Ever wondered how does a complex multicellular organism develop out of a single zygote after the fertilization? This question took years for scientists to figure out and the answer came to be known in form of Stem Cells. The understanding of Stem cells have revolutionized the field of health, medicine and understanding of biology and evolution on whole.
The existence of haematopoietic stem cells were first postulated by Russian histologist Alexander Maksimov in 1908. Almost after 50 years, another group of scientists reported stem cell activity in the brain. However, it was not until 80s that major breakthrough was obtained by deriving embryonic stem cells from Mouse. This led to extensive in-vitro study of stem cells and important concepts were established.
Stem cells are undifferentiated biological cells that have the remarkable property to develop ( differentiate ) into specialized cell types and can divide ( by mitosis ) to produce more stem cells. Stem cells differ from other cell types by two important characteristics :
- Self-renewal: the ability to go through numerous cycle of cell division while maintaining the undifferentiated state.
- Potency: the capacity to differentiate into specialized cell types. Stem cells are further classified are totipotent, pluripotent, multipotent or unipotent based on the types of cells they differentiate into.
In mammals, scientists have classified stem cells into two broad categories - embryonic stem cells and non-embryonic adult or somatic stem cells.
Embryonic Stem Cells: These cells are isolated from the inner cells mass of blastocysts ( a 3-5 day old human enmbryo ). The embryos used for obtaining these cells are created for reproductive purposes through in vitro fertilization procedures. They are not derived from eggs fertilized in a woman's body. In order to study the process of division and differentiation of embryonic stem cells, it is necessary to culture them in vitro. These cells are generated by transferring cells from a preimplantation-stage embryo ( the embryo which has not yet implanted itself into the wall of uterus ) into a plastic laboratory culture dish that contains a nutrient. The cells divide and spread over the surface of the dish. The inner surface of the culture dish is typically coated with mouse embryonic skin cells that have been treated not to divide. This coating of the cells is called feeder layer. The mouse cells in the bottom of the culture dish provide the cells a sticky surface to which they can attach and also release nutrient into the culture medium. Although there are methods to grow stem cells without feeder layer too. If the plated cells survive, divide and multiply enough to crowd the dish, they are removed gently and plated into several fresh culture dishes. The process of re-plating or subculturing the cells is repeated many times and for many months. Each cycle of subculturing the cells is referred to as a passage. Once the cell line is established, the original cells yield millions of embryonic stem cells. The embryonic stem cells that can proliferate in cell culture for a longer period of time without differentiating but have the ability to give rise to nearly all kind of body cells i.e. cells derived from any of the three germ layers are called pluripotent stem cells.
Adult Stem Cells: An adult stem cell is thought to be an undifferentiated cell, found among differentiated cells in a tissue or organ that can renew itself and can differentiate to yield some or all of the major specialized cell types of the tissue or organ. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Scientists also use the term somatic stem cell instead of adult stem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs). Unlike embryonic stem cells, which are defined by their origin , the origin of adult stem cells in some mature tissues is still under investigation.
Adult stem cells have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis. They are thought to reside in a specific area of each tissue (called a "stem cell niche"). In many tissues, current evidence suggests that some types of stem cells are pericytes, cells that compose the outermost layer of small blood vessels. Stem cells may remain quiescent (non-dividing) for long periods of time until they are activated by a normal need for more cells to maintain tissues, or by disease or tissue injury.
Eg.,
- Hematopoietic stem cells give rise to all the types of blood cells.
- Epithelial stem cells in the lining of the digestive tract occur in deep crypts and give rise to several cell types.
- Neural stem cells in the brain give rise to its three major cell types: nerve cells (neurons) and two categories of non-neuronal cells.
Transdifferentiation - A number of experiments have reported that certain adult stem cell types can differentiate into cell types seen in organs or tissues other than those expected from the cells' predicted lineage (i.e., brain stem cells that differentiate into blood cells or blood-forming cells that differentiate into cardiac muscle cells, and so forth). This reported phenomenon is called transdifferentiation.
It is very difficult and challenging for scientists to come up with exact conditions and medium that maintain the particular differentiated or non differentiated state of the stem cells. Until very recently, In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be 'reprogrammed' genetically to assume a embryonic stem cell like state i.e. have the ability to give rise to any kind of cell. This new type of stem cells are called Induced pluripotent stem cells (IPSCs). Using genetic reprogramming with protein transcription factors, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue.
There are many ways in which stem cells can be used in research and clinic.
- Cancer and birth defects, are due to abnormal cell division and differentiation. Understanding the mechanism with which stem cells are able to differentiate would help us to control these diseases on a wider scale.
- Testing of new drugs is also an important field of application. For example, new medications could be tested for safety on differentiated cells generated from human pluripotent cell lines. Cancer cell lines for example are already sed to screen potential tumor drugs.
- Cell-based therapies are probably the most important application of human stem cells.Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.
Although much work has been done in the past, a lot of questions are yet unexplored and beyond our current understanding. We still don't have clear idea of how stem cells divide or what are the genes that play critical role in maintaining the potency or self-renewal ability. What are the conditions under which these cells differentiate or why do they reduce to so low in numbers after development of organism? This is a interesting and debatable area of interest in Life sciences and lot of energy is being put into it. Some notable works are :
- 2014: Adult mouse cells reprogrammed to pluripotent stem cells using stimulus-triggered acquisition of pluripotency (STAP);[108] a process which involved bathing blood cells in an acid bath (pH 5.7) for 30minutes at 37°C.
- 2013: Scientists at Scotland's Heriot-Watt University developed a 3D printer that can produce clusters of living human embryonic stem cells, potentially allowing complete organs to be printed on demand in the future.
- 2012: Katsuhiko Hayashi used mouse skin cells to create stem cells and then used these stem cells to create mouse eggs. These eggs were then fertilized and produced healthy baby offspring. These latter mice were able to have their own babies.
- 2011: Israeli scientist Inbar Friedrich Ben-Nun led a team which produced the first stem cells from endangered species, a breakthrough that could save animals in danger of extinction.
- 28 May 2009 Kim et al. announced that they had devised a way to manipulate skin cells to create patient specific "induced pluripotent stem cells" (iPS), claiming it to be the 'ultimate stem cell solution'.
A more exhaustive list can be obtained from the list of references.
- https://en.wikipedia.org/wiki/Stem_cell
- http://stemcells.nih.gov
- http://hsci.harvard.edu/
- https://sciencedirect.com/
Compiled by Vivek Rai, while Amit Kumar didn't write a single word and just idled on Facebook.