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Growing Artificial Organs
WALL-E, Walt Disney Pictures.
In 1954, the first successful organ transplant was performed by Drs. Joseph Murray and David Hume. A kidney was transplanted from one twin to his identical brother1. As of today, there are over 123,000 people in the U.S. waiting on organ transplant lists2. An organ transplant is required when one of your organs shuts down or fails as a result of illness or injury. The most commonly transplanted organs include kidney, liver, heart, pancreas, lung, and small intestine. With problems of transplant rejection (which we discussed previously) and limited organ availability, wouldn’t life be so much easier if we could swap parts like the robots in WALL-E? We might be getting closer and closer to transitioning from science fiction to reality.
The demand for organ transplants is on the rise.
In 2006, it was announced that the very first lab-grown organ, a bladder created from a patient sample, was successfully implanted in 19994. Years later, several other organs and tissues have been created, including windpipes, urethras, hearts, livers, lungs, and thymii (although most of these were not fully functioning). Scientists began by experimenting with different types of stem cells and placing them on material that served as scaffolding for support.
Takebe et al. took things a step further by creating tiny livers with a few different cell types: pluripotent stem cells that differentiated into the endoderm or spongy bulk of the liver; mesenchymal stem cells that became the connective tissue; and human umbilical cord blood cells that became blood vessels. This technique was valued because it more closely mimicked what occurs during normal, fetal development. These liver buds were placed inside mice, which quickly attached and began to form new arteries and veins. After 10 days, they even began to produce human liver proteins. When challenged with medications, the livers were also capable of metabolizing them and creating by-products. When transferred into mice with liver failure, the transplants increased their survival rates5.
Wouldn't it be useful if we had a check liver light just like we have a check engine light for cars?
The first "fully-functioning" lab-grown organ was touted in 2014 with the creation of a mouse thymus. This thymus was created from mouse fibroblasts that had been reprogrammed with FOXN1 and differentiated into induced thymic epithelial cells (iTECs). These iTECs promoted development of CD4+ and CD8+ T cells. The artificial thymus was then tested in vivo by being grafted onto a mouse’s kidney. After four weeks, the thymus was well-formed with a defined cortex and medulla region and was capable of producing different types of T cells6.

Induced thymic epithelial cells (purple) were transplanted onto the
mouse kidney cells (pink). Image from the University of Edinburgh.

Ok…maybe it’s a little biased.
Even aside from organ transplantation, the creation of organs allows for their in-depth study and analysis. In 2013, Lancaster et al. created “mini-brains”. Using embryonic stem cells or adult skin cells, they were able to re-create the neuroectoderm, which develops into the brain and spinal cord. These cells were placed in gel, which provided a structure for the cells to grow on. Specialized areas of the brain developed, such as the cerebral cortex, retina, and in some instances, the memory-focused hippocampus. The scientists believe this represented the brain of a 9 week-old fetus. The brains didn’t grow any larger or more complex as there was no blood supply that could penetrate to the interior. Even so, these mini-brains allow scientists to study structural and developmental defects, and possibly neurological disorders like schizophrenia. You could even take cell samples from a patient, re-create a mini-brain, and isolate how their development might have been skewed7.
Despite the advances in this technology, we’re still likely decades away from using artificial organs in humans. And, one should consider some additional concerns, such as:
  • Screening: Is the base tissue/cells used to create the new organ diseased?
  • Money: Customizing your own organs won’t be cheap.
  • Organ failure: New organs could fail in humans or require time to adapt.
  • Ethical issues: Why should I give up smoking if I have a pair of back-up lungs waiting?

Even with the concerns above, it’s no wonder that the potential of artificial organs has generated numerous success stories8. Companies are also looking to harness this technology. You can listen to our podcast with Organovo, which utilizes 3D printers to create tissues. What are your thoughts on these potential new sources of organs? Let us know at techserv@biolegend.com.
References:
  1. Organ transplant history
  2. Organ transplant list
  3. WebMD
  4. First artificial organ
  5. Vascularized and functional human liver from an iPSC-derived organ bud transplant
  6. An organized and functional thymus generated from ​FOXN1-reprogrammed fibroblasts
  7. Cerebral organoids model human brain development and microcephaly
  8. Scientists growing livers, kidneys, ears in labs amidst organ shortage

Just when I thought I got the hang of science... WALL-E, Walt Disney Pictures.
Contributed by Ken Lau, PhD.
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