“Disease in a dish” is a cutting-edge, stem cell-based strategy that allows researchers to study an individual patient’s cells in a laboratory dish. Traditionally, scientists interested in a particular disease have used a standard cell line that has been grown in the lab for years or a mouse model (if one exists) that has been engineered to mimic the disease. Although extremely valuable, these techniques have obvious limitations. Animal models never entirely reflect the actual human condition – they don’t capture the complicated interplay between an individual patient’s genetics and the environmental factors that might influence the development of the disease or that patient’s response to a new therapy.
Read below to find out how diseases in a dish are made, how they’re being used to study and treat disease and how Sanford-Burnham researchers are applying the technique.
How can a disease be created in a dish?
Disease in a dish harnesses the power of stem cells to self-renew (generate more cells in a dish) and to differentiate (become a wide variety of cell types). In the early days of stem cell research, investigators could isolate stem cells from pathological specimens of the brain or bone marrow, or even obtain stem cells from non-viable embryos that carried lethal diseases. More recently, a special kind of stem cell called an induced pluripotent stem cell (iPS cell) has made the process quicker, more efficient and broadened the range of diseases that can be modeled. To generate iPS cells, researchers introduce a few new genes to almost any type of adult cell, essentially reprogramming it into a “pluripotent” stem cell – an embryonic-like cell that now has the potential to self-renew and, upon addition of growth factors or chemicals, produce cells from different organs
Researchers can then use iPS cells generated from a patient to model that individual’s disease in a dish. To simplify, the process of making Alzheimer’s disease in a dish might look a bit like this: cells isolated from an Alzheimer’s disease patient (like skin cells) –> iPS cells –> differentiated brain cells –> Alzheimer’s disease in a dish. This technology gives scientists access to an endless supply of cells that theoretically carry all the genetic and molecular changes that caused the disease.
What diseases are being studied?
Scientists hope using iPS cells to make diseases in a dish will allow them to develop new therapies for many diseases. At the moment, groups around the world are using disease in a dish to study Alzheimer’s disease, Parkinson’s disease, bipolar disorder, schizophrenia, and other neuropsychiatric disorders; neuromuscular diseases such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and muscular dystrophy; Rett Syndrome, lysosomal storage diseases and other childhood maladies – just to name a few.
How could disease in a dish advance the development of new drugs?
Currently, patients enter the scene during the last stage of drug development – clinical trials. The disease-in-a-dish approach allows researchers to use patients’ cells at a much earlier stage. Once established for a particular disease, scientists can use these cells as a model to test drugs for efficacy and safety, long before a person is put at risk. Disease in a dish has been called a “virtual clinical trial”; it is one of the tools now being applied to the developing field of “personalized medicine”.
What are the challenges in using disease in a dish?
Variability – from cell-line to cell-line, lab to lab, disease to disease – is one of the biggest challenges in using the disease in a dish technique. There are several steps in the disease-in-a-dish process that introduce variability, making it difficult to exactly reproduce a person’s disease from one experiment to the next. Once iPS cells modeling a particular disease are generated, it’s not clear how well they will reflect the original patient’s history and whole-body environment. In addition, scientists are still hunting for the best molecular markers that will allow them to distinguish between normal cells and diseased cells in a dish. The search for markers relevant to the manifestation of complex diseases is perhaps the most challenging. For example, what marker or quality of a nerve cell in a dish can explain the dementia and memory loss seen in Alzheimer’s disease? However, we are just beginning to explore disease-in-a-dish technology; new advancements, time and funding will undoubtedly allow scientists to explore all the options and improve this technique, ultimately enhancing its utility for understanding the mechanisms underlying diseases, identifying drug targets and choosing the correct therapies for a given effect.
How are Sanford-Burnham scientists using this technique?
Researchers in Dr. Evan Snyder’s laboratory are hammering out some of the fundamental developmental processes that must be understood before scientists can take full advantage of disease in a dish. They are figuring out how to induce iPS cells into a number of the different cell types found in the brain and testing if these cells function like they do in a person. Eventually, these findings could be used to model many different neurological diseases. The team is presently placing these cells into drug screening platforms to search for targeted neurological therapies.
Dr. Jeff Price’s and Dr. Mark Mercola‘s laboratories are using disease in a dish to screen drugs for cardiotoxicity – a side effect that harms the heart (a common reason for pulling pain and weight loss medications off the shelf). Disease in a dish techniques allow these researchers to scale up their efforts, using many different combinations of cells and drugs. They can actually see heart cells beating in a dish and, using cutting-edge video technology, they can record and measure contractions before and after drug treatment. This information could eventually be used to more quickly inform the selection and development of safer drugs, ultimately saving many lives.
Scientists in the Conrad Prebys Center for Chemical Genomics (Prebys Center) are also using powerful microscopes to compare the differences between normal cells and diseased cells in a dish. With this information as the read-out, robotic arms look for compounds that reverse signs of disease in a dish. They precisely add hundreds of thousands of chemical compounds one-by-one to tiny quantities of cells in a dish containing more than a thousand tiny wells. Later, the winning compounds might be further developed into new therapies that can be tested in people.
Watch the clip below as Dr. Michael Jackson, Sanford-Burnham’s vice president of drug discovery and development, describes how the Prebys Center is using disease in a dish:
For more information, read “Diseases in a Dish Take Off” (Science, November 26, 2010) or watch video from Panel 1: Disease in a Dish – Will it Translate? at the 2010 Stem Cell Meeting on the Mesa (video by The Science Network).