Biomedical researchers are constantly trying to find answers in the lab for several health-related issues like organ shortages. One possible solution, at least in theory, is to grow tissues and organs in the lab. Recently, scientists from the renowned Salk Institute in San Diego, California announced a big step forward in this field: They made the first successful effort combining human induced stem cells into a large animal — a pig!
These hybrids are commonly known as chimeras, coming from Greek mythology where chimeras are creatures made up of multiple animals. For a scientist, a chimera is an organism that is made up of cells from different organisms. So when you read in the news that scientists made the first human-pig chimera, it is not necessarily what it may sound like. Understanding the actual science behind the news will help demonstrate how momentous this advancement is and yet how much more work there is left to do.
How did scientists get human cells inside a pig?
Stem cells are defined by two main characteristics: 1) they make more of themselves via cell division (proliferate) and 2) they can become any type of cell in the body (pluripotent). Embryonic stem cells (ESCs) are the ones most often surrounded by controversy. When you look at a textbook picture of a blastocyst, the mound of cells in the middle is called the inner cell mass (ICM).
The cells in ICM ultimately become the entire organism, but early on the ICM houses stem cells. At this point, these cells are “undifferentiated” meaning that they have not determined a cell fate. Depending on the messages they receive from surrounding cells and the environment, they will begin to change (differentiate) into specific types of cells (brain, heart, kidney, pancreas, skin, etc).
After a stem cell chooses a fate, they cannot naturally become a stem cell again. However, in 2006 Japanese researchers from Kyoto University identified conditions necessary to “reprogram” cells back into a stem cell-like state. These cells are called induced pluripotent stem cells (iPSCs). For researchers, one major benefit of this model is that differentiated cells (like skin cells) can be isolated from patients, transformed into iPSCs, and then used to model diseases and develop drugs. Since these cells are from the patient, the hope is that the patient’s body will also be less likely to reject them.
The best part is that iPSCs overcome the ethical complications of embryonic stem cells. This Nobel Prize winning discovery has great implications for regenerative medicine. Scientists and clinicians hope to use these cells to create tissues to repair or entirely replace those damaged in the body.
But how can scientists take the cells and turn them into an organ outside of the body? Truthfully, they can’t yet. They still need to understand more about the environmental signals that instruct cells to become a specific organ. One way scientists hope to possibly grow these organs and tissues is by using animals to provide the environment for the stem cells to develop. The work done by these Salk scientists is the first steps in the right direction.
What exactly did these scientists do?
The team first used rodent models to test their hypothesis. They were able to grow rat organs in a mouse to replace mouse organs that were missing! However, mice and rats have biological limitations when it comes to biomedical research. Rats and mice are similar but unfortunately, humans and rodents are not so growing human organs in a mouse is unlikely.
This is why scientists turned to pigs, which are more comparable to humans. In these experiments, they injected human iPSCs into pig blastocysts. Excitingly, they saw that these cells could incorporate with the ICM. Then the pig blastocysts were re-introduced to a female pig and embryos were examined. Unfortunately, these embryos were sickly and small. But the human cells were incorporated into cells that would eventually give rise to different organs! This is the first time scientists have successfully been able to do this with human cells in a large animal.
So when can we use this in modern medicine?
This is a huge accomplishment in biomedical research but there is still a long way to go. First of all, “incorporated cells” are different from a full and functional organ or tissue, which is the ultimate goal. Plus the success rate of even these experiments was low. Can these cells actually grow into a fully functional organ? Can scientists direct these cells to grow into specific organs? How similar will these resulting organs be to the patient’s organ? There are so many variables in play that still need to be understood going forward!
As always, exciting science and technology comes with heavy ethical and social questions. One major issue is that these chimeras are not naturally occurring so scientists must question if it is appropriate. This also opens up a whole new area of animal rights and welfare. Even now, for scientists to conduct any level of animal research on rodents or any other animal, there are strict guidelines that are tightly regulated. As science evolves these issues will be continuously reevaluated and questioned. None of these scientific or ethical questions have a single, simple answer. Even for scientists, these questions are complicated and hotly debated.
In the meantime, science will discover new insight and develop new technologies that will reshape research in ways we cannot even imagine. Only time will tell how these findings will shape modern medicine!