What makes a stem cell special
Most of the roughly 200 cell types in the human body are terminally differentiated — a liver cell divides to make more liver cells and nothing else. Stem cells are different: they retain the ability to divide without differentiating (self-renewal) and to produce daughter cells that specialise into multiple lineages.
This is controlled by gene expression: different transcription factors are active in different cell types, switching on the genes needed for that cell's function and silencing the rest. A stem cell maintains a state of open chromatin at many developmental gene loci, preserving the potential to activate different programmes on demand.
The two most important properties for therapy are:
- Pluripotency — the ability to become any of the three embryonic germ layers (ectoderm, mesoderm, endoderm) and all their derivatives.
- Self-renewal — the ability to divide indefinitely while maintaining the undifferentiated state, allowing therapeutic quantities of cells to be produced in the lab.
For background on cell division and how daughter cells receive identical copies of the genome, see our mitosis and meiosis guide.
The iPSC breakthrough
Embryonic stem cells (ESCs) were powerful but controversial — obtaining them required destroying a human embryo. In 2006, Shinya Yamanaka's group at Kyoto University published a result that changed everything: adult mouse fibroblasts (skin cells) could be reprogrammed to an embryonic-like state by introducing just four transcription factors — OCT4, SOX2, KLF4 and c-MYC.
These induced pluripotent stem cells (iPSCs) were indistinguishable from ESCs in their ability to form all cell types, yet they avoided the ethical issues of embryo use. More importantly, patient-derived iPSCs created from someone's own skin or blood cells are genetically matched — eliminating immune rejection. Yamanaka and John Gurdon shared the 2012 Nobel Prize in Physiology or Medicine for this work.
The genetic regulation involved — how transcription factors interact with DNA to control which genes are expressed — is explained in our DNA, genes and heredity guide.
What is already in clinical use
Stem cell therapies have been used clinically for decades in forms most people do not realise are stem cell treatments:
- Haematopoietic stem cell transplantation (bone marrow transplant) — used for over 60 years to treat leukaemia, lymphoma and genetic blood disorders by replacing a patient's blood-forming stem cells with a donor's. Over one million transplants have been performed worldwide.
- Limbal stem cell transplantation — restores sight in patients with chemical or thermal eye burns that have destroyed the corneal stem cells responsible for regenerating the corneal surface. The first successful case was in 1997.
- Cultured epithelial autografts — a patient's own skin stem cells are expanded in the lab and grafted back to treat large burns, severe epidermolysis bullosa and other skin disorders.
CRISPR-edited cell therapy: the next frontier
Combining iPSC technology with CRISPR gene editing creates a transformative workflow:
- Derive iPSCs from the patient's own blood or skin cells.
- Use CRISPR-Cas9 to correct the disease-causing mutation at the DNA level.
- Differentiate the corrected iPSCs into the required cell type.
- Transplant the corrected, patient-matched cells back.
This approach is furthest advanced for haemoglobinopathies (sickle cell disease, beta-thalassaemia). In 2023, the FDA and EMA approved Casgevy (exagamglogene autotemcel) — the world's first approved CRISPR-based medicine — which uses this workflow to correct the haemoglobin mutation in a patient's own haematopoietic stem cells.
For the genetics of inherited blood disorders and the role of alleles in disease inheritance, see our DNA, genes and heredity guide and the mRNA vaccines article for related molecular medicine context.