All you need to know about the various types of Stem Cells
There has been recent debate about Pluripotent vs Multipotent Stem Cells and what the difference is between the two. Read on as we go in-depth and explain how the various types of Stem Cells differ.
In addition to being able to multiply, divide and produce new versions of themselves (self-renew), stem cells can also differentiate, or specialize, into other cell types.
If the stem cell can form all cell types of the embryo and adult, including germ cells (eggs and sperm) and the extra-embryonic structures found during the pregnancy, such as placenta, it is considered totipotent. A fertilized egg cell, is totipotent, as are some of the early cell masses or blastomeres resulting from cleavage (or division) of the fertilized egg. However, these cells are not stem cells since they do not self-renew.
If a stem cell can do all of these things but is unable to form the extra-embryonic structures (such as parts of the placenta) then it is called pluripotent. Embryonic stem cells are pluripotent.
All other stem cells found in specialized tissues of the fetus or adult are multipotent, meaning that they are able to form many but not all tissue cells of the body, or are unipotent, able to form just one other cell type.
Spermatogonia are cells that can only form sperm and are unipotent. In order to be able to divide without losing its stem cell pool for later use, a stem cell is capable of multiplying by dividing in two, but after each cell division usually one of the two daughter cells retains the original stem cell properties.
The daughter cell that loses stem cell properties (or the ability to differentiate into multiple types of cells or tissues) then becomes a fully differentiated cell, one that is a specialized to produces all of the proteins required for its proper function within the tissue or organ it belongs to.
It can only divide a few times or not at all such as brain cells. To simplify, it is easiest conceptually to divide stem cells into two types: embryonic stem cells and adult Stem Cells.
Embryonic Stem Cells are derived from a very early embryo, and adult stem cells are found in tissues of the baby after birth tissues, not only of the body but also the umbilical cord.
Well both, although until recently, adult Stem Cells are generally considered to be either multipotent or unipotent. In the adult body under normal circumstances, there are no totipotent or pluripotent stem cells. However, under artificial conditions, some Adult Stem Cells, like spermatogonia in the testis, can be converted into stem cells with pluripotent properties.
Under normal circumstances, however, a differentiated cell cannot change back into a Stem Cell since differentiation is a one-way process. Fully differentiated cells can only divide a limited number of times to give rise to new cells with the same characteristics, while differentiation into other cell types is not possible. Similarly, a multipotent or unipotent adult Stem Cell in an organ or tissue, such as the pancreas, cannot normally revert to the pluripotent state of an embryonic cell.
By contrast, Embryonic Stem Cells that are pluripotent, can develop into all cell types in the human body. During embryonic growth and development, when all the different new cell types develop and tissues are formed, most cells gradually lose their Stem Cell characteristics and their ability to differentiate into many different cell types or tissues.
This differentiation process starts when the totipotent fertilized egg moves to the pluripotent state as the inner cell mass of a blastocyst stage in the embryo, then into specialized cells such as the multi- or unipotent Stem Cells of specific organs or tissues. These later Stem Cells are also known as progenitor cells that can divide and are predetermined to differentiate only to the cell types that are needed for the proper function of their own specific organ or tissue.
The biology underlying the one-way process of differentiation is based on epigenetic modifications and mechanisms. Epigenetic modifications are the regulation of gene usage, limiting the specific cell type by permanently inactivating genes not necessary for the mature cell. There are other mechanisms that limit the cell’s differentiation into specific tissues and organs.
The human body is made up of some 220 different types of cells, all of which are descendants of a single fertilized egg. The DNA or genetic material of the egg contains the entire process and material for the development of the embryo. The fertilized egg develops into a blastocyst stage of the embryo within a few days of fertilization. After that, the first division of function between groups of cells takes place and the earliest totipotent cells have disappeared and are replaced by an inner population of 47 pluripotent cells and an outer layer of multipotent cells. This takes place after only three cell divisions when the embryo consists of only eight identical cells.
In the process of in-vitro fertilization when an egg is fertilized outside of the body for implantation at a later date, at the eight-cell stage of development, one single cell can be removed and used for prenatal genetic testing to diagnose specific disease-causing mutations in the embryo. The embryo, consisting only of the remaining seven cells, can go on to develop normally and be transferred to the uterus where, if all goes well, a normal baby will be born. This prenatal genetic testing allows for healthy embryos without lethal genetic diseases to be implanted and demonstrates that the cells of the embryo at this stage are still entirely totipotent with unlimited plasticity.
At the next embryonic stage, known as the blastocyst, the distinction between pluripotency and multipotency becomes clearer. The innermost population of cells is known as the inner cell mass, from which the entire embryo is formed. The outermost cells form the trophectoderm, which makes up parts of the placenta and umbilical cord.
Cells from the inner cell mass are pluripotent and can differentiate into all the different cell types that make up the body but can no longer contribute to placenta tissue. This pluripotent period lasts for only a short time, as cells quickly start to differentiate as development occurs.
If the cells comprising the inner cell mass are removed from an embryo and cultured in a Petri dish in a laboratory, an Embryonic Stem Cell line can be created. Under the right conditions, these cells will continue to divide outside the embryo for an unlimited period of time (in stark contrast to their temporary presence in the embryo) and thus retain their pluripotent characteristics.
Even though most cells differentiate and develop specialized functions after the pluripotent blastocyst stage, a few cells are successful in maintaining, or regaining, their Stem Cell properties. In an adult, most and possibly all organs and tissues contain a small reserve of what we call adult Stem Cells. The most well-known type of Stem Cell that can do this is the blood Stem Cells in the bone marrow.
These Adult Stem Cells are multipotent and can form into a variety of cell types but are generally limited to the organ from which they arise. Stem Cells from the bone marrow can form all cells that constitute the blood, but cannot form nerve cells, intestinal cells, or insulin-producing cells. Adult Stem Cells are distinctly different from Embryonic Stem Cells because they maintain their ability to form one stem cell that can differentiate and divided into one type of cell over the course of an entire lifetime in humans.
In summary, totipotent and pluripotent cells in an early embryo are free to differentiate in any direction. These cells have not acquired specific functions such as insulin production from pancreatic islet cells. They are good at dividing, usually once per day. However, as the cells start to differentiate and specialize, the ability of individual cells to divide and make more cells, decrease.
We hope you have a better understanding of pluripotent vs multipotent vs totipotent Stem Cells and realize the exciting potential that Stem Cells have to offer!
Mummery, C., Stolpe, A., Roelen, B., & Clevers, H. (Eds.). (2014). Stem cells : Scientific facts and fiction (Second ed.). London: Elsevier/AP, Academic Press is an imprint of Elsevier.