Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) are mature, differentiated cells like skin fibroblasts that have been reprogrammed in the laboratory to behave like embryonic stem cells. Unlike ordinary mature cells that stop dividing, iPSCs are pluripotent—they can divide and produce any cell type in the body. This reprogramming reverses the normal differentiation process, returning cells to an undifferentiated, proliferative state.

To create iPSCs, mature cells such as skin fibroblasts are grown in culture. Genes for transcription factors are then delivered into the cells using viral vectors and incorporated into the genome. These transcription factors activate genes normally expressed by embryonic stem cells, effectively dedifferentiating the mature cells and returning them to a pluripotent state capable of division.

Transcription factors are proteins that turn on specific genes. In iPSC creation, transcription factor genes are delivered into mature cells where they activate genes expressed by embryonic stem cells. This gene activation triggers the dedifferentiation process, converting specialized cells back into an undifferentiated, pluripotent state capable of producing multiple cell types.

iPSCs enable autologous transplantation, where patients receive cells derived from their own body. Since the transplanted cells originate from the patient's own tissues, there is minimal risk of transplant rejection. For example, patients with macular degeneration could receive retinal cells generated from their own skin cells, providing personalized treatment with reduced complications.

The first iPSC clinical trial transplanted retinal cells into patients with age-related macular degeneration. Since then, iPSC trials have been approved for treating Parkinson's disease, heart disease, and spinal cord injury. Additionally, iPSCs derived from patients are used to study diseases in the laboratory, providing another valuable source of stem cells for scientific research.

Viral vectors are delivery vehicles used to introduce transcription factor genes into mature cells. These vectors carry the reprogramming genes into the cell nuclei, where they integrate into the genome. Once incorporated, the transcription factor genes are expressed using the cell's own machinery, initiating the dedifferentiation process that converts mature cells into pluripotent stem cells.

Yes, iPSCs are pluripotent and can theoretically produce all cell types in the body, including cells from all three germ layers. Scientists are actively learning how to efficiently direct iPSCs to differentiate into specific cell types in culture, such as retinal cells or neural cells, so that needed cell types can be produced in adequate quantities for therapeutic use.