Heart damage "saviour" - extracellative | Science sub-journal cover paper

Source: Science Translational Medicine Recently, researchers from Harvard University's Wyss Institute for Bio-Inspired Engineering and John A. Paulson's School of Engineering and Applied Sciences uncovered the underlying mechanisms behind EV's healing ability, engobscienting EV not only to re-energate cells after a heart attack, but also to maintain cellular function in the event of a heart attack when oxygen is lacking.
, studies have shown that EVs may come from endothyste cells, which are richer and easier to maintain than stem cells.
results were published in Science Translational Medicine on October 14 in the form of a cover paper.
: Blood flow to the heart is blocked when a heart attack or myocardial infarction occurs.
The best way to treat a heart attack is to restore blood flow, but this process could actually do more damage to heart cells, known as ischemia-reperfusion damage (ischemia-reperfusion injury, IRI) or reoxygenation damage, which occurs when tissue resumes blood supply after a period of hypoxia.
" cells to isoemia refill damage involves a variety of mechanisms, such as calcium overload, oxidative stress, mitochondrial dysfunction and so on.
complex processes challenge the development of effective treatments that address each of these issues.
" said Dr. Moran Yadid, lead author of the paper.
Vascular endothride cells are present in perfusion tissue in large numbers, and as the "first responder" to hypoxia stress, they are directly connected to the physical cells and are therefore highly involved in the side secretion signals sent to the body's tissues, including the highly vascular heart.
similar to other cell types, endostrotes secrete EVs, such as exosomes, and deliver information in the form of proteins and RNA to the subject cells, such as myocardial cells.
EEV carries goods that directly protect the heart muscle during and after a heart attack (Source: Science Translational Medicine) Researchers hypothesical endothelial-derived EV (EEV) contain substances that directly protect the heart muscle.
to assess whether EEV's protein composition mediated this effect, they mapped the vascular EEV protein map.
" is that although these follicles are only 150 nm in diameter, they contain nearly 2,000 different proteins.
many of these proteins are associated with metabolic processes such as breathing, mitochondrial function, signals, and steady state in the body.
in other words, it is associated with many processes related to the heart's response to stress.
Therefore, we believe that exosomes are not therapeutic molecules, but a mixture of molecules and proteins that work together to help cells maintain a steady state in the body, cope with stress, change metabolic behavior, and reduce harm."
," Yadid said.
the identification of heart-protective-related proteins in EEV.
the cellular mechanisms of potential heart protection mediated by proteomics found in the EEV sample.
arrow indicates pathological pathology path, and blue arrow indicates reaction.
(Source: Science Translational Medicine) Next, researchers tested the effects of EEV on human heart tissue using a chip heart model developed by the Disease Biophysics Team at the John A. Paulson School of Engineering and Applied Sciences.
chip organ platform simulates the structure and function of natural tissue and allows real-time observation of human tissue damage and therapeutic effects.
, the researchers simulated myocardial infarction and reoxygenation on the chip heart that was injected and not injected with EEV.
source: Science Translational Medicine (above); Harvard University's Wyss Institute for Bio-Inspired Engineering (D) they found that in tissues treated with EEV, myocardial cells were better able to adapt to stress and withstand higher loads.
3 hours of oxygen restriction and 90 minutes of reoxygenation induced damage, and then measured the proportion of dead cells and the contraction of tissue.
results showed that heart tissue treated with EEV had half the dead cells of untreated tissue (Figure B below) and that the effects of EEV on heart tissue vitality were shown to be dose-dependent (E below).
, in tissues treated with EEV, low levels of LDH( an enzyme that indicates cell damage) are secreted (Figure D below).
source: Science Translational Medicine Recovery of tissue contraction after isoemia refill injury is a key factor in determining the prognosis of myocardial infarction and development as heart failure.
researchers further verified whether EEV contributes to the maintenance and recovery of isoemia refilling the shrinkage function after injury.
results showed that heart tissue treated with EEV contracted four times more than untreated tissue.
, damaged heart muscle cells treated with EEV showed a group of proteins that were more similar to those of undefined heart muscle cells than untreated cells.
, the researchers also observed that cells treated with EEV contracted even without oxygen.
"Our results suggest that EEV can partially protect myocardial tissue from compound oxygen damage by supplementing damaged cells with proteins and signaling molecules that support different metabolic processes, paving the way for new treatments," said Dr. Andre G. Kleber, a visiting professor of pathology at Harvard Medical School who was involved in the study.
"When a molecule, a target of the traditional model can not cure the disease, exosome cell therapy may be beneficial.
through EV, we are taking a shotgun approach to a range of drug targets.
," concluded Dr Kevin Kit Parker, who led the study.
: 1 s Reviving cells after a heart attack (Source: Harvard University Wyss Institute of Bio-Inspired Engineering) 2 s Moran Yadid et al. Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip. Sci.Transl. Med. (2020)