What are iPSCs?
Induced pluripotent stem cells (iPSCs) are adult (somatic) cells that have been genetically reprogrammed to revert to a pluripotent stem-cell–like state, meaning they can differentiate into almost any cell type of the human body.
They functionally resemble embryonic stem cells (ESCs) but are created without destroying embryos.
Discovery
iPSCs were first developed in 2006 by , who showed that mature cells could be reprogrammed by introducing specific genes. This discovery revolutionised regenerative medicine and earned the 2012 Nobel Prize in Physiology or Medicine.
How are iPSCs Created?
Adult cells (commonly skin fibroblasts or blood cells) are reprogrammed by introducing a set of transcription factors known as Yamanaka Factors:
- Oct4
- Sox2
- Klf4
- c-Myc
These factors reset the cell’s gene expression profile, converting it into a pluripotent state.
Key Characteristics
- Pluripotent: Can differentiate into cells from all three germ layers (ectoderm, mesoderm, endoderm)
- Self-renewing: Can divide indefinitely under lab conditions
- Patient-specific: Can be generated from the patient’s own cells, reducing immune rejection
iPSCs vs Embryonic Stem Cells (ESCs)
| Aspect | iPSCs | Embryonic Stem Cells |
| Source | Adult somatic cells | Inner cell mass of embryo |
| Ethical concerns | Minimal | Significant |
| Immune rejection | Low (autologous) | Higher |
| Clinical acceptability | High | Controversial |
Applications of iPSCs
Regenerative Medicine
- Repair of damaged tissues (heart, spinal cord, retina)
- Cell replacement therapy for degenerative diseases
Disease Modelling
- Study of genetic disorders such as:
- Parkinson’s disease
- Alzheimer’s disease
- Sickle Cell Disease
- Allows “disease-in-a-dish” modelling
Drug Discovery & Toxicity Testing
- Testing drug responses on patient-specific cells
- Reduces reliance on animal testing
Gene Therapy
- Correction of genetic defects using tools like CRISPR-Cas9
- Re-implantation of corrected cells
iPSCs and Sickle Cell Disease
- Patient-derived cells can be reprogrammed into iPSCs
- Genetic mutation corrected using gene editing
- Differentiated into healthy blood stem cells
- Potential for curative autologous therapy
Advantages of iPSCs
- Avoid ethical issues of embryo destruction
- Reduced risk of immune rejection
- Enable personalised medicine
- Unlimited cell supply
Limitations & Risks
- Risk of tumour formation (especially due to c-Myc)
- Genetic and epigenetic instability
- High cost and technical complexity
- Long-term safety still under evaluation
Ethical Dimensions
- Fewer ethical concerns than embryonic stem cells
- Issues remain regarding:
- Genetic manipulation
- Germline modification
- Equity in access to therapies
Regulatory Framework in India
National Guidelines for Stem Cell Research, 2017
- Permits basic and clinical research on iPSCs
- Allows clinical use only through approved trials
- Commercialisation restricted except for approved therapies
National Guidelines for Gene Therapy Product Development, 2019
- Framework for gene-edited cell therapies using iPSCs
- Germline gene editing prohibited
Global Developments
- iPSC-derived retinal cell therapies approved for trials
- Integration with CRISPR for monogenic disorders
- Used in FDA-approved gene therapy pipelines
Way Forward
- Improve reprogramming safety and efficiency
- Reduce costs for scalability in public health
- Strengthen regulatory oversight
- Ensure equitable access to advanced therapies
- Promote indigenous research and clinical translation
