Assembloids are engineered models that bring together different types of human tissues or organoids, which are miniature, self-organizing versions of organs grown in a laboratory. This three-dimensional platform allows scientists to explore complex biological systems, particularly those involving intricate interactions between multiple tissues, in a controlled environment. They offer a breakthrough in understanding how various parts of the body communicate and function together, providing insights previously difficult to obtain.
Understanding Assembloids
Assembloids are distinct from simpler organoids because they integrate multiple, differentiated cellular components. While organoids typically derive from a single type of stem cell and mimic a specific organ, assembloids combine two or more organoids, spheroids, or cultured cell types. This multi-tissue nature allows them to replicate an organ’s structural and functional properties more comprehensively by modeling inter-cellular and inter-regional interactions. Their creation stems from the need to investigate biological processes and diseases that involve communication and interplay between different bodily systems, which single-tissue models cannot fully capture.
For instance, assembloids can be designed to study the brain by combining dorsal and ventral forebrain organoids to observe how cortical interneurons migrate and integrate into neural circuits. Other combinations include thalamic and cortical neural organoids to model thalamo-cortical projections, or cortico-striatal assembloids to generate initial motor planning circuits. Beyond the nervous system, researchers can combine gut and nerve tissues to investigate the gut-brain axis, or liver and pancreas components to study metabolic interactions. These complex structures offer a more physiologically relevant system for research.
Building Assembloids
The process of creating assembloids begins with induced pluripotent stem cells (iPSCs), specialized cells capable of differentiating into various cell types. These iPSCs are first directed to differentiate into specific cell types or individual organoids, such as brain or gut organoids, by providing appropriate growth factors and signaling molecules. This initial differentiation step ensures that the precursor components are well-formed and specialized.
Following the formation of individual organoids, the “assembly” phase involves bringing these distinct components together to encourage their integration and communication. Techniques such as co-culture methods, where different organoids are placed in close proximity, allow them to self-organize and fuse. Microfluidic platforms can guide the assembly and facilitate nutrient and waste exchange, while 3D bioprinting offers a method for spatially arranging different cell types and organoids with precision. A challenge lies in coaxing these disparate tissue types to connect and function cohesively, requiring innovative approaches to guide their self-organization and ensure functional connections.
Research Insights from Assembloids
Assembloids open new avenues for scientific research, enabling the study of complex biological phenomena. In neurological diseases, for example, assembloids model how different brain regions interact in conditions like Alzheimer’s or Parkinson’s disease. By fusing organoids representing distinct brain areas, scientists observe aberrant neuronal connectivity or protein aggregation that contributes to disease progression. This allows for a deeper understanding of the mechanisms underlying these complex disorders.
Assembloids are also utilized to investigate the gut-brain axis, a bidirectional communication system between the gastrointestinal tract and the central nervous system. By combining gut organoids with neural components, researchers study how microbial products or inflammatory signals from the gut influence brain function and contribute to neurological or psychiatric conditions. These models are also valuable in developmental biology, providing insights into how different parts of an embryo interact during formation. They show how various cell lineages migrate and integrate to form functional tissues and organs. Assembloids also offer a platform for studying the multi-organ effects of drugs or toxins, allowing for comprehensive toxicity screening and drug discovery efforts.
The Impact of Assembloids on Scientific Discovery
Assembloids impact scientific understanding by bridging the gap between traditional two-dimensional cell cultures and complex animal models. They offer a more physiologically relevant system for research, providing a human-specific context that animal models may not fully replicate. This relevance is important for studying human-specific diseases and drug responses.
Their contribution to understanding inter-tissue communication is substantial, allowing scientists to observe how different organ systems interact and influence each other’s function. This capability uncovers disease mechanisms involving multiple organ systems, leading to a more holistic view of pathology. Assembloids also improve drug discovery and toxicity testing by providing accurate human-specific models, potentially reducing reliance on animal testing and accelerating new therapies. They accelerate discovery and pave the way for novel therapeutic strategies and personalized medicine approaches, advancing human health.