Stem cells are characterized by two properties: (1) the ability to self-renew and (2) the ability to differentiate into different types of cells. Stem cells are often categorized as (1) totipotent, (2) pluripotent, (3) multipotent, or (4) unipotent. Totipotent stem cells can differentiate into the three germ layers (endoderm, ectoderm, and mesoderm), germ cells (oocyte and sperm), and placental cells. Pluripotent stem cells, unlike totipotent, can differentiate into all cell types in the embryo but cannot give rise to placental cells. Multipotent stem cells are lineage-restricted based on the organ of origin (e.g., hematopoietic stem cells only become blood cells), and unipotent cells have the ability to become only one cell type (e.g., in the testes spermatogonia give rise only to sperm).
Stem cells are found throughout the life cycle in embryos, fetuses, and adults. Fetal and adult stem cells, which are multipotent, include umbilical cord stem cells, hematopoietic stem cells, and mesenchymal stem cells. Adult stem cells have the ability to replenish tissue or repair damage throughout adulthood. Most adult stem cells are difficult to obtain, but adipose stem cells and mesenchymal stem cells can be relatively easily extracted from fat tissue and bone marrow. One particular study used mesenchymal stem cells for acute toxicity testing of 12 Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) recommended chemicals, and the results were compared to other cell lines including 3T3 mouse fibroblasts and normal human keratinocytes (NHK). Results showed that human mesenchymal stem cells are just as, if not more, sensitive than 3T3 and NHK at predicting globally harmonized system (GHS) categories. However, fetal and adult stem cells are more difficult to adapt to toxicity assays than pluripotent cells since they usually divide slowly, can be passaged in vitro a limited number of times, are often hard to obtain, and have limited differentiation abilities.