The primary goal right now is to use the organoids as disease models, but along the way I predict we are going to learn a lot about how the brain is formed.”

— Paola Arlotta, PhD

What will be the biggest medical breakthrough 10 years from now? How about in 20 years, or 50?


There could be any number of answers to these questions, and although we cannot predict exactly what will happen, we can be certain of this: the breakthroughs of the future depend on laying the right scientific groundwork today.


Researchers at the Harvard Stem Cell Institute (HSCI) are doing just that by pioneering better ways to study human health and disease. Nowhere is this more apparent than in our work with organoids: small, three-dimensional tissue cultures that model the complexity of organs.


HSCI researchers have determined the precise growth conditions in the laboratory that coax stem cells to self-organize, forming structures that resemble miniature organs composed of different cell types. Organoids can range in size, from less than the width of a hair up to five millimeters across.


There are potentially as many types of organoids as there are different tissues and organs in the body. HSCI researchers have been able to produce organoids that resemble the brain, kidney, lung, and intestine, and many more are on the way. 


This approach of modeling organs is giving scientists an improved understanding how organs form and grow, setting the stage for new insights on human development and disease. In 2017, HSCI scientists pushed organoid research forward in many areas, perhaps most notably in nervous system and and lung diseases.

Paola Arlotta, PhD shares her work on brain organoids.


Most of what we know about embryonic brain development has been learned by making observations in mice and other animal models, then extrapolating them to human biology. Now, brain organoids grown from human cells are opening a window to understanding some of the most elusive aspects of human development and disease. 


Brain organoids are a particularly powerful model for studying complex, intrinsically human characteristics or diseases. “Some of the most prominent neuropsychiatric or neurodevelopmental diseases of our time, such as schizophrenia or autism spectrum disorder, are uniquely human diseases,” says Paola Arlotta, PhD.


Arlotta’s laboratory has developed methods to grow brain organoids for long periods of time. That way, the cultures can achieve a greater complexity and maturity than what was possible before. These organoids contain thousands of cells and multiple types of brain cells that interact with each other in sophisticated ways, making them good models for studying how diseases affect communication among brain cells.


Brain organoids are also enabling insights into how the brain is formed during early embryonic development, a subject that has been studied for more than a century yet still puzzles scientists today. “The primary goal right now is to use the organoids as disease models, but along the way I predict we are going to learn a lot about how the brain is formed,” Arlotta says.

Carla Kim, PhD discusses her lung organoid research.


Stem cells hold great promise as therapeutic tools due to their unlimited capacity to divide and regenerate tissue, but some diseases might be caused by anomalies in stem cells themselves.


“For a long time, it’s been thought that lung diseases like emphysema could be caused by stem cell defects, but it has not been possible to test this idea,” says Carla Kim, PhD. “Now, we can create organoids from patient cells and conduct experiments to find out which specific cell types cause lung disease. If we are able to understand what goes wrong at the stem cell level, there could be a whole new cell type that could be targeted for therapeutic intervention.”


Kim and her group were the first researchers to grow lung organoids that model two distinct parts of the lung: the airways and the alveolar sacs where blood undergoes gas exchange. They developed a special culture setup that puts cells in contact with both air and liquid, mimicking the lung environment in humans. 


In addition to studying the causes of disease, organoids can also be used more directly to identify and test new drugs. For example, in cystic fibrosis, ciliated cells that normally remove mucus from the lung do not function properly.


“We are able to make organoids with ciliated cells derived from patient stem cells, and then test for drugs that might make the ciliated cells work better,” Kim says. “This is a very exciting time for studying the lung.”

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