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Lab-Grown Organs -- It's not Science Fiction!

by Reyna Jones

Lab-grown organs are no longer the eccentric creation of science fiction. For Madeline Lancaster, growing mini-brains was an accident. While researching how the brain forms during development, Lancaster was growing neural stem cells, an undifferentiated cell type that gives rise to neurons and glial cells used for signaling in the brain. She claims, “When I put the cells in the culture dish, there was something wrong with the reagents that I was using. Rather than forming these nice flat rosettes, mine were forming these weird, floating balls. I thought they looked interesting, so I continued growing them.” Although these pea-size globules are not exact replicates of a typical brain, researchers have found that they mimic several fundamental characteristics of a human brain, having structures that resemble ventricles, choroid plexuses, cerebral cortices, retinas and meninges. These mini-brains, formally called cerebral organoids, are just one type of organoid that researchers are using to understand human disease.

Organoids are small clusters of tissue that form rudimentary versions of organs. Simply put, mini-organs. Organoids are grown in vitro, outside of a living organism in a lab, using special techniques that allow them to grow in three-dimensions. Prior to the development and use of organoids, researchers were primarily limited to two-dimensional cell cultures and animals (mice, for example) to model and study human disease.

Although inexpensive and well-established, growing cells in two-dimensional culture is not necessarily the best way to understand and model human disease. Life is three-dimensional; the cells in our bodies are not flat. In this respect, organoids offer a significant advantage as they reflect three-dimensional cell growth in humans.  

While researchers often use animal models to test the efficacy of a drug before human trials, there is no guarantee that a drug that is successful in an animal model will be successful as a treatment in humans. However, animal models are critical in researching human disease, as human experimentation is considered unethical.  Organoids may represent a solution to this problem --- they can be grown from human stem cells and can exist outside of the human body.  Therefore, researchers can experiment on human tissue in a safe way that may eventually reduce the need for animal models in studying human disease.

    An individual’s genetic makeup influences what drugs are most effective. Doctors and researchers are striving to come up with ways to determine the best treatment method for patients by taking their genetic variability into account. In theory, this approach to treatment, often called precision medicine, could improve health outcomes by efficiently fighting disease as well as decreasing the side-effects of medications. In a recent study published in Nature, researchers used organoids as “patient-specific models” for predicting patients’ responses to cancer treatments. The researchers tested various chemotherapeutics against patient’s tumor organoids, grown from tumor biopsy cells, and found that if a treatment did not work on a patient’s organoids, it did not work for the patient. However, if the treatment was effective against a patient’s tumor organoids, it worked for the patient almost 90% of the time. This is the first study to compare the effectiveness of a particular treatment in organoids to the efficacy of the treatment in a patient. This study has fascinating implications regarding the possibility of using organoids as model systems for precision medicine.

However, there are not only brain and tumor organoids. There are over a dozen different types currently used to replicate and study human disease, including pulmonary (lung) and thymus organoids.  

    Lung disease is the leading cause of death worldwide, killing approximately four million people every year.  Pulmonary organoids have the potential to become models to represent and understand lung diseases such as asthma, COPD (chronic obstructive pulmonary disease) and lung cancer, which are the most common lung-related illnesses that affect millions of people each year. Researchers at Columbia University Medical Center were the first to develop lung organoids that display branching airways and alveolar structures that allow for the exchange of oxygen and carbon dioxide to breathe. To test the functionality of these organoids, researchers infected lung organoids with respiratory syncytial virus (RSV) which can cause bronchiolitis with small airway obstruction in children.  They found that the diseased organoids imitate the response of human lungs infected with RSV. As lung organoids continue to evolve and become more analogous to the human lung through research, scientists hope to use these models to find new treatments for lung diseases.

    The thymus is a lymphoid organ that is located behind the breastbone and between the lungs that secretes the hormone thymosin to promote the development of T-lymphocytes, commonly referred to as T cells. T cells are white blood cells that help fight infection and disease. Researchers are particularly interested in their potential to fight cancer and have developed a method known as adoptive T cell immunotherapy, which uses specialized T cells to target cancer cells. In this process, T cells are extracted from the patient, manipulated to target cancer and then transfused back into the patient. However, this process takes time and only works for patients that have enough T cells to alter. If the patient’s immune system is too weak from battling cancer, there may not be enough T cells left to extract and modify for the treatment to work.

Less than a decade after the clinical use of adoptive T cell immunotherapy, researchers at UCLA found a faster, more efficient way to produce cancer-specific T cells by using artificial thymic organoids.  The T cells developed with organoids can potentially target cancer without targeting healthy cells. Thymic organoids may eventually be used to create a reserve of cancer-specific T cells, from stem cells or donated blood cells, that can be used to treat patients promptly.

There has been significant research on the development and functionality of organoids. However, they are not yet perfect replicates of human organs. With continued research, scientists will learn more about the endless possibilities organoids offer in understanding and treating human disease. To quote Ray Bradbury, “Science fiction is the art of the possible, not the impossible.” Growing organs is no longer science fiction, but a reality.