Posted on Oct 04, 2018, 8 p.m.
The Chimera embryos represent a controversial feat and key step towards life saving lab grown organs, proving that human cells can be introduced into non-human organisms, survive and grow inside a host animal, as published in the journal Cell.
Consider the possibility of a custom organ grown inside an animal rather than having to wait, hope, and rely on a donor in a biomedical advancement that has been a quandary for scientists hoping to address critical donor organs shortages. This brings that dream on step closer from being science fiction to reality with the Chimera creation revealed from an international team of researchers led by the Salk Institute.
Such hybrid experiments are currently ineligible for public funding within the USA and many other countries, making human-animal hybrid Chimeras previously out of reach. Public opinion has also greatly hampered creation of such hybrid organisms. Private donors were relied on for this Chimera project by the Salk team.
Ancient civilisations associated mythical Chimeras with God, thinking that chimeric forms largely guarded humans, such as the human-bird hybrids known as angels. In that sense it is what the Salk team hopes their human animal hybrids will one day do. Although it may sound controversial and weird this is an ingenious way to eventually solve a number of biological problems with lab grown organs.
Chimeras can be made in two ways: Introducing organs of one animal into another which is risky as the host immune system may reject the organ; OR begin at the embryonic level by introducing cells together and letting them grow together into a hybrid.
When stem cells were discovered as the master cells producing virtually any kind of body tissues they appeared to contain unlimited promise, but convincing stem cells to grow into the right kinds of tissues and organs can prove to be difficult. First the cells must survive in Petri dishes, scaffolds must be used to ensure the organs grow into the right shapes, and patients must undergo invasive procedures to harvest tissues needed to start the process.
The concept of using host embryos to grow organs seemed straightforward to the researchers at first, however it took over 40 collaborators and 4 years to figure out how to go about making a human-animal Chimera, building on prior Chimera research involving mice and rats that figured out how to grow a mouse pancreatic tissue inside a rat to successfully treat diabetes. The Salk team took this concept further using CRISPR genome editing tools to hack into mice blastocysts where genes were deleted needed to grow certain organs, when rat stem cells were introduced that were capable of making the organs those cells flourished. Resulting mice were observed to live into adulthood, some of which growing chimeric gall bladders made of mouse-rat cells even though rats do not have gall bladders.
Rat stem cells were injected into pig blastocysts, this experiment failed due to rats and pigs having such dramatically different gestation times and evolutionary ancestors. Pigs have notable similarity to humans, though they take less gestation time their organs look a lot like humans. Introduction of human cells into pigs without killing them had to be timed perfectly. 3 different type of human cells were used representing 3 different times. Naive pluripotent cells were discovered through trial and error not to survive as well as those that had developed a bit more. Cells timed just right injected into pig embryos survived, which were put into adult pigs that carried the embryos for 3-4 weeks before they were removed and analysed.
186 later stage chimeric embryos were created that survived, the team estimated each had about 1 in 100,000 human cells which is a low percentage and may present a problem for the method in the long run. Human tissues appear to slow embryo growth, organs grown from such embryos as they develop now at that percentage would likely become rejected by humans since they would contains so much pig tissues.
The team wants to investigate whether it is possible to increase the number of human cells the embryos can tolerate. Current methods are a start, but it is not clear if that hurdle can be overcome; it could take years using the process to create functioning human organs. However the method could be used sooner as a technique to study human embryo development and gain better understandings of disease; real time insights from such studies could be just as valuable as abilities to grow an organ.
This work is at early stages, and there are other steps to be taken, according to the researchers who call their controversial work a very intriguing breakthrough. One thing is certain, this work is bound to receive much attention and a lot of heated debate from different opinions as such work always does.
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