The biology of self-sustaining systems
Ouroboros is a popular symbol representing the eternal cycle of continuous renewal and death, traditionally depicted as a serpent consuming its own tail. Its origins lie in mythology and religion, but stem cells present an accurate parallel to this ancient metaphor, embodying the principle of self-renewal at the biological level.
First mentioned in 1868 by Ernst Haeckel, the stem cell was used to describe the unicellular ancestor, and the fertilized egg was thought to give rise to all multicellular organisms and the cells within. Today, stem cells are now defined by two significant properties: self-renewal, the ability to divide and produce identical copies of themselves, and differentiation, the ability to become specific types of cells.
These defining properties form the foundation of human development, tissue maintenance, and regeneration. A key mechanism supporting this self-renewal is asymmetrical division, in which a daughter cell retains the stem cell identity while the other differentiates into a specific cell type. This process allows tissues to replace damaged cells while preserving a steady population of stem cells.
Stem cells can also be categorised according to their origin and potential for differentiation. Embryonic stem cells come from the embryo and are pluripotent, meaning they can differentiate into nearly any cell within a human. In contrast, adult stem cells are typically found in specific tissues, such as bone marrow, and are multipotent, since each type of adult stem cell can only produce specific cells of its tissue of origin.
The limitations of the adult stem cell differentiation have been counteracted by Shinya Yamanaka, who led the discovery of induced pluripotent stem cells (iPSCs). These stem cells are adult cells which can be reverted to a pluripotent state, allowing them to differentiate into a wide variety of cell types. This is one of the most significant findings as it allowed researchers to improve modelling of human diseases, drug efficacy, and cell-based therapies. However, ensuring that iPSCs remain genetically stable during reprogramming and reliably differentiate into the appropriate cell types present safety challenges for their clinical application.
Despite these challenges, stem cell based therapies have already made a significant clinical impact. The most established example is bone marrow transplantation of hematopoietic stem cells, which is used to treat patients with cancers and disorders affecting the blood and immune system. In addition, stem cells have been successfully utilised for skin grafts for severe burns, demonstrating their capacity to restore damaged tissues. Clinical trials are also being held for numerous other disorders and diseases such as Alzheimer’s, Parkinson’s, depression, diabetes, and macular degeneration, to name a few.
Unfortunately, the development and approval of these therapies are slowed by the challenges researchers face with immunorejection, specific differentiation, and stem cell functions in an injured microenvironment. Yet, the ongoing advances in stem cell biology provide a promising future in understanding these complex biological systems. As researchers better control the balance between renewal, differentiation, and application, the Ouroboros may no longer be confined to just an ancient symbol.