Cells that have the ability to self-replicate and to give rise to mature cells. The concept of stem cells was originally based on renewing tissues. Many adult tissues, such as the skin, blood, and intestines, consist of mostly mature and short-lived cells that must be continuously replaced. Stem cells were postulated as the source of the self-renewal.

In the early 1960s, Canadian scientists Ernest A. McCulloch and James E. Till provided the first experimental proof of the existence of stem cells in the blood system. They revealed that a type of cell in bone marrow possesses the capacity to replicate itself and to differentiate to various lineages of mature blood cells. Self-renewal, together with the capacity for differentiation, defined the properties of stem cells. This definition is generally used in stem cell biology today.