Stem cells are cells characterised by two important properties, the ability to self renew and the ability to differentiate into one or more specialised cell types. Self renewal means that stem cells can undergo cell division while maintaining a population of cells with stem cell characteristics. Differentiation means that descendants can acquire specialised structures and functions, such as becoming nerve cells, muscle cells, blood cells or epithelial cells. Stem cells exist in different forms and their developmental potential varies.
Pluripotent stem cells can give rise to cell types derived from the three primary embryonic germ layers, while multipotent stem cells can produce a more restricted range of related cell types. Stem cells are therefore defined by developmental potential and self renewal rather than simply by being immature or rapidly dividing cells.
Embryonic stem cells are pluripotent cells derived from the inner cell mass of the early mammalian blastocyst. They can proliferate extensively under appropriate laboratory conditions while retaining the capacity to differentiate into many specialised cell types. Adult or tissue stem cells are found in developed tissues and generally have more restricted potential. Haematopoietic stem cells in bone marrow, for example, can generate the major blood cell lineages. Intestinal stem cells contribute to continual renewal of the intestinal epithelium. Neural stem cells can generate particular neural cell types under appropriate conditions, although their capacity and significance in adult tissues depend strongly on biological context. These different stem cell populations are adapted to the maintenance and repair requirements of particular tissues.
Induced pluripotent stem cells are generated when specialised adult cells are experimentally reprogrammed into a pluripotent state. Researchers discovered that introducing particular transcription factors can reset aspects of cellular identity and produce cells resembling embryonic stem cells in their developmental potential. This discovery demonstrated that differentiated cell identity is not necessarily permanently fixed and opened major research possibilities.
Induced pluripotent stem cells can be generated from an individual's own cells, allowing researchers to study genetic diseases in laboratory models and potentially develop patient specific cell based approaches. They also avoid some of the ethical issues historically associated with obtaining embryonic stem cells, although they introduce their own technical challenges, including genomic changes, incomplete reprogramming and potential tumour formation.
Stem cell potency describes the range of cell types into which a stem cell can differentiate. Totipotent cells have the broadest developmental potential and can give rise to the embryonic and extraembryonic components required for development of a complete organism under appropriate conditions. Pluripotent cells can produce cell types from the three embryonic germ layers but generally cannot independently produce all extraembryonic structures required for complete development.
Multipotent cells can generate several related cell types within a particular tissue or lineage. Oligopotent cells have a narrower potential, while unipotent cells produce a single principal differentiated cell type but may retain self renewal. These terms describe a continuum of developmental potential rather than a simple distinction between stem and nonstem cells.
Stem cells are maintained partly through specialised microenvironments called niches. A niche consists of surrounding cells, extracellular matrix, signalling molecules, nutrients and physical conditions that influence stem cell behaviour. Signals from the niche can regulate whether stem cells remain quiescent, self renew, divide symmetrically or asymmetrically, or begin differentiation. Stem cell divisions can therefore produce two stem cells, two differentiating descendants or one stem cell and one differentiating cell depending on context. This balance allows tissues to maintain a sufficient stem cell population while continually producing specialised cells. Disruption of stem cell regulation can contribute to tissue degeneration, abnormal growth or cancer, demonstrating the importance of tightly controlled self renewal and differentiation.
Stem cells have major roles in normal tissue maintenance. Many tissues continually lose cells through ordinary wear, damage or programmed cell death and therefore require replacement. Blood cells, skin cells and intestinal epithelial cells are examples of populations that undergo substantial turnover. Tissue stem cells provide a renewable source of descendants that mature into functional cells. In some tissues, stem cells remain relatively inactive until injury or physiological demand increases the need for regeneration. The capacity for regeneration varies greatly among tissues. Some tissues can regenerate extensively, while others have limited regenerative capacity because their stem cell populations are restricted or because mature cells have limited ability to divide.
Stem cell research has applications in developmental biology, disease modelling, drug testing, regenerative medicine and transplantation. Haematopoietic stem cell transplantation is an established medical treatment for several blood disorders and cancers. Researchers are investigating stem cell derived cells for conditions involving damaged neurons, heart muscle, pancreatic cells, retinal cells and other tissues. Laboratory stem cells can also be used to model disease processes and test potential medicines. However, successful clinical use requires careful control of differentiation, cell purity, immune compatibility, genetic stability and tumour risk. Producing a desired specialised cell type is only one stage of therapy. The cells must also survive, integrate appropriately, function correctly and avoid producing unwanted tissues.
Stem cells should not be equated with cells that can automatically regenerate any tissue. Their potential is biologically constrained by genetic regulation, epigenetic state, signalling environment and developmental history. Differentiation involves changes in gene expression that establish specialised cellular programmes. Transcription factors, chromatin modifications, signalling pathways and interactions with neighbouring cells all influence these decisions. Stem cells are therefore powerful biological systems but not unrestricted biological building blocks.
Their study has transformed understanding of development and regeneration while also revealing the complexity of cellular identity. Current stem cell biology combines molecular genetics, developmental biology, tissue engineering, bioengineering and medicine to understand how controlled self renewal and differentiation can be used safely and effectively.
