Release date: 2017-05-22
Last month, a study published in the Circulation Research magazine published by the American Heart Association, Dr. Jianyi Zhang (translated author of the study) and Minnesota at the University of Alabama at Birmingham (UAB) The team of Dr. Brenda Ogle of the University has developed a stem cell-based 3D printed "heart patch" that can repair heart damage [1]! The first author of the study was Dr. Ling Gao, a postdoctoral fellow at Dr. Zhang Jianyi, who graduated from Shanghai Jiaotong University.
Dr. Zhang Jianyi (right, studied at Shanghai Medical University, now Shanghai Medical College, Fudan University) and Dr. Brenda Ogle (left)
The "heart patch" is of course born to repair the heart. In some heart attacks, the patient's blood can't be pumped into the heart muscle, and the cardiomyocytes will "ischemily die". Even if the patient is rescued, a lot of myocardium The death of the cell still causes a "scar" on the heart, leading to impaired heart function. And our heart can't create new cells to repair scars. What is even more "bad" is that the dead heart muscle tissue will "trap" the surrounding muscles, causing the "scar" to slowly expand, laying aside no small safety hazards [2].
At present, heart disease has become the most deadly disease in both the United States and China. Every year, 360,000 people die from heart disease in the United States, and more than 3 million in China, with an average of 2 out of every 5 deaths. The case is due to heart disease [3]. In this context, some researchers have begun to study how to "manually and quickly repair the heart."
At present, the use of stem cells to treat diseases is already a very hot research direction, and myocardial repair is no exception. In the past, many scientists have tried simple methods of transplanting stem cells, but the proportion of successful differentiation and survival after stem cell transplantation is not high, and the functionality after transplantation and the ability to transmit electrical signals are lack of verification [1]. These two important points have made some progress in the new research.
First, the researchers performed a 3D scan of the extracellular matrix (ECM) of mouse myocardial tissue. The ECM is a network of polysaccharides and proteins distributed between the cell surface and the cells to connect the tissue structure and regulate tissue. And the role of cellular physiological activities. Based on the scan results, the researchers printed a "scaffold" that mimics the ECM of mouse myocardial tissue with biodegradable materials.
In particular, the scanning technique used in the study can accurately project points with a resolution <1 μm onto the printed material, so the printed "scaffold" is highly similar to the mouse's own ECM. And this is the first time that this scanning technology has been successfully applied to the manufacture of tissue engineering scaffolds.
With the "carrier" of the stent, our stem cells have a "spot", and a large number of stem cells are placed on the stent to form a true "heart patch." Stem cells are induced pluripotent stem cells (hiPSCs) reprogrammed from human cardiac fibroblasts. After being placed on the scaffold, they are induced to differentiate into myocardium in a 2:1:1 ratio of cells in normal tissues. Cells, smooth muscle cells and endothelial cells.
D: 3D printed stent; E: a cell-filled stent; both bottom right corners are partially enlarged
The patch thus produced is referred to as hCMP by the researcher. In vitro, the researchers observed that it can be "integrated with natural heart tissue" and the electrical signal transmission of the cells carried is also very smooth. In addition, the researchers confirmed that the 7-day survival rate of differentiated cardiomyocytes on the "scaffold" is comparable to the currently used Matrigel medium for cultured hiPSCs.
The survival rate of cells on different media varied, black diamonds were Matrigel medium, black squares were hCMP, black triangles were polyethylene glycol, and white triangles were bovine pericardium.
Next, the researchers selected a mouse model of myocardial infarction (MI) to test them into three groups, one with two hCMP treatments, one with two pure stents without cells, and one The group served as a blank control and did not receive any treatment. Both hCMP and pure scaffolds are placed in the site where the infarction has occurred, and the decellularized bovine pericardium (a layer of skin-like tissue enveloping the bovine heart, without any cells after decellularization, avoids interference with the experimental results) It is fixed in the infarction position to avoid movement.
The results showed that the "transplanted" cells accounted for approximately 24.5 ± 2.6% at 1 week of treatment and decreased to 11.2 ± 2.3% by week 4. Despite the significant decline, this ratio is still much higher than the proportion of myocardial cell transplantation studies reported in the past (from 6.9% to 2% in 3-4 days) [4].
On day 28, the researchers performed echocardiography on the mice to assess the recovery of impaired cardiac function. The mice in the MI+hCMP group were the best recovery group, two important parameters - the left ventricle Ejection fraction (representing the contractility of the myocardium, the greater the contractile capacity, the greater the ejection fraction, <50% for functional impairment) and the left ventricular short axis shortening rate (also the parameter for measuring ventricular contractility, <25%) The damage to the function was significantly higher than the other two groups; and the area of ​​the infarct was also significantly reduced.
B, C: left ventricular ejection fraction (B) and short left ventricle in normal mice, myocardial infarction (MI) mice, pure scaffolding MI mice, and MI mice implanted with hCMP (top to bottom) Comparison of axial shortening rate (C); D: staining of myocardial tissue sections (sequence from left to right with B, C), BP for bovine pericardium
For their research, Dr. Ogle said that the study is different from previous studies because the "patch" is based on the structure of natural heart tissue, advanced 3D scanning and printing technology, and its physics. The structure is very similar to the "native structure". Only this type of 3D printing is capable of achieving a resolution of 1 μm, "perfectly" simulating a "native structure." Together with induced pluripotent stem cells, the three types of cells required can be differentiated according to the researchers' requirements. This "ingenious" combination has made their experiments successful.
Dr. Ogle (right) and her students, Molly Kupfer (left), one of the participants in this study, presented the "Heart Patch"
“The heart is very complicated. At first we were embarrassed about the efficiency of this 'patch',†Dr. Ogle said. "But we were greatly encouraged when we saw that the cells were neatly arranged in the scaffold and that the electrical signals were transmitted completely and smoothly."[5]
Based on the current success, researchers have begun to develop larger “patchesâ€, and their next goal is to test in the heart of pigs because it is similar in size to human heart, which is a “heart patch†into the clinic. An important step.
Reference material
[1] Gao L, Kupfer M, Jung J, et al. Myocardial Tissue Engineering With Cells Derived from Human Induced-Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold [J]. Circulation Research, 2017: CIRCRESAHA. 116.310277.
[2] https://
[3] Chen Weiwei, Gao Runlin, Liu Lisheng, et al. Summary of China Cardiovascular Disease Report 2015. China Journal of Circulation, 2016, 31: 624-632.
[4] Nguyen PK, Riegler J, Wu JC. Stem cellimaging: from bench to bedside. Cell Stem Cell. 2014;14:431–444. doi:10.1016/j.stem.2014.03.009.
[5] https://twin-cities.umn.edu/news-events/3d-printed-patch-can-help-mend-broken-heart
Source: Singularity Network (micro signal geekheal_com)
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