Biomedical Boon: Lab-cultured Cerebral Tissue

Written by Ashima Seth and Edited by Gouri Ajith

Brain Organoid. Vaccarino Lab, Yale University.

Humans, for as long as we have been thinking about our place in the animal kingdom, have been asking the question: what makes us so different from other animals? The answer, according to biochemical, biophysical and socio-behavioural scientists, and as many now know, is our highly developed brain. Scientific advancements in the last few decades alone have helped further our understanding of the brain’s workings and related medical conditions by leaps and bounds. However, due to several ethical concerns regarding experimentation on humans, research as to the actual development of the brain and testing of drugs has been limited to the brains of mammals with lower cognitive functioning, like that of mice [1]. Now, advancements in laboratory techniques are allowing for the growth of cerebral organoids, or mini-human brains, artificially in vitro (that is, in a lab environment versus inside a body). This advancement has the potential to break the barrier placed on research by providing access to human brains.

The biological precedent that allows for this growth of brain tissue under laboratory conditions is the manipulation of human pluripotent stem cells (PSCs), which are cells obtained from human embryonic or fetal tissue that have the potential to develop into many different cell types of the body (for example, brain or muscle cells). Organoids are, at present, smaller and less complex models of organs, such as the brain, that are grown via a 3-D tissue culture of human PSCs [2]. Since the first documented use of this lab technique to grow cerebral organoids in 2013 by Lancaster and his lab, the procedure has been refined considerably. Recent advancements have allowed for PSCs to develop into different cell subtypes and into a complex yet delicate cell organization and association pattern that closely mimics fetal brain development patterns in humans [3]. Furthering this breakthrough, a recent study by Case Western Reserve University has achieved advanced development of oligodentrocytes in cerebral organoids; an oligodentrocyte is a specific type of brain cell that supports and insulates the fibers of the brain (nerve fibers), which are used as communication pathways between different brain cells. Oligodentrocytes create a material called myelin sheath, which is composed of layers of fat, to wrap around nerve fibers for their protection and to increase the speed of communication between cells. This highly complex level of oligodentrocyte development was not present in preceding models [4].

Organoid lab-culture is proving to be an amazing source for furthering our knowledge on the development of the human brain, and tracing developmental abnormalities to structural anomalies. In addition, organoids provide an advanced testing ground for drugs – allowing for first-hand observation of the effect of a drug on the human brain tissue. For example, in the study conducted by Case Western Reserve University, the PSCs of patients with Pelizaeus-Merzbacher disease (a birth defect involving oligodendrocyte development without myelin sheath formation around nerve fibers), were used to grow organoids. These organoids were then used to test the effectiveness of drugs currently on the market that claim to treat the disorder. An increase in the amount of myelin sheath around nerve fibers was directly observed for some of these drugs [4]. The technique of growing organoids, though helpful, is still being perfected. Cerebral organoids face the limitation of being unable to sustain modeling the growing complexity of brain development in its later stages, such that only the very earliest stages of brain development are presently observable through this method. Yet another issue is that organoid samples have a high degree of variation regarding the finer details of the development and structure of individual organoids [5].

Lastly, as the scientific community moves forward with refining and expanding the growth of both the cerebral organoids and the field itself, it is important to keep in mind that such advancements in research are sparking ethical and metaphysical debates (a branch of philosophy dealing with questions of existence and being, among others), questioning if, with further advancements, these organoids could eventually develop consciousness [6].

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