It’s the closest we've come to growing transplantable hearts in the lab
Of the 4,000 Americans waiting for heart transplants, only 2,500 will receive new hearts in the next year. Even for those lucky enough to get a transplant, the biggest risk is the their bodies will reject the new heart and launch a massive immune reaction against the foreign cells. To combat the problems of organ shortage and decrease the chance that a patient’s body will reject it, researchers have been working to create synthetic organs from patients’ own cells. Now a team of scientists from Massachusetts General Hospital and Harvard Medical School has gotten one step closer, using adult skin cells to regenerate functional human heart tissue, according to a study published recently in the journal Circulation Research.
Ideally, scientists would be able to grow working hearts from patients’ own tissues, but they’re not quite there yet. That’s because organs have a particular architecture. It's easier to grow them in the lab if they have a scaffolding on which the cells can build, like building a house with the frame already constructed.
In their previous work, the scientists created a technique in which they use a detergent solution to strip a donor organ of cells that might set off an immune response in the recipient. They did that in mouse hearts, but for this study, the researchers used it on human hearts. They stripped away many of the cells on 73 donor hearts that were deemed unfit for transplantation. Then the researchers took adult skin cells and used a new technique with messenger RNA to turn them into pluripotent stem cells, the cells that can become specialized to any type of cell in the human body, and then induced them to become two different types of cardiac cells.
After making sure the remaining matrix would provide a strong foundation for new cells, the researchers put the induced cells into them. For two weeks they infused the hearts with a nutrient solution and allowed them to grow under similar forces to those a heart would be subject to inside the human body. After those two weeks, the hearts contained well-structured tissue that looked similar to immature hearts; when the researchers gave the hearts a shock of electricity, they started beating.
While this isn’t the first time heart tissue has been grown in the lab, it’s the closest researchers have come to their end goal: Growing an entire working human heart. But the researchers admit that they’re not quite ready to do that. They are next planning to improve their yield of pluripotent stem cells (a whole heart would take tens of billions, one researcher said in a press release), find a way to help the cells mature more quickly, and perfecting the body-like conditions in which the heart develops. In the end, the researchers hope that they can create individualized hearts for their patients so that transplant rejection will no longer be a likely side effect.
The tricks of physics that cause organs to form
Stem cells, the jack-of-all-trades building blocks of human tissues, have yet another application in biology research: scientists have been able to grow them into beating cardiac tissue. This could help scientists better understand how the heart develops and test if drugs might be affect cardiac development in growing fetuses.
In a fetus, stem cells become heart tissue through a symphony of chemical cues, conducted by DNA. But the laws of physics also play a role—cells in the body get pushed and pulled into different positions, which changes how DNA regulates them.
In the study, published today in Nature Communications, the researchers started out with stem cells derived from skin tissue. In a petri dish, they used the growth medium typically used to coax cells to develop. But they added something new: a chemical layer that had different areas with tiny little etchings made with oxygen plasma. These slight physical and chemical differences in a the different areas of the dish caused the stem cells to develop into different types of cardiac tissue cells—just as they do in the human body. By day 20, the cells had formed heart “microchambers” that were actually beating, albeit slowly. This is a time-lapse of the tissues moving over a 24-hour period:
And here's a 3D reconstruction of the microchamber:
To see if other chemicals could affect these lab-grown tissues, the researchers dosed some of the cells with thalidomide, a drug known to affect heart development in fetuses. Just as the researchers expected, the microchambers didn’t develop properly.
This research could help scientists better understand how the heart develops. Most of their current knowledge and testing is based on mouse heart cells, which aren’t quite the same as in humans. Having beating heart tissue readily available in the lab could also make it easier for researchers to test how drugs can affect fetus hearts, which could lead to new drugs that are safer for pregnant women.
The researchers also note that similar tactics could help grow other kinds of organs in the lab as well.
A team of scientists from the University of Pittsburgh School of Medicine has created lab-grown human heart tissue that can beat on its own, according to a new study in Nature Communications.
In 2008, a University of Minnesota study showed that the original cells from a rat heart could be completely flushed out of the heart's external structure in a process called decellularization, then replaced by newborn rat cells to regenerate a working heart. A similar process has now allowed Pitt scientists to grow working human heart tissue within the decellurized structure of a mouse heart.
Using various enzymes and special cleansing detergents, the researchers stripped a mouse heart of all its cells to create a scaffold for induced pluripotent stem cells (iPS cells), adult human cells that are reprogrammed to act like embryonic cells. They treated the iPS cells taken from a skin biopsy to become multipotential cardiovascular progenitor (MCP) cells, the precursor cells that can become any of the three types of cells found in the heart.
"Noody has tried using these MCPs for heart regeneration before," said Lei Yang, an assistant professor of developmental biology at Pitt. After a period of a few weeks, the human cells had repopulated the mouse heart, and it began beating at a rate of 40 to 50 beats per minute. That's a little slow, though not by much. A typical resting heart rate for an an adult is between 60 and 80 bpm, though anything above 50 bpm is still considered normal.
This could eventually lead to personalized organ transplants, or even just a great way to study in the lab the way they human heart develops or how it responds to drugs.
Next, Yang wants to try to make just a patch of human heart tissue, which could be used to replace only regions of the heart that have been damaged by something like a heart attack. He told PopularScience.com via email that he hopes to test heart tissue patches in animals within the next few years.
The study came out in the Aug. 13 issue of Nature Communications.