10.12:
Induced Pluripotent Stem Cells
Induced pluripotent stem cells, iPSCs, are mature, differentiated cells, such as skin cells, that are reprogrammed in the laboratory to be similar to undifferentiated embryonic stem cells. That is, they divide and are pluripotent, able to produce any cell type in the body. For example, retinal cells that could be used to replace damaged retinal tissue.
To create iPSCs, mature cells, like skin fibroblasts, are taken from a patient and put into culture. Then, typically, genes for transcription factors, are delivered by viral vectors into the cell nuclei, where they are incorporated into the genome.
The transcription factors then turn on genes that are expressed by embryonic stem cells. Effectively, dedifferentiating them and bringing them to a pluripotent state.
The cells can now divide, and ideally, be directed to produce a specific cell type in culture. The new cells could then be transplanted back into the patient to treat damage or disease with minimal risk of rejection, because they originated from the patient's own cells.
10.12:
Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore called induced pluripotent stem cells (iPSCs).
iPSCs are potentially valuable in medicine, because a patient who needs a particular cell type—for instance, someone with a damaged retina due to macular degeneration—could receive a transplant of the required cells, generated from another cell type in their own body. This is called autologous transplantation, and it reduces the risk of transplant rejection that can occur when tissues are transplanted between individuals.
The Process
To create iPSCs, mature cells such as skin fibroblasts or blood cells from a person are grown in culture. Then, genes for multiple transcription factors are delivered into the cells using a viral vector, and the transcription factor proteins are expressed using the cell’s machinery. The transcription factors then turn on many other genes that are expressed by embryonic stem cells, returning the cells to an undifferentiated, proliferative, and pluripotent state.
It is still being studied whether iPSCs are truly equivalent to embryonic stem cells, but they appear to be similar and can produce cells from all three germ layers of the body. As with other types of stem cells, scientists are learning how to promote the differentiation of specific cell types from iPSCs efficiently, so that the needed cell types can be produced in adequate quantities.
Early Clinical Trials
The first clinical trial transplanted retinal cells derived from iPSCs into patients with age-related macular degeneration. Since then, several iPSC clinical trials have been approved for the treatment of Parkinson’s disease, heart disease, and spinal cord injury. Cells taken from patients and turned into iPSCs are also being used to study their diseases in the laboratory. In general, iPSCs provide another source of stem cells for scientific research.
Suggested Reading
Hamazaki, Takashi, Nihal El Rouby, Natalie C. Fredette, Katherine E. Santostefano, and Naohiro Terada. “Concise Review: Induced Pluripotent Stem Cell Research in the Era of Precision Medicine.” Stem Cells (Dayton, Ohio) 35, no. 3 (March 2017): 545–50. [Source].