Many diseases affect the human body, particularly the human brain. Some of these brain diseases are especially hard to understand, diagnose, and treat, Alzheimer’s, Parkinson’s, Huntington’s, and different brain tumors to name a few. Then enters cerebral, or neural organoids. Cerebral organoids are “human-induced pluripotent stem-cell” (Logan et al., 2020) derived three-dimensional organized tissues grown in vivo in cultures that resemble brain-like areas in a developing human brain. These cerebral organoids can be the key to helping scientists and doctors learn the mechanisms of different diseases, as well as different ways to treat these major brain diseases.
In the paper, “Dynamic Characterization of Structural, Molecular and Electrophysiological Phenotypes of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids, and Comparison with Fetal and Adult Gene Profiles”, Thiago Azura and colleagues show how cerebral organoids function and display various features that are seen in the human brain. In the paper, they found that cerebral organoids display electrophysiological properties and electrical activity as seen in human brains. They also display heterogeneous gene and protein expression for different neural type markers, smooth muscle cells, endothelial cells, and synapses (which display neurotransmitter vesicles and post-synaptic neurotransmitter communication). They also found channel currents, such as NMDA, glutamate, and other receptors, and found gene profiles closely related to signaling pathways and electrophysiological pathways in the brain. These features could be the key to using cerebral organoids as brain models to help understand and combat diseases. With further bioengineering of cerebral organoids, even more features could be found in these organoids so that they are our closest biological model to the real human brain (without using the brain itself). Cerebral organoids were found to be closely related to the brain of fetuses, though, not adult human brains, which pose an issue in using them to understand diseases that affect adults. However, with the ever-evolving biotechnological field, cerebral organoids may soon be able to resemble adult brains and have almost all of the features of a human brain. These organoids could then be used to treat difficult brain diseases, such as glioblastomas.
In the article, “Brain tumor organoids may be key to time-sensitive treatments for glioblastomas”, from the University of Pennsylvania School of Medicine, doctors and scientists look to treat glioblastoma multiforme, one of the common and more aggressive brain cancers, which are often very difficult to treat (treatments now only slow the rate of tumor growth but does not completely remove the tumor and cancer from the brain). The lab at UPenn School of Medicine used the mapping of cerebral organoids and formed brain tumor cerebral organoids in vivo from the glioblastoma cells and tissues of glioblastoma patients, with the hopes of understanding the key features of individual patient’s diseases. These organoids can be grown to resemble the genetic composition, cell heterogeneity, and structure of glioblastomas in patients, which could then be used to understand them better and find better ways to treat the disease. The organoids are promising because they do not take long to grow in the lab, which helps with cancer treatment progressing faster. In the most recent study in the lab, they found that they grew glioblastoma organoids at a 91.4 percent success rate within two weeks. They also found that the organoids retain most of the features from the original tumors. When transplanted into the mouse brain, the glioblastoma organoids functioned as they would in human brains, invading the brain tissue surrounding the rapid infiltrating cancer cells. They also found promises in CAR T therapies by testing them on the mouse subjects. These results all highlight the hope that glioblastoma organoids can be used to create effective personalized treatments for glioblastoma patients.
Cerebral organoids at the moment, as shown by Azura et. al, closely relate and resemble the fetal human brain, and in the future could soon be resembling adult brains. Azura and colleagues also display that cerebral organoids show key features found in the human brain, such as electrical activity and certain gene profiles, and these features give hope that with further development, cerebral organoids could soon be used to understand debilitating brain diseases. Future more-developed cerebral organoids could also help to develop effective treatments for these diseases through clinical trials and further experiments. Even now, cerebral organoids are showing promise in treating brain cancers, as shown through the experiments done by the University of Pennsylvania School of Medicine, where they are developing and growing cerebral organoids to understand glioblastomas. With the increasing evolution of biotechnology and increasing knowledge found to develop these mini-brains, cerebral organoids could be used as models to understand and treat any type of difficult brain disease in the future.
References
Logan, Sarah, et al. “Dynamic Characterization of Structural, Molecular, and Electrophysiological Phenotypes of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids, and Comparison with Fetal and Adult Gene Profiles.” Cells, vol. 9, no. 5, 2020, p. 1301., doi:10.3390/cells9051301.
University of Pennsylvania School of Medicine. “Brain Tumor Organoids May Be Key to Time-Sensitive Treatments for Glioblastomas.” ScienceDaily, ScienceDaily, 26 Dec. 2019, www.sciencedaily.com/releases/2019/12/191226151741.htm.
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