ESCs

Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a preimplantation embryo, typically a blastocyst about 3–5 days after fertilization in humans. They have the ability to self-renew indefinitely in culture and to differentiate into all cell types of the three germ layers.

Because of their pluripotency, ESCs are used in basic research to study early development and in applied research for regenerative medicine, disease modeling, and drug screening. They are characterized by expression of transcription factors such as Oct4, Sox2, and Nanog, and by surface markers; their pluripotent state is maintained in culture using signals that promote self-renewal.

Derivation and culture: human ESCs are derived from surplus IVF embryos with informed consent. Mouse ESCs have a longer history and were traditionally cultured with leukemia inhibitory factor (LIF) and serum on feeder cells, though defined, feeder-free conditions exist. Human ESCs typically require basic fibroblast growth factor (bFGF) and defined matrices. ESCs can exist in different developmental states, with mouse lines commonly described as naive and human lines as primed.

Applications and challenges: ESCs offer potential to replace damaged tissues, including retinal, neural, and cardiac tissues, and have shown progress in animal models and in several clinical trials in various indications. Safety concerns include the risk of teratoma formation, immune rejection, and genetic or epigenetic instability. Ethical and legal debates surround embryo use, which has spurred development of alternatives.

In addition, ESCs are ethically debated; induced pluripotent stem cells (iPSCs) generated by reprogramming adult somatic cells offer an alternative that avoids embryo use and can be patient-specific.