iPS cells (induced pluripotent stem cells) were established by Shinya Yamanaka in mice in 2006 and in humans in 2007, earning him the 2012 Nobel Prize in Physiology or Medicine. This revolutionary discovery opened a new era of regenerative medicine, disease modeling, and drug discovery.
Basic Knowledge
Stem cells are cells that possess both self-renewal ability and pluripotency (the ability to differentiate into various types of cells).
ES cells (embryonic stem cells): Produced from the blastocyst (inner cell mass) that develops from a fertilized egg. They have pluripotency, meaning that they can differentiate into all types of somatic cells. Because producing human ES cells involves destruction of a human embryo, there are ethical issues.
iPS cells (induced Pluripotent Stem cells): Stem cells produced by introducing four transcription factors (Oct3/4・Sox2・Klf4・c-Myc = Yamanaka factors) into somatic cells such as skin fibroblasts to reprogram them. They have pluripotency equivalent to that of ES cells, while they can be produced from a patient's own cells, lowering the risk of immune rejection.
Applications include cell-transplantation treatments for Parkinson's disease, myocardial infarction, and spinal cord injury; disease models made from patient-derived iPS cells; and drug screening.
Answer: Both have equivalent pluripotency and can differentiate into almost all somatic cells. Regarding ethical issues, ES cells are produced by destroying an embryo (a potential future individual), creating bioethical concerns, whereas iPS cells are produced from somatic cells and therefore raise fewer ethical concerns. The risk of immune rejection is high for ES cells because they come from another individual, whereas it is low for iPS cells because they can be made from the patient's own cells. Challenges of ES cells include ethical issues and rejection; challenges of iPS cells include tumor formation risk (because cancer genes such as c-Myc are used) and low production efficiency.
- iPS cells = produced from somatic cells + Yamanaka factors (Oct3/4・Sox2・Klf4・c-Myc)
- Shinya Yamanaka = 2012 Nobel Prize in Physiology or Medicine (shared with Gurdon)
- ES cells = produced from the inner cell mass of a blastocyst; ethical issues exist
- iPS cells = derived from somatic cells; little rejection; risk of tumor formation
- Pluripotency = the ability to differentiate into cells throughout the body
- Reprogramming = returning a differentiated cell to a pluripotent state by resetting it
Practice
- Name all four Yamanaka factors and explain the significance of their being transcription factors.
- State the advantages of a "patient-derived disease model" using iPS cells.
- Explain one strategy for reducing the risk of tumor formation in clinical applications of iPS cells.