Science’s Main Course? A Disease in a Dish
Identifying the culprits behind neurological disorders like Alzheimer’s, Schizophrenia, and Autism — whether they be genetic, environmental, biological, or a tricky combination of them all — remains one of the greatest obstacles of research. With disorders like these, the cause of onset, the mechanism of action, and the progression are still mostly unknown. Improving diagnoses and developing effective therapies cannot be curated until a target for each disorder is identified. Unfortunately for many neurological disorders, a definitive diagnosis cannot be made until a patient has died. Even then, studying post-mortem tissue presents multiple issues in translation to the living clinical population.
[…] the use of induced pluripotent stem cells (iPSCs) has provided science with a new way to model diseases and disorders — call it a disease in a dish.
Starting in 2006, the use of induced pluripotent stem cells (iPSCs) has provided science with a new way to model diseases and disorders — call it a disease in a dish. iPSCs can be differentiated into any type of cell, and it is not uncommon for labs to synthetically create functional neurons. Scientists can collect a sample of tissue like skin or spinal fluid from consenting patients with varying neurological disorders, induce pluripotent stem cells, and derive any type of cell to study a human cell line in vitro. These cells, whether they be neurons, cardiomyocytes, or intestinal epithelial cells, can be grafted into the brain of a lab animal for in vivo models.
Animal models, especially when it comes to neurological disorders, have issues with translation from dish to animal and animal to human. Parkinson’s, ADHD, Epilepsy, and other neurological disorders present differently in every patient, so imagine how hard it is to draw decisive conclusions about a human condition from a rodent. What did scientists cook up to potentially solve this issue with this heterogeneity? They started artificially growing mini organs, called organoids. An organoid is a synthetically grown, three-dimensional representation of an organ from human pluripotent stem cells (hPSCs). These organoids could solve many of the roadblocks researchers face when trying to obtain human brain tissue, and could provide more translatable data than animal models.
These organoids could solve many of the roadblocks researchers face when trying to obtain human brain tissue, and could provide more translatable data than animal models.
However, many scientists are still discussing the benefits and challenges of organoids. Organoid research lacks reliable data due to concerns regarding uncontrollable diversity within the organoid, reproducibility, and accurate representation. For example, a mini brain may not contain all five layers of the cortex, or a full vascular system. When studying disorders which affect either a fetal brain or an extremely mature brain, culturing an organoid of such specialized maturation may prove immensely difficult. Although this development is still faced with challenges, stem cell research in neuroscience is continuously progressing, so organoid research is sure to follow. Perhaps discovering the secrets behind synthetically growing mini organs in a dish will lead scientists to discover something about our own brains too.
DOIs: 10.1186/s12929–017–0362–8, 10.1242/dev.150292, 10.3389/fnins.2018.00056