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.
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