An Introduction to Pluripotency
Pluripotent: adjective; capable of giving rise to many different cell types. This is the hallmark characteristic of the induced pluripotent stem cell or iPSC. Since the discovery of reprogramming adult human fibroblasts into an induced state of pluripotency in the early 2000s, the scientific community has been enamored with the possibility of this dynamic cell type.1 A seemingly vast universe of possibilities exists for the iPSC from the corners of basic research to the depths of clinical medicine.
The pluripotent state has been proven time and again using various protocols for generating cell types and organoids covering nearly every system in the human body. Industry and pharma have also come to favor the iPSC for many of its other qualities. While the iPSC may be considered a “finicky” cell type to work within the lab, and costly to grow due to reliance on complex growth media and matrices, it is unique in that it is considered to be a patient (or donor) sourced cell type, but with the added potential for long-term growth in culture. Easily derived from primary skin biopsies or blood, iPSCs maintain the existing genetic and epigenetic makeup of the human from which they came without the ethical dilemmas surrounding the use of embryonic stem cells. Nearly as important as their differentiation potential and proximity to the primary source is the ability of iPSC cultures to be scaled and banked for the purposes of manufacturing gene and cell therapies.
In the undifferentiated state, iPSCs have been broadly studied across research fields. They have been pivotal instruments for understanding basic cell biology, advancing drug discovery efforts, and have served as the foundation of clinical therapies. Differentiated but otherwise unmodified iPSCs already began to have a clinical impact within the first decade of their discovery. In 2017, somatic cells harvested from a patient with macular degeneration were converted to iPSCs and differentiated into retinal pigment epithelial cells, which were then used in the same patient in an effort to restore vision as an autologous (self) cell therapy.2 Since then, other clinical uses of autologous stem cell therapies have been investigated for regenerative medicines in the fields of diabetes and cardiology, among others.3,4
Broadening Therapeutic Potential
Today, the use of iPSCs has progressed from regenerative therapies to immunotherapies and other precision medicines. We have already seen the impact of autologous chimeric antigen receptor (CAR) T cells in the clinic where they are used to address hematological malignancies. Autologous therapies avoid concerns over the undesired immune response in patients, because typically, even if the cells are engineered ex vivo they are still recognised as “self” once returned to the patient’s body. However, engineering any cells ex vivo to enable autologous personalised medicine is a time-consuming and expensive process because each dose of the therapy must be engineered on demand for every patient.
