Advantages and Disadvantages of Using Human Embryonic Stem Cells Versus Induced Pluripotent Stem Cells in Cell Therapy

Cell therapy has emerged as a promising field in regenerative medicine, holding the potential to treat a variety of diseases. However, the use of human stem cells, particularly human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), presents unique advantages and disadvantages.

Overview of hESCs and iPSCs

Human embryonic stem cells (hESCs) are derived from the inner cell mass of a blastocyst, while induced pluripotent stem cells (iPSCs) are created by reprogramming adult cells using four key genes. This process can lead to the activation of oncogenes and other unintended effects.

Advantages of hESCs

Genomic Integrity: One of the primary advantages of hESCs is their intact genomes, which means they do not undergo the insertional mutagenesis seen in iPSCs. This reduces the risk of unforeseen genetic modifications.

No Epigenetic Changes: hESCs also do not have epigenetic changes, which are common in iPSCs. These changes can result from environmental factors such as smoking, sunlight, stress, and pollution.

Disadvantages of hESCs

Immune Rejection: Although hESCs are not "self," they can trigger an immune rejection response, similar to other foreign tissues. This is a significant limitation in clinical applications.

Genetic Instability: Long-term in vitro culture of hESCs can lead to genetic changes, as some cell lines have shown. This poses concerns for their use in therapy.

Advantages of iPSCs

Matching Patient’s Genetic Background: iPSCs are patient-specific, derived from adult cells. This reduces the risk of immune rejection and makes them more suitable for personalized medicine.

Disadvantages of iPSCs

Risk of Off-Target Effects: The process of reprogramming adult cells can activate other genes, including oncogenes. This introduces potential risks in clinical applications.

Epigenetic Modifications: Adult cells have epigenetic changes due to various life stresses, which can affect their quality and viability.

Common Challenges in Cell Therapy

Regardless of whether hESCs or iPSCs are used, both face several common challenges in cell therapy:

Teratoma Formation: When implanted, both hESCs and iPSCs can form teratomas, which are tumorous growths that can be harmful.Time and Efficiency: Differentiation of these cells into specific cell types in vitro is time-consuming, inefficient, and expensive. This complexity limits their use in acute trauma scenarios.Age Limitations: Fetal cell types, which are used in differentiation, may not be suitable for adult tissues, such as heart cells.Single Cell Type Limitations: The differentiated cells from either hESCs or iPSCs can only be used for treatments involving a single cell type, limiting their applications in regenerating tissues like skin, articular cartilage, or kidneys.

Current Clinical Applications

The one tissue currently under clinical trial for stem cell therapy is macular degeneration. This is because only one cell type—retinal cells—is needed, and they can be organized in a sheet.

Conclusion

While both hESCs and iPSCs offer unique advantages in cell therapy, their limitations highlight the need for further research and development. As the field advances, it is expected that the use of stem cells in regenerative medicine will become more effective and safer, ultimately benefiting a wider range of diseases and conditions.