Building Complex Life Through Self-Organization

Abstract

Cells are inherently conferred with the ability to self-organize into the tissues and organs comprising the human body. Self-organization can be recapitulated in vitro and recent advances in the organoid field are just one example of how we can generate small functioning elements of organs. Tissue engineers can benefit from the power of self-organization and should consider how they can harness and enhance the process with their constructs. For example, aggregates of stem cells and tissue-specific cells benefit from the input of carefully selected biomolecules to guide their differentiation toward a mature phenotype. This can be further enhanced by the use of technologies to provide a physiological microenvironment for self-organization, enhance the size of the constructs, and enable the long-term culture of self-organized structures. Of importance, conducting self-organization should be limited to fine-tuning and should avoid over-engineering that could counteract the power of inherent cellular self-organization. Impact Statement Self-organization is a powerful innate feature of cells that can be fine-tuned but not over-engineered to create new tissues and organs.

Keywords: 3-D cell culture; organoids; self-organization.

FIG. 1.

Self-assembly can induce the formation of the skin epithelium, self-patterning forms the pancreatic islets of Langerhans, and self-driven morphogenesis induces self-organization of a neuron. It becomes more difficult to induce self-organization as tissues become more complex, for example, with more cell types or less differentiation potential. Tissue engineers can fine-tune self-organization with their technologies like microfluidics and microfabrication that can provide small molecules and an engineered microenvironment to enhance the size, long-term culture, perfusion, maturity, and complexity of the self-organizing structures, without over-engineering by interfering with the process of self-organization itself.