While the original 2D cell culture methods remain indispensable for routine laboratory operations and biochemical analyses it has become increasingly clear that they do not accurately represent organ systems in the body. To fully understand a system or device one must deconstruct it and then rebuild a functioning version using only the constituent parts. To fully understand disease the corresponding healthy tissue must be well defined, this is often not the case due to lack of systems for study. Generation of three dimensional cellular structures from biobanked material could be part of the solution.
The commonly used 2D cell culture systems represent the deconstruction of an organ system and today this is a trivial pursuit in state-of-the-art laboratories. As cells and organs normally operate in three dimensions, the next phase of understanding with consequent improvements in disease management, will come from reconstruction, or 3D systems. Such systems include organoids, organ-on-chip technology, and 3D printing/ fabrication using “bio-inks”, all of which require biobanks for cell storage.
Organoids are multicellular structures that have a micro-anatomy representative of the original organ from which they were derived. They are often generated from stem-like cells capable of generating many different cell types. The organoid may be sufficiently differentiated to achieve some, but as yet not all, of the functions of the modelled organ.
Typical 3D culture substrates include imprecisely defined extractions of extracellular matrix, such as Matrigel. Based upon the reconstruction principle better organoid systems could be developed by defining the critical elements of these gels required for organoid development. Organoids are also limited in size and representativeness of the original organ by their lack of a vascular system, which can result in a hollow or necrotic core. Organ-on chip technologies can address these limitations.
The heart, lung, kidney, artery, bone, cartilage, skin, blood-brain barrier and more have been simulated by organ-on-chip microfluidic devices. The majority of the organ structure is simulated by the inorganic device itself with a thin layer of cells coated in a three dimensional arrangement. The use of microfluidics overcomes the inherent lack of vasculature present in most organoids.
Organ-on-chips are still in their infancy in terms of design and can answer very specifically defined questions, however due to their largely artificial construction they are not particularly well suited to genomic, or generalized studies on organ structure and or function, where organoids may be better suited for initial findings before refining the research question.
Efforts are also under way to generate whole organs by additive manufacturing, otherwise known as 3D printing. This technique can in theory precisely regenerate entire organs. The “bio-ink” used by these printers is critical and includes a mixture of cells and substrate. Optimizing “bio-ink” is a bottleneck for the successful implementation of this technology. In analogy to an inkjet cartridge, multiple “cell dyes” or types are needed to “print” the organ.
Organoids, organ-on-chip technology, and additive manufacturing of organs all require cells as a raw material, which must be well characterized and stored appropriately. Biobanking of these cells is a crucial component of these biotechnological applications and emergent industries.