For decades, the concept of a stem cell that could be generated from a non-embryonic source had been a mere scientific fantasy. In 2006, Shinya Yamanaka realized this major breakthrough in stem cell technology by discovering a way to reprogram adult somatic cells, mature cells, found everywhere in the human body such as skin or blood, into pluripotent embryonic stem cells (1). His discovery not only won the 2012 Nobel Prize in Physiology or Medicine, but became the beginning of an unprecedented scientific and medical revolution. Miniature organs could model diseases right before one’s very own eyes, and medical treatments that could regenerate damaged tissue from scratch (2).
The decades-long story of stem cells began in the late 19th century imperial Germany, where Ernst Haeckel coined the term stem cell as “Stammzelle” or “stem cell” to describe the fertilized egg that gives rise to all cells in the body3. In the early 1900s, Theodor Boveri, another scientist studying embryos, further emphasized the dual ability of stem cells for both self-renewal and differentiation (3). In 1981, scientists developed techniques to isolate embryonic stem cells from early mouse embryos, leading to another major breakthrough in 1998: the discovery of a method to extract stem cells from human embryos and cultivate them in laboratory settings (4).
Stem cells possess two crucial features that characterize them as such. First, they have the ability to replicate themselves in a process of self-renewal (5). Under the correct chemical conditions, they can also undergo differentiation, transforming into various specialized cell types with distinct functions (5), such as a pacemaker cell found in the heart or a hippocampal neuron found deep within the brain.
In the mature human body, there exist many types of stem cells found in various locations. Each is involved with the renewal of specific tissue types and repairing damages caused to that tissue (5). Although these cells have such regenerative capabilities, they are very limited in the types of cells they can generate and may only contribute to the maintenance and repair of their tissue of origin (5).
Looking earlier into human development, one would find stem cells with a greater ability to differentiate into a greater variety of cell types: the embryonic stem cell, present in the earliest stage of development (4). Embryonic stem cells (ESCs) are pluripotent, meaning they have the ability to develop into all types of somatic cells found in a human6. It has been long recognized that they have the potential to serve as extremely accurate experimental models for embryonic development and differentiation, as well as disease models (6). Most extraordinarily, stem cells hold significant therapeutic potential, specifically in generating specialized cells to replace damaged tissues in individuals afflicted with degenerative diseases such as Parkinson’s or amyotrophic lateral sclerosis (6).
While the promise of tissue regeneration sounds ideal, human embryonic stem cells come with many ethical issues. Human embryonic stem cells were and still remain controversial due to their reliance on the destruction of human embryos (7). In the United States, human embryonic stem cell research has also been often intertwined with debates surrounding abortion (7).
With Yamanaka’s breakthrough discovery in 2006, induced pluripotent stem cells avoid this issue entirely. From a mere 1-5 milliliters of blood or some skin tissue samples, completely mature epithelial or connective tissue can be reprogrammed into its embryonic state and can generate an unlimited number of cell types of choice from any of the three germ layers (2,8).
To create an iPSC, one must ectopically introduce and make the desired cells express four transcription factors: OCT4, SOX2, KLF4 or MYC, and NANOG or LIN28 collectively referred to as OSKM8. These factors will activate the expression of genes associated with pluripotency, which will turn somatic cells back into a state resembling embryonic stem cells.
Induced pluripotent stem cells have an unlimited range of exciting applications. From forming mini, out-of-body (in vitro) organs called “organoids” to the creation of patient-specific treatments for healing once deemed incurable conditions, iPSCs have sparked a revolution in biomedical research (10). Their versatility promises to propel ongoing advancements, reshaping the landscape of medical science as we know it.