The Jungle Book: Sheep Aid in Human Organ Tansplant(s)

INTRODUCTION: 

Researchers have now officially grown sheep embryos with the aid of human cells. Scientists say growing human organs inside animals could not only increase supply, but also offer the possibility of genetically tailoring the organs to be compatible with the immune system of the patient receiving them, by using the patient’s own cells in the procedure, removing the possibility of rejection. [A]

Every hour in the United States 6 people are added to the country’s national waiting list for organ transplants. Every day, 22 people on that list dies waiting for their transplant. For example, over 100,000 people need a heart transplant each year, but only 2,000 will get one. [B] Even in cases where the organs are a 'perfect' match (besides organs donated from an identical twin), do not last very long because the way the human immune system functions it is constantly attacking the organ because it thinks that it is a foreign object entering the body. [A] 

Researchers have been working to increase the number of organs artificially in lab. Some research teams are working with 3-D prints of organs in the lab. Others are studying and tinkering with artificial mechanical organs. The rest are producing ‘chimeras’ which are hybrids of two different species with the goal of growing human organs inside of pigs or sheep. [B]

Inspired by a controversial breakthrough made in 2017, scientists have created a second batch of successful human-animal hybrids: sheep embryos that have 0.01 percent human by cell count. The embryos have been approved by the board to develop to 28 days of age to help researchers in their efforts of growing human organs for medical transplant. [B]

 

BACKGROUND INFORMATION:

Chimeras are made by isolating 1 of the animal’s stem cells which can then develop into any type of cell in the body. Then, a few stem cells from one species is injected into the embryo of another. It is difficult/tricky to complete the procedure properly because if the embryo’s DNA is hacked so it doesn’t grow into a specific organ, the interloping cells would be the only ones filling in the gap. This is how researchers can grow a human liver inside of a living pig [B].

In 2017, researchers used this procedure to grow mouse pancreases in rats and revealed that transplants using the pancreas could cure diabetes in diabetic mice. Salk Institute researchers have stated that they can keep pig embryos injected with human stem cells alive for 28 days. Stem-cell experts lauded the human-pig study, but they noted that the pig embryos' counts of human cells—about one in a hundred thousand—were too low for successful organ transplants. [B]

When 'Dolly the Sheep' was created at the 'Animal Bio-Technology at Roslin Institute', the research happening today are working to discover if sheep can be one day a viable option for the ‘chimeric project'. The approach is different to 'xeno-transplantation' because the organ that is being transplanted into a human is from another species. But, tissue organ rejection is still possible. [A]

For quite some time, researchers and scientists alike have been attempting to grow organs from different species. A recent breakthrough has revealed to be a success when applying human stem cells into young pig embryos that allowed for the birth or production of embryos in which about 1 in every 100,000 cells were human.[A]

On this year’s, 2018, annual meeting of American Association for the Advancement of Science in Austin, Texas, researcher Pablo Ross and his colleagues from University of California, Davis, announced that they have fine-tuned the procedure—boosting human cell counts in sheep embryos to one in ten thousand. [B]

A research team from Austin, Texas announced their efforts for a similar breakthrough with sheep embryos that an even larger ratio of human cells to animal cells was observed. They stated to the ‘American Association of Advancement of Science’ that 1/100,000 cells in their sheep embryos were in fact human cells. [A]

In addition, this team has been able to apply genome editing techniques to produces pig and sheep embryos. These embryos, however, were unable to develop a pancreas. Work towards this is still ongoing. The hope is that the human cells introduced to such embryos would grow to replace the missing organ. [A]

About one percent of the embryo would have to be human for the organ transplant to work. In addition, extra steps are needed to prevent immune system from rejecting the organ to ensure that leftover parts of animal viruses stuck from the pig or sheep’s DNA. [B] 

Ross says that the research could be accelerated if it were better funded. As work continues, ethical scrutiny will also surely intensify. Ross and his colleagues acknowledge the controversial nature of their work, but they also say that they're moving cautiously. [B]

The contribution of human cells so far is very small. It’s nothing like a pig with a human face or human brain. researchers are trying to target where human cells proliferate, to ensure that they don't set up shop in animals' brains or sex organs. [B]

Ross, for one, sees the ever-widening approaches for organ research as cause for optimism. All these approaches are controversial, and none of them are perfect, but they offer hope to people who are dying on a daily basis. We need to explore all possible alternatives to provide organs to ailing people. [B] The team was granted permission to let the chimeric embryos develop for 28 days, 21 of these in sheep. While that might be sufficient to see the development of the missing organ when human cells are eventually combined with the genetically modified embryo, a longer experiment, perhaps up to 70 days, would be more convincing, (which would require additional permission from institutional review boards.) [A]

But, for the approach to work it is thought that about 1% of the embryo’s cells would have to be human, meaning further work is needed to increase the proportion of human cells in the chimera.

Ross added there are several advantages to using sheep embryos, including that they can easily be produced by IVF, and that fewer embryos need to be transplanted into an adult, meaning fewer embryos are needed for an experiment. For a pig, researchers have typically transferred 50 embryos to one recipient, but with sheep the transfer is 4 embryos to 1 recipient. [A] 

 

 

Anatomy speaking, sheep have similar organs to humans such as the heart and lungs and their embryos form chimeras with goat embryos to produce ‘geeps’ and like pigs, sheep produce organs of proper proportions or size to the human body. Research with pigs is continuing. The benefits observed in these studies includes speed of growth and ability to produce a greater number of offspring than sheep do, meaning fewer animals are needed to produce more data. [A]

RESEARCH:

The team are looking at where the human cells end up in the chimera. Some concerns exist whether this would produce chimeras with a human-like mind. But, many are optimistic about the future of receiving organs from animals. Others are not as concerned because the contribution of human cells has been very small. Many papers have been published that have revealed that the area can be targeted meanwhile avoiding human cells differentiating in to the human brain or human gonads. [A]

Other potential issues could arise like the viruses inside the Host DNA infect the human cells, while the human organ might contain blood vessels composed of cells from the “host” animal. Then in this case, these organs cannot be used for organ transplants without triggering the immune system’s defense against invaders and will reject the organ immediately. [A] 

CONCLUSION:

Recent developments in gene editing have allowed scientists to grow baby pigs/piglets without these viruses, while the human cells might replace any remaining host cells after transplantation.

Links:

[A] https://www.theguardian.com/science/2018/feb/17/breakthrough-as-scientists-grow-sheep-embryos-containing-human-cells

[B] https://news.nationalgeographic.com/2018/02/sheep-human-hybrids-chimeras-crispr-organ-transplant-health-science/
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