Pluripotent stem cells (PSCs) have the capacity to undergo self-renewal indefinitely through cell division to form unaltered daughter cells. They can also undergo differentiation to produce different types of cells and tissues of the body. Through cell division, PSCs can develop into three primary germ layers of the early embryonic stage which later develops into the different types of cells in the adult body. The ectoderm forms the skin and nervous system; the endoderm forms the gastrointestinal and respiratory tracts, liver, pancreas, and endocrinal glands; and, the mesoderm forms bone, cartilage, connective tissues, muscles, circulatory system, and urogenital system. However, PSCs cannot differentiate into embryonic tissues such as the placenta.
PSCs can be classified into embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). iPSCs can be obtained by reprogramming differentiated adult somatic cells through an in vitro technology known as cell reprogramming. ESCs are obtained from the inner cell mass (ICM) of a blastocyst. Both ESCs and iPSCs are capable of giving rise to the three germ layers and can be expanded indefinitely.
The capacity to self-renew and pluripotency makes ESCs and iPSCs attractive candidates for the treatment of various diseases and pathological conditions, including regenerative medicine and other cell-based therapies. Since iPSCs are obtained from the patient’s own body, they are genetically compatible and can help to avoid risks of tissue or organ transplant rejection. iPSCs also help in understanding the development and progression of diseases. The versatility of CRISPR/Cas9 based genome editing and indefinite self-renewal and differentiation capacity has opened a new frontier in stem cell research and disease modelling.
However, somatic mutations have been observed in iPSCs, e.g., UV radiation-induced mutations have been reported in skin-derived iPSCs. Other classes of somatic mutations identified in iPSCs are clonal, subclonal, and copy number alterations. These chromosomal aberrations can be linked to cancer-related point mutations in human PSCs, thus affecting their tumorigenicity. Therefore, the presence of mutations in PSCs challenges the safety of their therapeutic applications and warrants a careful assessment of the risks.