Growing Organs ūüßę | Stem cells, Organoids and 3D Bioprinting | Cell Biology ūüĒ¨

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.

Incredibly after 
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
to learn more about human biology..

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