D. Blicq dblicq@rrc.mb.ca
Nov. 2006 (update 01/04/2010) DIRECTORY I BIO I NOTICE BOARD
All stem cells have two core properties: self-propagation (replication) and unlimited differentiation. This means these
cells can not only continue to replicate and grow more cells, but that they can also differentiate or become virtually any cell type. The medical potential of cells with these two characteristics is tremendous! To a certain extent, cells with no restrictions on the number of times they may replicate have a potential for cellular immortality (within certain limitations).
Propagation / Replication
Stem cells possess the ability to go through multiple cell divisions while still retaining their undifferentiated state. This means many cells can be grown (from a unicellular starting point) to replace, repair or otherwise supplement existing tissues and cell functions. This "cellular immortality" is a fundamental advantage over normal cells with a finite lifecycle. This continuous growth capability is not dissimilar to cancerous cells where unrestricted cellular growth can cause tumor development. An understanding of the cellular mechanisms which induce and inhibit cellular proliferation is an active goal of many cellular researchers.
Differentiation
Stem cells possess (in varying degrees) the ability to differentiate into multiple cell types. Although this characteristic has significant medical p
otential, there are various levels of differentiation which are possible for different classes of stem cells. The phenomena and extent of stem cell differentiation is described as "potency" with several levels of potency occurring naturally.
True stem cells can differentiate into any mature cell type. There are two types of cells which fall into this category, totipotent (no restrictions on differentiation) and pluripotent (some / limited restrictions) on cellular differentiation.
Overall, different types of stem cells may have variable potency - as seen in an ability to make all cell types, many cell types, or even a single cell / tissue type. The similarities and differences between the varying levels of stem cell potency are compared below.
Totipotent Stem Cells
Totipotent stem cells have no limits on differentiation and replication. A sperm-fertilized egg, as well as the first few subsequent generations of cellular division (the morula) produce absolutely totipotent stem cells. These cells can differentiate and become any required mature cell in an organism in any quantity. It is these cells which represent the raw material of life itself and respond to genetic information to establish unique and complex tissues, organs and organisms. The first structure the initial totipotent stem cells create is the blastocyst, a spherical pre-embryonic cell mass which goes on to form the placenta and embryo. The outer cells making up the spherical structure of the blastocyte are also totipotent with unlimited differentiation capability. (refer to the figure below).
http://www.regenetech.com/graphics/primer1.gif
Pluripotent Stem Cells
While the outer cells of the blastocyst go on to form the placenta, the inner mass cells on the interior of the of the blastocyte are considered pluripotent. These pluripotent cells are the products of the original totipotent cells and can form a range of cell types and tissues but do not have the universal differentiation capability. Examples include pluripotent cells forming cells and tissues of the nervous, immune, circulatory system.
Multipotent Stem Cells
These stem cells that can create a limited number of other cell types. An example is found in blood stem cells which form multiple types of blood cells but can no longer form other tissues.
In one sense they become dedicated to establishing a particular type of cell or tissue.
Unipotent Cells
Unipotent cells have the ability to differentiate but only into one type of tissue. Cells of the epidermis (skin) demonstrate this property - continuous regeneration, but of the same tissue type.
Progenitor Cells
Progenitor cells are related to stem cells but can have a limited (or partially limited) capacity for renewal as well as variable levels of dedication to creating a specific tissue type (such as for a specific tissue, organ, or system). Functionally this means a limit on the number of replications and an eventual commitment to a specific tissue type as a mature cell,. Although they have many characteristics that they share with true stem cells there are a number of differences.
he following figure illustrates the differences between the various types of stem and progenitor cells:
http://www.thebiotechclub.org/industry/emerging/images/stemcells2.gif
Replication and Cellular Division of Stem Cells
Self-replication is a defining aspect of stem cells. There are two distinctly different types of self replication which can occur - symmetrical and asymmetrical division.
Symmetrical Replication - in this type of division a single "parent" stem cell divides to create to identical "daughter cells". These progeny / daughter cells are identical to the parent stem cell and possess all the same replicative and potency characteristics.
Asymmetrical Replication - in this type of replication there are two different products from the dividing stem cell. The first is an exact copy of the parental stem cell with all characteristics intact. The second cell is a progenitor cell that has limits on replication and will eventually differentiate into a terminal (final) cell type.
http://www.umdnj.edu/gsbsnweb/stemcell/images/hot-topics-cancer.jpg
Stem Cell Regulation and miRNA (microRNA)
It is unclear what cellular mechanisms are involved in initiating the growth of quiescent stem cells nor is it understood
what causes these cells to cease replication. Recent research has indicated a role for microRNA (miRNA) as a potential signal mechanism. These miRNAs are single-stranded molecules of RNA approximately 20-24 nucleotides long believed to regulated expression of other genes. In general these molecules are believed to have a significant role in cellular development and signaling. These miRNAs are transcribed from DNA but do not have a translational protein product - instead they are produced as small loop molecules often complementary to the mRNA (messenger RNA) they are believed to regulate. Recent work by S.D. Hatfield (2005) indicates a role for miRNA as a means of by-passing normal limits on replication. Other studies have indicated miRNAs have role in causing partial expression, stimulation and inhibition of gene expression:
http://mcb.berkeley.edu/faculty/images/fig1_blurb-3.jpg
Overall there are several identified stages in miRNA function. Primary transcripts of miRNA and converted to mature microRNA by two restriction RNase III restriction enzymes "Drosha" and "Dicer" (Förstemann et al). Primary transcripts of miRNA are converted first by Drosha to produce "precursor" miRNA while the "Dicer" restriction enzyme produces mature miRNA.
The study of the role of miRNA in altering the translational (protein synthesis) process is a high priority for many research groups. An enhanced understanding of the mechanisms of regulation for stem cells may well supply critical information to fight tumor growth in diseases such as cancer. The ability to employ microRNA (either natural or synthetic) to selectively stimulate or inhibit aberrant gene expression may well be a highly useful therapy in the future.
