What is a Cell?
A cell is the basic building block of living things. All cells can be sorted into one of two groups: eukaryotes and prokaryotes. A eukaryote has a nucleus and membrane-bound organelles, while a prokaryote does not. Plants and animals are made of numerous eukaryotic cells, while many microbes, such as bacteria, consist of single cells. An adult human body is estimated to contain between 10 and 100 trillion cells. (Source: National Human Genome Research Institute)
What is a Stem Cell?
A stem cell is a cell with the potential to form many of the different cell types found in the body. When stem cells divide, they can form more stem cells or other cells that perform specialized functions. Embryonic stem cells have the potential to form a complete individual, whereas adult stem cells can only form certain types of specialized cells. Stem cells continue to divide as long as the individual remains alive. (Source: National Human Genome Research Institute)
Why are scientists studying stem cells?
If someone were badly burned or had a genetic blood disease, imagine if scientists could repair the damaged skin or blood with new cells. This is the promise of stem cells! Scientists around the world are studying stem cells to learn how they work and how they might be used to repair bodies and cure disease. (Source: American Museum of Natural History)
Have you heard of "Pluripotent" before?
Pluripotent means many “potentials”. In other words, these cells have the potential of taking on many forms in the body, including all of the more than 200 different cell types. Embryonic stem cells are pluripotent, as are induced pluripotent stem (iPS) cells that are reprogrammed from adult tissues. When scientists talk about pluripotent stem cells, they mostly mean either embryonic or iPS cells. (Source: California Institute of Regenerative Medicine)
(Photo source: Cusabio)
What is an iPS Cell?
An induced pluripotent stem cell, or iPS cell, is a cell taken from any tissue (usually skin or blood) from a child or adult and is genetically modified to behave like an embryonic stem cell. As the name implies, these cells are pluripotent, which means that they have the ability to form all adult cell types. (Source: California Institute of Regenerative Medicine)
iPS cells were first generated by Professor Shinya Yamanaka’s group at Kyoto University. The process of changing a cell from a differentiated to a pluripotent state is called reprogramming. The method developed by the Yamanaka group has been shown to be highly reproducible, relatively simple, and is considered a major scientific breakthrough. (Source: Center for iPS Cell Research and Application, Kyoto University)
How did Professor Shinya Yamanaka’s group first generate iPS cells?
Professor Shinya Yamanaka was investigating the genes expressed in embryonic stem (ES) cells and in 2000 began searching for an alternative source of pluripotent stem cells. His group found that by introducing just a few of these genes - Oct3/4, Sox2, KLf4, and c-Myc -into mouse somatic cells (fibroblasts) by retroviral vectors and culturing the cells for a few weeks, the cells could be reprogrammed to a pluripotent state resembling that of ES cells, which can be differentiated into cells of various types in the body. His team first reported his success with mouse iPS cells in 2006 and human iPS cells in November 2007. (Source: Center for iPS Cell Research and Application, Kyoto University)
How Has iPS Cell Safety Been Improved?
After the first breakthrough, CiRA researched various generation methods and have succeeded in establishing a generation method with higher levels of safety. This was achieved, for instance, by using the L-Myc gene to replace the c-Myc gene, which was thought to increase the risk of carcinogenesis, and by using episomal plasmids to successfully generate human iPS cells without the use of viral vectors, which are thought to cause cancer by damaging the original genome. (Source: Center for iPS Cell Research and Application, Kyoto University)
How are iPS Cells Different (from ES Cells)?
Human embryonic stem (ES) cells are established by removing cells from a 6-7 day old embryo and growing them in culture. In contrast, induced pluripotent stem cells can be generated using cells from an adult body, such as skin, which are plentiful and harmless to remove. As this does not require the destruction of an embryo, it avoids many of the ethical issues that surround human ES cells. Furthermore, unlike human ES cells, it is possible to derive patient-specific iPS cells and induce them into differentiated cells of various types, which can then be transplanted back into the patient without risk of immune rejection. (Source: Center for iPS Cell Research and Application, Kyoto University)
Are there other methods for generating iPS Cells?
Labs around the world are working on new methods to induce pluripotency. For example, simultaneous to the report of human iPS cells by the Shinya Yamanaka group, Professor James Thomson's group in the United States reported a technique for making human iPS cells using a slightly different combination of genes - Oct3/4, Sox2, Nanog and Lin28. A number of other groups have used different viral vectors, such as lentiviruses and adenoviruses, substituted genes with chemicals, and used recombinant proteins. (Source: Center for iPS Cell Research and Application, Kyoto University)
How Can iPS Cells Advance Regenerative Medicine?
It is thought that iPS cells will be useful in elucidating the causes of disease, developing new drugs, and in cell transplantation therapy and other forms of regenerative medicine. Regenerative medicine is a therapy aimed at restoring functions lost through disease or injury. Regenerative medicine in the case of diabetes mellitus, for example, involves transplanting cells with the ability to regulate blood sugar level, or in the case of traumas where nerves have become severed, transplanting nerve cells that can help restore the interrupted connection. iPS cells could be used to make these transplanted cells. (Text and Photo Source: Center for iPS Cell Research and Application, Kyoto University)
How Has iPS Cell Research Advanced?
Compared to 2006, when the generation of iPS cells was first announced, iPS cell research has made great progress. Among its achievements have been advancing research to establish standards for iPS cells, establishing methods of creating safe iPS cells, and confirming therapeutic effects and safety using laboratory animals. Researchers in Japan and overseas are continuing their research to bring new medical treatments using iPS cells to as many patients as possible as soon as possible. (Source: Center for iPS Cell Research and Application, Kyoto University)
How Are iPS Cells Being Used?
In 2014, a clinical research began to transplant iPS cell-derived retinal cells made from the patient's somatic cells into patients with age-related macular degeneration. In 2018, a clinical trial began to transplant dopamine-producing neuronal cells made from iPS cell stock for regenerative medicine into patients with Parkinson's disease. Research is also underway to discover drugs for intractable diseases using iPS cell-derived cells made from patients' cells: in 2017, a clinical trial began for a candidate drug for FOP (progressive ossifying fibrodysplasia), in 2019, for amyotrophic lateral sclerosis (ALS) patients, and in 2020, a familial Alzheimer's disease patients. (Source: Center for iPS Cell Research and Application, Kyoto University)