Recently, scientists at the National Center for Advancing Translational Sciences (NCATS) have partnered with the International Space Station U.S. National Laboratory (ISS National Lab) to do biomedical research -- in space.
Why? The microgravity environment serves as an ideal laboratory for studying aging and similar disorders, such as “muscle deterioration, osteoporosis (bone loss), reduced cardiopulmonary function and immune deficiency -- when in space have been documented…[and] reversible when astronauts return to Earth'' (NCATS, 2021). Since symptoms of aging can be studied in space, research on astronauts and organs in microgravity is novel because we can test and retest hypotheses more quickly, safely, and efficiently than if we were to experiment on seniors. Moreover, NCATS has introduced another secret weapon -- tissue chips.
Introduction
Researchers create tissue chips, or organs-on-a-chip, by various methods, but the most common way to do so is to host cells inside the chip and observe their reactions with each other. Instead of 3D printing blood vessels with plastic to look exactly like a heart, we can think of tissue chips as controlled little microscope slides that allow more than one type of cell to interact with other types of cells found in the same organ -- like a macho microscope slide. Usually, cells are obtained from a patient donating their cells when they are getting surgery for another reason. These cells are then genetically modified to create induced pluripotent stem cells, or iPSCs. Since they are stem cells, they can differentiate into different cells of the same organ, which are then transported inside the chip to interact with each other in a closed environment, simulating what it might look like inside an actual organ without having to cut up a body.
Implications
Tissue chips are about the size of your thumb, but their implications to biomedical research extend farther than you might imagine. Instead of printing out an entire organ or observing a real one inside a human, tissue chips are made by flexible plastic, designed to simulate an organ’s physiological responses to other organs and environmental stresses. From a lab-on-a-chip, which simulates a laboratory environment on a plastic chip, tissue chips also replicate laminar flow of blood, which is a unique phenomenon in cells where blood travels at the same velocity (no matter whether the blood is on the bottom versus the top). Before, 3D models were used to replicate cell differentiation. Tissue chips, however, address this problem by mimicking transport of nutrients, cell organization, and responses to changes in the entire body. Tissue chips are revolutionary because they give way for scientists to be able to easily simulate and observe organs without having to perform surgery on multiple patients. All the cells used are “recycled” from past surgeries, so it is non-invasive compared to other current research methods. Moreover, tissue chips can help screen drugs for possible side effects before giving them to humans, making testing more efficient, safe, and cheap.
Limitations
Tissue chips still are not at the stage to accurately represent the human organ, much like how animals are not the best way to replicate for human studies. Unlike animals, however, these tissue chips are actual human cells, and they can be observed with a microscope more easily than cutting a mouse open. As a result, tissue chips have much room for improvement than animal models. For example, many cells used today are propagated from iPSCs, but these cells may not replicate all the different types of cells in the human body. Additionally, before these cells are transplanted into the thin plastic, they undergo many processes to “clean” them using antimicrobial agents, which do not reflect normal organ processes. In the end, however, some scientists have been finding ways to replicate symptoms from asthmatic patients as well as people who have slower heart rates. This shows that current research is pointing in the right direction, and further research can expand how much we can replicate not only a generic organ but also a specific patient, opening doors for better individualized medical care.
For now, tissue chips provide a new gateway for drug and microbiological research, chipping away and uncovering new techniques for discovery.
For more information on different chips, we have compiled summaries from the National Center for Advancing Translational Sciences’ Chips.
Brain Chips
Scientists at the Morgridge Institute for Research in Wisconsin developed the brain tissue chip by differentiation a stem cell into different types of brain cells, from oligodendrocytes (helps neuron signal to each other in the central nervous system, producing the myelin sheath to make signals faster), glutamatergic neurons (regulating glutamate, an important neurotransmitter responsible for exciting cells, astrocytes (glial cells, meaning they provide nutrients, structure, and protection for neurons and are essential in the central nervous system), endothelial cells and pericytes (cells that line blood vessels), and GABAergic cells (neurons that use a neurotransmitter called GABA, responsible for inhibiting transmissions of action potentials in the central nervous system and important for preventing epilepsy, sleep disorders, tremor, etc.). With these cells in the same chip, they hope to replicate basic interactions inside the brain.
Moreover, a team at Vanderbilt University is attempting to replicate the blood-brain barrier on a chip by generating brain cells and blood vessels iPSCs from donor cells and organizing them in layers, acting like the blood-brain barrier, the vessels that give oxygen to neurons in the central nervous system.
Heart Chips
UC Berkeley has been developing the heart on a chip, generating cardiac cells from iPSCs, producing a tissue that can even replicate a heartbeat. From these stem cells, the researchers had some success in replicating characteristics of the organs from the adult donor, such as a slower heart rate.
Another research team from Columbia University, MIT, Boston University, the Wyss Institute at Harvard University and Yale University also try to integrate circulation into the heart tissue chip, so they may study the effects of drugs, genetic states, and diseases in the heart.
Lung Chips
At Harvard University, iPSCs were used in order to study asthma because lung smooth muscle cells that are not found in animal models. Further research can be done in improving the model as well as testing possible drugs on a healthy model versus an asthmatic model.
Liver Chips
A team at the University of Pittsburgh has created a liver on a chip with four cell types that were gotten from cancer patients who donated parts of their liver to the National Institute of Diabetes and Digestive and Kidney Diseases-funded Liver Tissue and Cell Distribution System. There were hepatocytes, the parenchymal (main functional) cell responsible for metabolism, detoxification, and protein synthesis, stellate cells and liver sinusoidal endothelial cells (LSCECs are blood vessels and stellate cells are in between endothelial and hepatocytes), and Kupffer cells (immune cells that also break down red blood cells). Luke Lee from UC Berkeley also is researching how to generate liver cells from iPSCs as well in order to combine their heart tissue chips with their liver tissue chips to screen for potential side effects with drugs.
Other Chips
Include kidney chips, the female reproductive system, skin, muscle, gastrointestinal tract, fat, blood vessels, and more.
