Cardiac Muscle Patches Engineered w/Human Induced-Pluripotent Stem Cell Improve Infarct Recovery.
The paper to which I'll point in this brief post: Large Cardiac Muscle Patches Engineered From Human Induced-Pluripotent Stem Cell–Derived Cardiac Cells Improve Recovery From Myocardial Infarction in Swine (Ling Gao, Zachery R. Gregorich, Wuqiang Zhu, Saidulu Mattapally, Yasin Oduk, Xi Lou, Ramaswamy Kannappan, Anton V. Borovjagin, Gregory P. Walcott, Andrew E. Pollard, Vladimir G. Fast, Xinyang Hu, Steven G. Lloyd, Ying Ge, and Jianyi Zhang Cirulation 2018;137:1712–1730)
This week it was my privilege to attend an online lecture By Dr. Ying Ge, of the University of Wisconsin. I was drawn to the lecture because of her use of a Bruker 15 Tesla FT-ICR mass spec, and the related Bruker TIMS-TOF instrument. (The lecture was sponsored by Bruker.) Before the lecture, I fully confess to being unfamiliar with her work; but I am actively familiarizing myself with it now.
I have seen, probably, hundreds, if not thousands of lectures on mass spec, and I'm sure I'll always place this one near the top, comparable to a lecture some years ago in the same forum by Dr. Richard Caprioli during which, among neat tricks, he showed imagines based on the proteome of a whole mouse, and discussed the proteome of a person who died around the time of the American Civil war.
In Dr. Ge's lecture, she discussed the creation of human heart muscle tissue, generated by culturing human stem cells derived from human blood, and culturing them so as to produce human heart muscle, which was then implanted into pigs (which have a proteome in many ways the closest to human) which had induced cardiac infartions, heart attacks.
The lecture included a short video of the generated tissue beating like a human heart.
The guts of Dr. Ge's paper, again available on line, but the abstract covers what the whole thing is about.
Background:
Here, we generated human cardiac muscle patches (hCMPs) of clinically relevant dimensions (4 cm × 2 cm × 1.25 mm) by suspending cardiomyocytes, smooth muscle cells, and endothelial cells that had been differentiated from human induced-pluripotent stem cells in a fibrin scaffold and then culturing the construct on a dynamic (rocking) platform.
Methods:
In vitro assessments of hCMPs suggest maturation in response to dynamic culture stimulation. In vivo assessments were conducted in a porcine model of myocardial infarction (MI). Animal groups included: MI hearts treated with 2 hCMPs (MI+hCMP, n=13), MI hearts treated with 2 cell-free open fibrin patches (n=14), or MI hearts with neither experimental patch (n=15); a fourth group of animals underwent sham surgery (Sham, n=8). Cardiac function and infarct size were evaluated by MRI, arrhythmia incidence by implanted loop recorders, and the engraftment rate by calculation of quantitative polymerase chain reaction measurements of expression of the human Y chromosome. Additional studies examined the myocardial protein expression profile changes and potential mechanisms of action that related to exosomes from the cell patch.
Results:
The hCMPs began to beat synchronously within 1 day of fabrication, and after 7 days of dynamic culture stimulation, in vitro assessments indicated the mechanisms related to the improvements in electronic mechanical coupling, calcium-handling, and force generation, suggesting a maturation process during the dynamic culture. The engraftment rate was 10.9±1.8% at 4 weeks after the transplantation. The hCMP transplantation was associated with significant improvements in left ventricular function, infarct size, myocardial wall stress, myocardial hypertrophy, and reduced apoptosis in the periscar boarder zone myocardium. hCMP transplantation also reversed some MI-associated changes in sarcomeric regulatory protein phosphorylation. The exosomes released from the hCMP appeared to have cytoprotective properties that improved cardiomyocyte survival.
Conclusions:
We have fabricated a clinically relevant size of hCMP with trilineage cardiac cells derived from human induced-pluripotent stem cells. The hCMP matures in vitro during 7 days of dynamic culture. Transplantation of this type of hCMP results in significantly reduced infarct size and improvements in cardiac function that are associated with reduction in left ventricular wall stress. The hCMP treatment is not associated with significant changes in arrhythmogenicity.
My point here is that Dr. Ge is clearly an immigrant, as are clearly some of her students, a function of China sending us some of her best and brightest to enlighten and raise us up out of the dregs of ignorance.
There are zero members among the 50 members of the White Supremacist Party in the United States Senate, and Zero members of that same party in the Congress who are her intellectual equal.
Zero.
Not the child molester from Florida and his idiot gun toting racist apologist with whom he travels while she rambles about Jewish space lasers, not Kevin the Klansman, the insurrectionist Minority Leader, not Moscow Mitch, none of them.
Let me say that again: Zero.
They are all, 100% of these white people in the US Congress in the White Supremacist Party, and their token African American from South Carolina, who would be qualified to wash glassware in her lab.
Just saying, in anger...
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