The field of stem cell research has been expanding at a rapid pace, and it holds enormous potential for the medical community. All living things are composed of cells, which can either remain undifferentiated as stem cells and continue dividing to produce more of the same or differentiate into more specialized cell types, such as nerve, heart muscle, or blood cells. Specialized cell kinds are grown from these cultured cells so that they can be studied for research into diseases and potential treatments or medications. As a result, they are also being employed to replace and repair cells that have been damaged or weakened by disease. Brain organoids, which may simulate the behavior of the entire human brain or just certain regions, are one type of specialized cell that is being produced and studied in great detail.
What Are Brain Organoids?
A brain organoid is an artificially grown organ resembling the brain to examine its intricate function and structure. Studying a specific brain function or neurological condition can be challenging due to the brain’s many simultaneous functions. Thus, researchers cultivate brain cells in a petri dish to examine a specific brain function or neurodegenerative disease, with the hope of one day discovering a treatment.
How Are Brain Organoids Grown?
Pluripotent stem cells, which have the potential to differentiate into various other cell types, are used to cultivate brain organoids. Typically, they undergo a transition into one of the three germ layers (mesoderm, endoderm, or ectoderm). Induced pluripotent stem cells are pluripotent stem cells that can be created directly from somatic cells, the basic unit of all multicellular creatures. These human induced pluripotent stem cells (iPSCs) have the ability to develop into any cell or tissue type present in the human body given the right environment. This technology was mastered by Shinya Yamanaka and Sir John Gurdon, who were awarded the Nobel Prize 2012 in Physiology or Medicine for this achievement. After that, the same method was applied to the creation of brain organoids. Cultured human pluripotent stem cells are developed into embryoid bodies with three distinct germ layers. These embryoid bodies are induced to form neuroectoderm derived from the ectoderm germ layer. They are then placed in a nutrient-rich medium such as Matrigel, an extracellular matrix utilized in cell culture by scientists. To encourage tissue growth and neuronal development, this setup is cultivated in rotating bioreactors. With no external interference, these cells self-organize by themselves into a heterogenous brain organoid that can resemble many brain regions. It is through this process, known as unguided differentiation, that brain organoids are created. However, for guided differentiation, extracellular cues are introduced to the environment at various stages of development so that brain organoids take on the appearance of a specific brain region. iPSCs are given specific instructions, in the form of small chemicals and growth factors, to differentiate into cells and tissues that resemble specific parts of the brain, such as the cerebral cortex, hippocampus, and midbrain. As the great unpredictability and heterogeneity of the unguided method provide substantial hurdles for further studies, this technique is typically utilized for producing organoids.
How Are Brain Organoids Used?
Brain organoids are primarily being used to study several neurological and neurodegenerative disorders like Alzheimer’s, Parkinson’s Disease, and glioblastomas, to name a few. The scientific and medical communities still don’t know what causes many of these ailments. Therefore these organoids can be utilized to learn more about the underlying causes and test new treatments and medications. Moreover, they bridge the gap between research conducted on animals and that conducted on human patients. Due to their significant differences from human brains, animal brains were proving to be inadequate in the investigation of these illnesses. Neurodevelopmental diseases are also being studied by cultivating organoids to examine their onset in the fetal or embryonic phases of development. In addition, they can be used to regrow a damaged area of the brain for transplantation as a therapeutic measure. Dedicated researchers at top universities have created organoids to investigate the root causes of several different diseases. Some researchers in the field of neuroscience have even employed their utilization in order to investigate the brain’s features and dynamics.
Future of Brain Organoids
Even though there have been several breakthroughs in the field of brain organoids in the past decade, this technology is still in its infancy. Because organoids developed today lack a circulatory system, they obtain their oxygen and nutrients by diffusion from the culture medium. Due to a lack of oxygen and nutrition, portions of the organoid’s cells may die over time. Consequently, it is essential to develop methods of cultivating organoids with an enhanced blood circulation system, allowing them to survive for several years. In order to study organoids for longer periods of time, many researchers have been working on creating models with closed-circulation systems. Another option being investigated is to transplant the mature organoid into the brain of a mouse, where it can continue to grow and be researched in depth.
Furthermore, there is a lot of variation and not a lot of reproducibility in the existing approach of generating brain organoids. This means that even among batches of the same type of organoids generated in the same facility, there might be significant variation. As a result, there may be no benchmarks or established procedures against which the findings can be evaluated. Some types of neurons found in the human brain are absent in these organoids as well. Growing a fully functional, state-of-the-art organoid from stem cells is still a ways off, but the field is making remarkable strides for it to happen.
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