Author: Chandan Seth Edited by: Inês Barreiros
Reproduction, a fundamental feature of biology, inevitably defines our existence and that of the world around us. Although half a century ago it was much believed that life around us was initially generated from a primordial soup of RNA, this concept of an ‘RNA world’ was dismissed based on the central dogma of molecular biology, which explained the unidirectional flow of information from DNA to RNA and therefore to proteins. Shortly after, it became apparent that life on Earth was initiated with Archaea, the single-celled organisms, which divided and proliferated to establish a dynamic exchange of material and energy and created ‘life cycles’. Soon after, the concept of ‘Omnis cellula e cellula’, that is, all cells come from cells, established the basic principle of procreation. Since then, this concept, as proposed by Rudolf Virchow, has been the functional principle and definition of cellular biology. Today, what we know as ‘the concept of stem cells’ is an extended definition of Rudolf Virchow’s principle in multicellular organisms.
During development and tissue homeostasis, a synchrony of signals defines the state of cells and their fate. However, stem cells can be classified as specialised cells that own the capacity to indefinitely renew, regenerate and proliferate, but under distinct conditions. As it stands, the concept of stem cells establishes the prophecy of these cells as governors of tissue homeostasis, morphogenesis, degeneration and invasion. To fortify this paradigm, several model systems have been employed under the state of normal development and in diseases like cancer.
To understand the role of stem cells as the governors of cellular fate in cancer, many model systems, encompassing tissues of various origins in human/murine system, have been employed. These stem cell counterparts in abnormal tissue development in case of cancer have been termed as ‘cancer stem cells’. More recently, many studies have implicated the role of these cancer stem cells in tumour initiation, progression, invasion and drug resistance. To this end, these cells have been proposed as therapeutic targets and have taken the centre-stage of anti-cancer therapy.
Given the complexity of biological networks in living organisms, scientists often resort to much simpler models with similar characteristics to establish the basic principles of life. In the last few decades, they have succeeded in establishing two- or three- dimensional cellular models in the laboratory, derived from healthy and diseased individuals, or even experimental mice. These models have played a vital role in understanding disease and accelerating anti-disease drug development and become an obvious and relatively relevant choice for drug testing and pharmacology.
As is clear from the terminology, each ‘model’ is hence a three-dimensional representation of the biological system and does not mimic the system in entirety. Therefore, scientists keep devising the ameliorated versions of these models to mimic the living system. Of note, a recent model to understand the role of stem cells in health and disease is that of the ‘organoid’ culture. Organoids are miniature organ-like tissues artificially grown from a single cell on a plastic dish, in a scientific laboratory. This model is based on the simple principle that stem cells harbour self-organisation, regenerative potential and can mimic tissue architecture and growth in a rather representational manner. Very recent attempts to recreate parts of intestine, stomach, esophagus, liver and heart tissues have been successful in scientific laboratories, and the so-developed ‘organoids’ for each of these systems are now being used as models for understanding further biology and drug action.
Though it is an incredible feat for scientists around the world, this model system too, like others, is far from being vivid, since biological systems comprise of multiple cell types and signals. The lack of context or micro-environmental influences on these solitary stem cells, places these single-cell models in questioning.
Apart from these models, there are several approaches to address the mysteries of biological systems. Inter-disciplinary approaches such as intertwined mathematical, chemical and physical sciences have developed model systems to simulate cellular biology and dynamics of biological reactions. As it stands, the past century has witnessed unprecedented success in scientific achievements to mimic life and yielded an incredible amount of knowledge. Yet, it is becoming seemingly clear that these models are not an end, but a means to the end, and there are miles to go before we sleep.