Stemness refers to the unique property of certain cells to both self-renew and differentiate into various specialized cell types. This characteristic is central to how multicellular organisms develop, grow, and maintain their tissues. Understanding stemness is important for advancing biological knowledge and holds promise for medical applications.
Defining Stemness
Stemness encompasses two primary capabilities: self-renewal and potency. Self-renewal describes the ability of stem cells to divide and produce more stem cells, maintaining an undifferentiated state.
Potency refers to the capacity of stem cells to differentiate into various specialized cell types. Different levels of potency exist, indicating the range of cell types a stem cell can become. Totipotency, the highest level, means a cell can form all cell types of a complete organism, including both embryonic and extraembryonic tissues like the placenta. The zygote, a fertilized egg, and the cells from its first few divisions are examples of totipotent cells.
Pluripotency allows cells to differentiate into all cell types that make up the three germ layers of an embryo—ectoderm, mesoderm, and endoderm. Pluripotent cells cannot form extraembryonic tissues. Embryonic stem cells are an example of pluripotent cells.
Multipotency describes a more restricted potential, where cells can differentiate into a limited number of cell types within a specific lineage or tissue. Hematopoietic stem cells in bone marrow, for instance, are multipotent as they can produce all types of blood cells. Unipotency is the most limited form of potency, where a cell can only differentiate into one specific cell type, such as basal cells in the epidermis that produce more skin cells.
Sources of Stem Cells Exhibiting Stemness
Cells exhibiting stemness are found in several distinct biological sources. Embryonic stem cells (ESCs) are derived from the inner cell mass of a blastocyst, which is an early-stage embryo typically 4-7 days after fertilization. These cells are pluripotent, meaning they can develop into any cell type of the body but not the placenta or other extraembryonic tissues.
Adult stem cells, also known as somatic stem cells, are present in various tissues throughout the body, including bone marrow, skin, brain, and blood vessels. These cells are multipotent or unipotent, and their primary role involves maintaining and repairing the specific tissues in which they reside. While they can self-renew, their capacity to divide is limited.
Induced pluripotent stem cells (iPSCs) are generated in a laboratory setting by genetically reprogramming adult somatic cells, such as skin or blood cells, to revert to a pluripotent state. This process involves introducing specific genes into the somatic cells. iPSCs are similar to embryonic stem cells in their ability to self-renew and differentiate, offering a patient-specific source of pluripotent cells without the ethical concerns associated with embryonic sources.
Cancer stem cells represent a distinct subpopulation within tumors that exhibit properties of stemness. These cells are thought to contribute to tumor initiation, growth, metastasis, and resistance to conventional cancer therapies. Their persistence within tumors is hypothesized to lead to disease recurrence.
Biological Roles of Stemness
Stemness plays an important role in the natural processes of living organisms, particularly in development, tissue maintenance, and repair. During embryonic development, stemness drives the process by which a single fertilized egg gives rise to all the diverse tissues and organs of a complex multicellular organism. Embryonic stem cells, with their pluripotent capacity, differentiate into the three primary germ layers—ectoderm, mesoderm, and endoderm—which then form every cell type in the adult body.
Throughout an organism’s life, adult stem cells continuously contribute to tissue maintenance and homeostasis. These cells reside in specific “niches” within various tissues, acting as an internal repair system. For instance, hematopoietic stem cells in the bone marrow constantly replenish all types of blood cells, while skin stem cells facilitate the continuous renewal of the epidermis. This ongoing replacement of worn-out or damaged cells is essential for maintaining the structure and function of organs like the gut lining and liver, which undergo frequent cell turnover.
Stem cells are also important in the body’s ability to repair and regenerate damaged tissues following injury. When tissue damage occurs, quiescent adult stem cells are activated, proliferating and differentiating to replace lost cells and restore tissue function. This regenerative capacity is evident in processes like wound healing, where dermal stem cells contribute to skin repair. Stem cells are responsible for healing bone fractures and repairing cardiac tissue.
Applications of Stemness in Medicine
The unique properties of stemness have opened new possibilities in medical science, particularly in regenerative medicine and cell therapies. Stem cells are utilized to repair or replace tissues and organs damaged by disease, injury, or aging. A well-established example is bone marrow transplantation, where hematopoietic stem cells are used to treat blood cancers like leukemia and certain blood disorders by replacing diseased blood cells with healthy ones. There is also research into using stem cells to treat spinal cord injuries, heart disease, and neurodegenerative disorders. Mesenchymal stem cells are being investigated for their potential in regenerating cartilage in osteoarthritis and other musculoskeletal conditions.
Stem cells are also valuable tools for disease modeling, allowing researchers to study the mechanisms of human diseases. By deriving induced pluripotent stem cells (iPSCs) from patients with specific genetic conditions, scientists can create patient-specific models of diseases. This allows for a deeper understanding of how these conditions develop and progress at a cellular level, overcoming limitations of animal models.
Stem cell-derived tissues are employed in drug discovery and testing. These models provide a human-relevant platform to screen potential drug compounds for their efficacy and toxicity early in the development process. For example, iPSC-derived heart cells can be used to assess the cardiac safety of new drugs before clinical trials, potentially reducing the time and cost associated with drug development and minimizing risks to patients.