Tag: drug discovery

How Lab Grown Organs can Revolutionize Biotech

So many medical breakthroughs occur in mice, but how often does mouse-model research translate to humans?

We need a way to safely test the efficacy of treatments on humans. Lab grown organs may allow us to do this. Organ tissue is being artificially grown and used to advance medical technology on a number of different fronts.

Purpose of Lab- Engineered Organs:

  1. Organ transplants: Replacing an entire dysfunctional organs in a human’s body.
  2. Research: Testing medical technology treatments – drug discovery and medical device efficacy.
source: Nathan Langer, UPMC

Benefits of growing organs in the Lab

  1. Organ transplants:
    • There is a shortage of donor organs for transplant. People die everyday waiting for a heart, lung, kidney, or liver transplant.
    • For those patients that do receive a transplant, there is a risk that the body will reject the new, foreign organ. This requires lifelong immunosuppressive therapy post-transplant. If there was a way to grow organs for patients using their own cells, it would ensure a perfect match and eliminate these risks.
    • Making replacement organs for a patient from their own stem cells means the organ would be so compatible with their body that it would eventually become a part of their body and not have to be replaced.
  2. Research:
    • The drug discovery process requires time, effort, and energy to test on animal models to ensure safety and efficacy before testing on humans. However, animal models don’t always translate to humans. Being able to test medical treatments on engineered human cells and tissues would accelerate this process and ensure greater safety.
    • Create a more humane research process by not needing to test on animals.

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Successful Progress Growing Organs

  • Today, we can successfully produce more simple organ structures in a lab (including arteries, tracheas, bladders). People have benefitted from lab-grown bladders and tracheas, for example. [1]
    • In dialysis, often blood vessels have to be replaced. Human cells will grow around artificial implanted blood vessel to form a new one. [4]
    • We can grow arteries from stem cells [5]
  • Researchers have uses 3D printing to create scaffolds in which stem cells grow into the shape of the organ. However, we are not able to connect the network of blood vessels, nerves, and more to the organ, so it remains as a group of non-functioning cells.

Challenges Growing Cell Groups:

  • To grow in three dimensions, cells need some sort of scaffold, which must be accepted by the body and ideally degrade over time into nontoxic components. [3]
  • It’s easy to grow cells in a Petri dish – I did this in college with prostate cancer cells. The challenge comes when trying to build more complex tissues – lab grown cells are quick to die when they get larger than about half a centimeter. There are no blood vessels going through the cells to supply them with nutrients.
  • “But without cues provided by blood flow and interactions with other tissues, the result would be simply a stomach-shaped statue, unable to digest or growl. An organ is much more than a mass of cells arranged in a particular configuration: it also has support scaffolds, blood vessels to deliver nutrients and signal molecules, and a hierarchy of intricate control functions that can respond to internal and external cues.” (2)
  • Livers, hearts, and tissues are complex tissues, hard to make.

Lab-Grown Cells for Medical Research

One method to test the efficacy of drugs during the development pipeline is by building small groups of cell components that are structurally and functionally similar to part of a human organ.

organs on chips
source: Wyss Institute, Harvard

These are called “organs on chips”, and allow researchers to simulate cells in the human body for drug development, disease modeling, and personalized medicine. [6]

The opportunity for this approach to bring transformational improvements in the field of personalized medicine cannot be overstated.

What are Organs on Chips?

The Wyss Institute, affiliated with Harvard University, is leading the development of a breathtaking medical technology called Human Organs-On-Chips.

The project allows small units of human organ tissue to be grown on polymer “chips” that recreate the biochemistry function and response of the cells in our organs. The cells are thus able to grow in realistic arrangements. Additionally, mechanical simulations applied to the chips allow the cells behave as they would naturally in human organs. By creating an environment that mimics the way cells feel and act in the human body, researchers are able to better understand and predict what is going to happen when medicines are given to humans.

Why is this a better technology than what currently exists?

Organs on Chips help to make the drug discovery process more effective and efficient. This helps solve a big problem in medical research. Currently, we test drugs in two general ways, either in petri dishes, or on animals. 

But these two methods of testing during of the drug discovery process are imperfect: 

  • The cells in petri dishes don’t behave exactly the way they do in a living being.
  • Animal trials fail to predict exact drug response in an actual human.

Organs on chips better mimic the microbiology of a human. By building simulations that closely resemble the way cells respond to medicine in the human body, medical researchers can find new drugs more effectively.

Designing Organs on Chips:

The chip itself is made of a clear flexible polymer. It is translucent so that we can see through the walls of the structure and observe what is happening among the human cells on the chip. 

By attaching the chip to various tubes and sensors, we can simulate blood flow to create a dynamic environment that brings in nutrients and removes waste products.

The chip has hollow microfluidic channels lined by living human organ-specific cells interfaced with a human endothelial cell-lined artificial vasculature.

Since cells are able to grow naturally with features like capillaries that allow blood flow to and from the cells, they behave naturally – the way they would inside our bodies. 

Simulating human living cells:

The chips don’t recreate entire organ systems, but small components that are of interest to medical research. They feature three-dimensional cross-sections of these major functional units within human organs.

The chip has mechanical forces that can be applied to mimic the physical microenvironment of living organs. These mechanical forces can vary in type and intensity.

They can be applied to a wide variety of cell / organ types to simulate the specific environment that occurs at that location.

For example, the mechanics of a chip can simulate breathing motions that occur in the lung, or the digestion process by creating peristalsis like deformations of the intestine cells.

Researchers have been able to line the chip with diseased cells from an individual patient, and the cells retain the features of the patient’s cells (becoming inflamed, etc.).

Personalized medicine:

We can personalize drug testing by placing individual patient cells inside these chips. To do so, we take the individual’s stem cells and grow them into the desired type of organ cell.

This helps researchers discover the dynamic response in the individual’s body to the drug during mechanically simulated but realistic cell behavior.

The differentiated behaviors of one’s cells compared to a control group allows researchers to understand how these cells function within the unique micro environment of that patient as an individual.

Chip linkages as organ systems

The ultimate goal of organs on chips is to recreate a small functional unit of a human organ, not entire organs. But these organ chips can be linked together.

By linking multiple chips together, for example cells from your heart, along with those from your lung and even digestive tract, researchers can take a more holistic approach to medical research and drug discovery, better understanding how a drug might affect your body as a whole.

This may even help discover and mitigate unwanted side effects.

Why does this matter?

Organs on chips are an exciting medical technology.

They will improve the accuracy and efficiency of preclinical testing for medicines, since they allow researchers to understand how living human organ cells respond to drugs and other treatments.

Medical research can continue developing organ-specific drug delivery systems. 

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Companies working on this:

Volumetric: trying to work our lungs. Air sacs are hard. Tissue-level, then organ-level therapies.

Sources:

  1. https://scholar.google.com/scholar?q=lab+grown+organs&hl=en&as_sdt=0&as_vis=1&oi=scholart#d=gs_qabs&u=%23p%3DHLvxb-jf3B4J
  2. https://scholar.google.com/scholar?q=lab+grown+organs&hl=en&as_sdt=0&as_vis=1&oi=scholart#d=gs_qabs&u=%23p%3Do2sO4BReRVgJ
  3. https://scholar.google.com/scholar?q=lab+grown+organs&hl=en&as_sdt=0&as_vis=1&oi=scholart#d=gs_qabs&u=%23p%3DPCbmXk2F4QgJ
  4. https://stm.sciencemag.org/content/11/485/eaau6934
  5. https://www.pnas.org/content/116/26/12710
  6. The Wyss Institute of Harvard