 in U.S. News & World Report top undergraduate biomedical engineering program.
September 2016
June 2016
The Levitt basic science cardiovascular lab was awarded a second year of funding and mentorship from the Coulter Foundation to develop new methods to deliver hydrogels to the heart!
July 2016
We are happy to present our work at the American Heart Association’s Basic Cardiovascular Science conference in Phoenix, Arizona.
October 2015
Awarded seed grant “Engineered mesenchymal stromal cells for enhancing lymphangiogenesis as a therapeutic for osteoarthritis”
Publications
- Sayegh MN, Cooney KA, Han WM, Wang L, Strobel F, Hansen LA, Garcia AJ, Levit RD. Hydrogel Strategy to Augment Tissue Adenosine to Improve Hindlimb Perfusion. Arterioscler Thromb Vasc Biol. 2021.
- Hoang TN, Pino M, Boddapati AK, et al. Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. Cell. 2021;184(2):460-475.e421.
- Xu, K., et al. (2019). "Adenosine from a biologic source regulates neutrophil extracellular traps (NETs)." Journal of Leukocyte Biology.
- Garcia JR, Campbell PF, Kumar G, Langberg JJ, Cesar L, Deppen JN, Shin EY, Bhatia NK, Wang L, Xu K, Schneider F, Robinson B, García AJ, Levit RD. Minimally Invasive Delivery of Hydrogel-Encapsulated Amiodarone to the Epicardium Reduces Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology. 2018;11.
- Shin EY, Wang L, Zemskova M, Deppen J, Xu K, Garcia AJ, Tirouvanziam R, Levit RD. Adenosine production by biomaterial supported mesenchymal stromal cells reduces the innate inflammatory response in cardiac ischemia reperfusion. JAHA, 2018.
- Garcia JR, Campbell PF, Kumar G, Langberg JJ, Cesar L, Wang L, Garcia AJ, Levit RD. A minimally invasive, translational method to deliver hydrogels to the heart through the pericardial space. JACC:BTS 2017.