Friday, July 26, 2019

World’s First 3D Printed Hearts And Functional Beating Hearts Grown From Stem Cells

This is an update on the progress made.  The possibility is slowly becoming an operational reality.  I would also like to see a protocol that allows stem cells to be infused directly into damaged heart tissue with a successful outcome.
Scar tissue does get replaced naturally, but slowly.  How might this be made faster?  The process is already there naturally so this should be possible.
All good.

World’s First 3D Printed Hearts And Functional Beating Hearts Grown From Stem Cells

by Andrea D. Steffen 
July 12, 2019 
More than 25 million people suffer heart failure each year. In the United States, approximately 2,500 of the 4,000 people in line for heart transplants actually receive them. That means almost 50% of the people needing a new heart to keep them alive won’t get it. But now, scientists from Massachusetts General Hospital and Harvard Medical School have successfully grown a human heart from adult skin cells in a lab. In addition, researchers from Tel Aviv University have “printed” the world’s first 3D vascularized engineered heart using a patient’s own cells and biological materials. Their research may someday soon solve the shortage problem of hearts the world faces today.

Grow A Heart

“A partially recellularized human whole-heart cardiac scaffold, reseeded with human cardiomyocytes derived from induced pluripotent stem cells, being cultured in a bioreactor that delivers a nutrient solution and replicates some of the environmental conditions around a living heart.” 
(CREDIT: Bernhard Jank, MD, Ott Lab, Center for Regenerative Medicine, Massachusetts General Hospital) 
In the study done by the scientists from Massachusetts General Hospital and Harvard Medical school, they grew a heart using stem cells then shocked it with an electric current to bring it to life.

Here’s what they did:

73 donor hearts deemed unfit for transplantation were used. 
They took skin cells and turned them into pluripotent stem cells, the kinds of cells that can be specialized to any part of the human body, using messenger RNA. Then, they caused the stem cells to develop into two types of cardiac cells. 
The scientists stripped away cells on the donated hearts and replaced them with those transformed skin cells. 
Next, they mimicked the environment a human heart would typically grow within and infused the cardiac cells with a nutrient solution that facilitated growth. They left the cells there for two weeks.
After the two weeks, they shocked the hearts with electricity and it began beating. Furthermore, the tissue inside appeared to be well-structured and functional. 
The study has been published in Circulation Research.

The team of scientists wrote:

To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole-heart scaffolds with human induced pluripotent stem cell–derived cardiomyocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue and showed electrical conductivity, left ventricular pressure development, and metabolic function.

Their goal is to eventually grow an entire human heart that is capable of being transplanted.
Print A Heart

“A 3D-printed, small-scaled human heart engineered from the patient’s own materials and cells.” (Credit: Advanced Science. © 2019 The Authors.) The world’s first ‘printed’ 3D vascularized engineered heart by Tel Aviv University completely matches the immunological, cellular, biochemical and anatomical properties of the patient because it uses a patient’s own cells and biological materials.

Here’s what they did: 
First, a biopsy of fatty tissue was taken from patients. 
Then, the cellular and a-cellular materials of the tissue were separated. 
While the cells were reprogrammed to become pluripotent stem cells, the extracellular matrix (ECM), a three-dimensional network of extracellular macromolecules such as collagen and glycoproteins, were processed into a personalized hydrogel that served as the printing “ink.” 
After being mixed with the hydrogel, the cells were efficiently differentiated to cardiac or endothelial cells to create patient-specific, immune-compatible cardiac patches with blood vessels and, subsequently, an entire heart. 
Their findings were published in the journal Advanced Science.

“Concept schematic. An omentum tissue is extracted from the patient and while the cells are separated from the matrix, the latter is processed into a personalized thermoresponsive hydrogel. The cells are reprogrammed to become pluripotent and are then differentiated to cardiomyocytes and endothelial cells, followed by encapsulation within the hydrogel to generate the bioinks used for printing. The bioinks are then printed to engineer vascularized patches and complex cellularized structures. The resulting autologous engineered tissue can be transplanted back into the patient, to repair or replace injured/diseased organs with low risk of rejection.” (Credit: Advanced Science. © 2019 The Authors.) Prof. Tal Dvir of TAU’s School of Molecular Cell Biology and Biotechnology, Department of Materials Science and Engineering, Center for Nanoscience and Nanotechnology and Sagol Center for Regenerative Biotechnology, who led the research for the study, said:

This is the first time anyone anywhere has successfully engineered and printed an entire heart replete with cells, blood vessels, ventricles and chambers…This heart is made from human cells and patient-specific biological materials. In our process these materials serve as the bioinks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models. People have managed to 3D-print the structure of a heart in the past, but not with cells or with blood vessels. Our results demonstrate the potential of our approach for engineering personalized tissue and organ replacement in the future… At this stage, our 3D heart is small, the size of a rabbit’s heart. But larger human hearts require the same technology.

The use of “native” patient-specific materials is crucial to successfully engineering tissues and organs. Prof. Dvir said:

The biocompatibility of engineered materials is crucial to eliminating the risk of implant rejection, which jeopardizes the success of such treatments. Ideally, the biomaterial should possess the same biochemical, mechanical and topographical properties of the patient’s own tissues. Here, we can report a simple approach to 3D-printed thick, vascularized and perfusable cardiac tissues that completely match the immunological, cellular, biochemical and anatomical properties of the patient.

The researchers are currently planning on culturing the printed hearts in the lab and “teaching them to behave” like hearts; then they will transplant them into animal models. Prof. Dvir said:

We need to develop the printed heart further. The cells need to form a pumping ability; they can currently contract, but we need them to work together. Our hope is that we will succeed and prove our method’s efficacy and usefulness. Maybe, in ten years, there will be organ printers in the finest hospitals around the world, and these procedures will be conducted routinely.

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