Organ and tissue stem cells are one of two types of true “stem cells.” Because they are found in the organs and tissues of adults, they are often referred to as “adult” stem cells; but they are also found in the organs and tissues of children. More recently, they have been called “distributed stem cells,” because they naturally distribute the constituent cell-type potency of the early embryo. The earliest embryo formed by fertilization is totipotent, meaning that it has the ability to produce every constituent cell type in the mature body. In contrast, tissue stem cells are either uni-potent or multi-potent in a tissue-specific fashion. So, uni-potent adult lens stem cells replenish only one mature cell type that forms the lens of the eye. In contrast, multi-potent small intestinal stem cells replenish several different cells that form the lining of the small intestines. However, neither of these tissue stem cells has the ability to replenish the tissues of each other or any other different organ or tissue. Tissue stem cells have also been identified in birth related tissues like amnion fluid, amnion membranes, the placenta, and the umbilical cord.
Embryonic stem cells (ESCs) are artificially produced from the embryo at the stage when the cells used are no longer totipotent. Because the embryo, which is a living human being, is destroyed by the procedure used to derive human ESCs (hESCs), production and use of these cells remains controversial. When injected into mouse embryos, mouse ESCs (mESCs) show the property of pluripotency, meaning they possess the ability to produce all the cells in the body except those that form the placenta. However, outside of embryos, in cell culture both mESCs and hESCs have been shown to have primarily fetal pluripotency. Though they can be instructed to make many different cell types characteristic of constituent cells at the fetal stage of development, it has proved very challenging to get them to make cells characteristics of the organs and tissues of children and adults.
Induced pluripotent stem cells (iPSCs) have potency properties that are very similar to ESCs. In addition, like ESCs, they do not occur naturally. However, whereas ESCs were made by manipulation of the culture conditions of embryonic cells, the main principle for production of iPSCs is manipulation of the genetic control of mature adult cells. In both cases, the artificial manipulations result in many gene mutations and alterations that compromise the use of the cells for cell therapies. Both form tumors at a high rate.
By the strict definition of “stem cell”, ESCs and iPSCs are not stem cells. They lack the asymmetric self-renewal that defines organ and tissue stem cells. When ESCs and iPSCs are instructed to make constituent cells, they convert to become the next stage of constituent cell production; and their stem properties are lost.
A recently discovered and described second type of stem cells is metakaryotic stem cells. They are found in the developing fetus and divide with asymmetric self-renewal to establish new organs. Curiously, they do not organize their DNA into typical condensed chromosomes for cell division like adult tissue stem cells. Unlike embryonic precursor cells, metakaryotic stem cells can be found in adult tissues, too, though at very low frequencies. Currently, whether a lineage relationship exists between adult tissue stem cells and metakaryotic stem cells is unclear.