ClevaLab, Basic Principles of Human Biology
Explained. The replacement of failing organs with lab-grown fully functional human organs is a challenging goal that science has yet to achieve, but recently significant advancements have
been made, that may one day make this possible. The biggest issue for organ transplantation is organ rejection. This is when the immune system of the recipient recognizes the new organ as foreign and starts to kill the cells like it would during an infection. To prevent organ rejection transplant patients need to take drugs to suppress their immune system, which leaves them vulnerable to infections and cancers.
Even with these drugs the average life of a transplanted organ is 12 years, so some patients will need multiple transplants in their lifetime. But if scientists could somehow grow a new organ from the patient's cells, there would be no need for immune-suppressing
drugs, and the organ should last them a lifetime. Scientists are working towards this
goal by studying how organs develop. In humans organs develop from pluripotent stem
cells in the embryo, called Embryonic Stem Cells, these cells have the potential to differentiate
into any cell type in the human body. As the embryo grows into a fetus these cells
multiply, differentiate, and organise themselves into mature organs. This process can be mimicked
in the lab by growing embryonic stem cells with specific growth factors to coax these cells
into organ-like structures, called organoids, or mini organs in a dish.
This is done with a 3D culture system where the cells can grow in three dimensions within a gel of extracellular matrix, like the one found outside cells in the body. Due to ethical issues with the use of human
embryos, this research is tightly regulated and funding is restricted internationally. This
led researchers to try to find alternatives. It was known that some organs like the intestines
can regenerate their whole lining in a matter of weeks, and it had long been accepted that adult
stem cells in these organs were the source of this ability. Once the location of these stem cells
was identified, they were isolated and grown with specific growth factors known to be involved
in intestinal development and it was discovered that these adult stem cells residing in the organs
could also develop into organoids. These organoids have the same cell types and structure as the
lining of the intestine. These adult stem cells are already committed to becoming intestinal lining
cells, so they will only make intestinal organoids.
Around the same time scientists had discovered
that they could create pluripotent stem cells by reprogramming adult cells with specific
growth factors. Instead of needing a biopsy of a specific organ, a fibroblast from a
skin biopsy can be used to make organoids of any organ type, including intestines, stomach, kidney,
heart, and brain. This also overcomes the ethical issues of using human embryonic stem cells, as
these induced stem cells can be used instead. An organoid size is limited to around
one millimeter because the nutrients can only diffuse across this small distance, whereas
organs have blood vessels that supply nutrients deep into the tissues. To be able to grow fully
functioning organs, researchers will need to find a way to create tissues and organoids complete with
blood vessels and use these to deliver nutrients. But advances are being made, and while still
only millimeters in size, a heart organoid can be grown that closely resembles a fetal heart,
with all the major cardiac cell types, small heart chambers, and a vascular network.
several days of culture they even start to beat. Organoids are also being used to advance many
other areas of science, such as drug testing, cancer research, infectious disease, developmental
biology, and regenerative medicine. Recently several research groups have used brain organoids to study
how SARS-CoV-2, the virus that causes COVID-19, can infect and kill brain cells. Which could
explain some of the neurological effects of COVID-19, such as loss of smell and brain fog.
Organoids give researchers access to human organs that are otherwise inaccessible, and they also more
closely reflect human biology than animal models. Another way scientists are trying to create
tissues and organs is with 3D bioprinting.
A 3D Bioprinter works much in the same way as a standard
3D printer, except that they use bioink made from living cells or organoids instead of plastic resin
and they are often printed into extracellular matrix gel. Researchers have 3D printed live
tissues of several millimeters thick complete with blood vessels. For heart tissues, blood vessels
or cardiac cells are loaded in different nozzles of the printer in a nutrient-rich gel and
are then printed in layers in a support gel where the blood vessels exactly match those of the
patient. The goal is to surgically transplant these tissues to repair damaged hearts and restore
function. This has been shown to work in mice, but is yet to be used in patients. So while we
can't grow fully functional human organs yet, the study of organ development using organoids
will give us a greater insight into if and how this could be achieved.
In the not too distant
future, scientists could be repairing organs with lab-grown or 3D printed tissues. We'll have to
wait and see if fully functional human organs can be grown in the lab. Thanks for watching, please subscribe now
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