Development of Neural Organoids from Pluripotent Stem Cells for Advancement of Neurological Regenerative & Surgical Treatment

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Williams, Sarah C.P. “Scientists Develop Brain Organoids with Complex Neural Activity.” UCLA, UCLA, 23 Aug. 2021, newsroom.ucla.edu/releases/brain-organoids-complex-neural-activity.

By Ambrose Loc Ngo, M.S.

Introduction

Neural organoids (also termed brain organoids) are a revolutionary development in the fields of developmental biology and neuroscience. They are three-dimensional, miniaturized versions of the brain that have been simplified and created from pluripotent stem cells which can differentiate into any type of cell (Romito et al., 2016, Zhu et al., 2013). In contrast to more traditional 2D cell cultures and animal models, creating neural organoids represents a major technological shift towards more physiologically relevant approaches that consider human brain development as well as pathology in an ethical manner (Lee et al, 2022). Per se, studying neural organoids can give us the opportunity to recreate numerous features of the brain structure and functioning such as network formation among neurons and synapse establishment (Li et al., 2023). Furthermore, neural organoids can also provide useful information related to numerous neurodevelopmental disorders including epilepsy, schizophrenia, and autism spectrum disorder (Kim et al., 2023). However, there are some challenges of using neural organoids that should be considered while studying them.

For example, neural organoids lack vascularization, have a short-term survival rate, and contain the inability to fully imitate intricate brain structure and functioning (Smirnova et al., 2024; Sun et al., 2022). As such, the rationale of this literature review is centered on diving deeper into the current knowledge of neural organoid research while also highlighting its key developments, applications, and future directions. Additionally, this review will also aim to provide a foundation to advancement of potential neurological regenerative discoveries, surgical transplant procedures, and effective treatment.

Figure 1. Pluripotent Stem Cell Diagram displaying its ability to differentiate into many cell types.

Background & Advancements

The historical growth of organoids has witnessed major strides from early attempts at three-dimensional cell structures imitating organogenesis in vitro (Corro et al., 2020, Simian et al., 2017). This progression relies on pluripotent stem cells (PSCs), which include embryonic stem cells (ESCs) that are harvested from early-stage embryos and induced pluripotent stem cells (iPSCs), which are derived from fully matured somatic cells (Aboul-Soud et al., 2021). An advantage of PSCs lies in its ability to transform into any type of cell (Figure 1), thus holding great potential for diverse organoid generations. Additionally, several techniques can be employed collectively to achieve production of neural organelles that can be used for various research purposes as well as clinical applications (Telias et al., 2023).

Characterization of Neural Organiods

To analyze their shape, the neural organoids can be characterized to evaluate their maturity as well as their functions. The layers inside them and how they are structured are checked to make sure that they resemble those of the brain (Li et al., 2023). Lastly, by studying synaptic activities of these systems, proper functioning neural connections can be formed in response to various stimuli (Lullo et al., 2017). As such, these vital techniques can overall help in research and treatment and therefore validate the use of neural organoids.

Neural Organoids Applications

Neural organoids come with a range of applications which are instrumental in biomedical research, surgical procedures, and therapy expansion. For instance, as disease models, neural organoids provide an opportunity to study some specific neurological disorders such as Parkinson’s, dementia, or neurodevelopmental diseases like autism and schizophrenia under controlled laboratory conditions (Wang et al., 2018). Therefore, new possibilities can arise when brain organoids are used in drug discovery and toxicity screening like finding therapeutic drugs by testing them on animal models. This can also aid in personalized medicine through patient-specific organoids that guide treatment based on genetic makeup of a patient (Li et al., 2020)

Challenges & Limitations

Development and application of neural organoids face several challenges and limitations (Figure 2). For instance, scalability and reproducibility remain technical barriers as many good quality brain-like masses cannot be generated simultaneously due to cell diversity and unique differentiation processes (Andrews et al., 2022). In addition, long-term culture stability has been an issue leading to variability and loss of function over time (Andrews et al., 2022). Furthermore, the involvement of human embryonic cells in research poses ethical problems in this area which make it more complicated especially when legal restrictions become involved (Lo et al., 2009). Therefore, meeting these challenges would determine how we navigate forward in neuroscience research and clinical practice.

Conclusions & Outlook

Future directions in the study of neural organoid models look forward to surmounting leading challenges and maximizing their capabilities to contribute to the development of regenerative medicine and surgical treatment. Thus, attempts are being made to make these organoids more complex and functional to be able to imitate the intricacies within human brain structures and functions (Bai et al., 2024). Furthermore, infusing artificial intelligence with data analytic skills can facilitate the interpretation of intricate information sets; thus, it will increase efficiency as well as accuracy in research (Bai et al., 2024). Personalized organoids also have the potential for developing personalized medicine therapy and surgical procedures for patients (Li et al., 2020).

To sum up, this literature review reflects significant progress in neural organoid research displaying how they may change our perception about human brains while developing new treatment approaches. Irrevocably, widening the application of neural organoids into other neurological diseases may foster their reach hence generating novel ideas and therapeutic possibilities with a wide range of conditions (Shou et al., 2020). Additionally, this topic is bound to bring major changes in science related to brain functioning as well as its disorders. As such, it will revolutionize patient care through its innovations which can be found in neuroscience or medical practice beyond any reasonable doubt.

 

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