How to Grow a Heart: Transforming Stem Cells Into Live Organs

 An embryonic stem cell can not only self-renew like all other stem cells, but its special capacity is to make all different kinds of cells.  Indeed, it can make blood, it can make nerve, it can make the whole pancreatic islet, the part of the part of the pancreas that makes the hormone insulin.  So if one thinks about the significance of that, that means the discovery in the last couple of decades of stem cells has provided us with a reagent, a tool that can make any tissue in the body.  It can make all of the skin, brain and nerve, what’s called the ectoderm of the body, the outside of our body.  It can make all of the tissues on the inside, the mesoderm, which includes blood, heart, kidney, muscle and bone.  And it can make the gut tube, the endoderm, the lung, the liver, the stomach, the pancreas, the intestine.  

So to emphasize this, I want to show you a movie, something we do with students in the lab where we take human embryonic stem cells that are growing in a dish and turn them into beating heart cells.  So a petri dish has a colony or clones of these human embryonic stem cells growing.  And the arrow shows they are under self-renewing conditions.  When those conditions are removed, the cells automatically begin to specialize.  Here there’s red, yellow, blue, and purple cells, but the ones I want to show you in the movie are human heart cells.   

A striking example of human embryonic stem cells becoming a particular kind of cell is presented with a very simple experiment.  Here we have human embryonic stem cells growing in a petri dish as colonies.  If we remove the conditions that allow them to self-renew, removing that arrow, they will begin to automatically specialize and you can see here, it’s demonstrated or indicated by red, yellow, blue and purple cells.  But I wanted to highlight one particular kind of cell that can form here, which is human heart cells.  

The movie shows these cells beating.  They’re a little tiny clump of cells beating just like a heart.  Here are four different examples of it.  It might remind you of Edgar Allen Poe’s story, The Telltale Heart, where he couldn’t stop the heart from beating under the floorboards.  Here, once we take these human ES cells, as we call them, in a dish making heart cells, they’ll beat for ever and ever.  Now, the trouble here is, we’re not making a heart.  I want to emphasize that we are making a tiny little clump of cells.  And so biologists have been thinking about, how could we use those beating human heart cells to actually make a real heart.  

Well, this picture shows the way we might go about doing that.  In this case, we’re taking a rodent, a rat heart, and removing all of the cells, leaving a kind of a ghost.  You see here the white ghost on the right, which is a de-cellularized rat heart.  So it just has the matrix, the kind of scaffolding for a heart, but there aren’t any beating cells there and it’s dead tissue.  We can seed that scaffold with human or mouse embryonic stem cells that have been turned into heart progenitors.  And they will go on then to form a beating heart.  Here you see this heart pumping away which has heart cells that are made from embryonic stem cells.  That’s the sort of the beginning of a field called bioengineering where we’re thinking about how we would make organs and then eventually, of course, transplant them into people.  

Directed / Produced by Jonathan Fowler and Elizabeth Rodd

Doug Melton, Co-Director of the Harvard Stem Cell Institute, on the new frontier in biotechnology: creating human organs.

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Yale scientists restore brain function to 32 clinically dead pigs

Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.

Still from John Stephenson's 1999 rendition of Animal Farm.
Surprising Science
  • Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
  • They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
  • The research raises many ethical questions and puts to the test our current understanding of death.

The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?

But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.

What's dead may never die, it seems

The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.

BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.

The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.

As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.

The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.

"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.

An ethical gray matter

Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.

The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.

Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.

Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?

"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."

One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.

The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.

"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.

It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.

Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?

The dilemma is unprecedented.

Setting new boundaries

Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."

She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.

Scientists see 'rarest event ever recorded' in search for dark matter

The team caught a glimpse of a process that takes 18,000,000,000,000,000,000,000 years.

Image source: Pixabay
Surprising Science
  • In Italy, a team of scientists is using a highly sophisticated detector to hunt for dark matter.
  • The team observed an ultra-rare particle interaction that reveals the half-life of a xenon-124 atom to be 18 sextillion years.
  • The half-life of a process is how long it takes for half of the radioactive nuclei present in a sample to decay.
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