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43.3: Induced Pluripotent Stem Cells

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Cell Biology

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Induced Pluripotent Stem Cells

43.3: Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).

Somatic cells are reprogrammed into iPSCs using viral vectors to deliver the genes encoding Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. There are various ways to confirm the transformation. Among these, checking for teratoma formation is a routinely performed test.  A teratoma is an encapsulated, benign tumor formed by the successfully converted iPSCs, consisting of tissues from all three germ layers– endoderm, mesoderm, and ectoderm. Other characteristics of iPSCs include unlimited proliferation, long telomeres, and expression of pluripotent stem cell markers such as Oct4, c-Myc, and Nanog.

iPSCs are potentially valuable in medicine because a patient could receive a transplant of the required cells generated from another cell type from 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.

Early Clinical Trials

The first clinical trial using iPSCs involved transplanting retinal cells derived from iPSCs into patients with age-related macular degeneration–a disease of the retina affecting normal vision. Since then, several iPSC clinical trials have been approved to treat Parkinson’s disease, heart disease, and spinal cord injury. Cells taken from patients and turned into iPSCs are also used to study their diseases in the laboratory. In general, iPSCs provide another source of stem cells for scientific research.

Limitations and Risks

Generating iPSCs from somatic cells is a long and inefficient process, which may take up to 4 weeks, with only 0.01 to 1% of somatic cells being able to form pluripotent stem cells. Secondly, all the OSKM factors must be expressed in a given cell in optimal amounts to become a  pluripotent one.

The viral vectors for delivering the OSKM factors can introduce the genes in an undesired location in the genome, activating genes that can cause cancer. Similarly, c-Myc is reported to be an oncogene, which, if overexpressed, can also cause cancer. 

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