Stem Cells
Stem cells which are capable of differentiating into a diverse range of specialized cell types, are cells found in most, if not all, multi-cellular organisms and it differs from other kinds of cells in the body and. All stem cells, regardless of their source, have three general properties in that they are capable of dividing and renewing themselves through mitotic cell division for long periods and that they are unspecialized and can give rise to specialized cell types. As such stem cells are strictly characterized by their ability to renew themselves.
View this video for a better understanding of stem cells.Research into the stem cell field first started off in the 1960s by two Canadian scientists Ernest A. McCulloch and James E. Till and it subsequently grew on further with the advancement of interest into how stem cells could assist in tissue and organ repairs. A new field of scientific and therapeutic endeavor has been created by the discovery and elucidation of the properties of stem cells. The body uses certain key cells known as tissue-derived stem cells to produce all the functional mature cell types found in normal organs of healthy individuals. The term "stem cells" has been applied to many ill-defined cell populations by the media and, indeed, by scientists in some case.
Unlike muscle cells, blood cells, or nerve cells which do not normally replicate themselves, stem cells may replicate many times. Cells replicate themselves many times over through a process called proliferation where a starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.
Stem cells are unspecialized. One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. A stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell); it cannot carry molecules of oxygen through the bloodstream (like a red blood cell); and it cannot fire electrochemical signals to other cells that allow the body to move or speak (like a nerve cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells.
Stem cells can give rise to specialized cells. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. Scientists are just beginning to understand the signals inside and outside cells that trigger stem cell differentiation. The internal signals are controlled by a cell’s genes, which are interspersed across long strands of DNA, and carry coded instructions for all the structures and functions of a cell. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the micro-environment.
Mammalian stem cells are comprise of two types namely embryonic stem cells that are found in blastocysts and adult stem cells that are commonly found in adult tissues.
In a developing embryo, stem cells can differentiate via the process called differentiation into all of the specialized embryonic tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin or intestinal tissues.
As stem cells can now be grown and have the potential to be transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture, their use in medical therapies has been thoroughly scrutinized. Autologous embryonic stem cells generated through therapeutic cloning, and highly plastic adult stem cells from the umbilical cord blood or bone marrow are touted as promising candidates in the field of embryonic cell lines potential.
Stem cells, in classical definition, must possess two properties which are:-
- Self-renewal
The ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
- Potency
The capacity termed as potency to differentiate into specialized cell types of the stem cell, in the strictest sense, requires stem cells to be either totipotent or pluripotent which is to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells.
Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent and these cells can differentiate into embryonic and extraembryonic cell types. On the other hand, pluripotent stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three germ layers. Meanwhile multipotent stem cells can produce only cells of a closely related family of cells such as hematopoietic stem cells differentiating into red blood cells, white blood cells, and platelets. Uipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells such as the muscle stem cells.
Stem cells are identified by their functional ability to regenerate tissue over a lifetime. The bone marrow or hematopoietic stem cell (HSC) has that ability to transplant one cell and save an individual without HSCs in which case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, where single cells are characterized by their ability to differentiate and self-renew. On the other hand, stem cells can be isolated based on a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst (early stage embryo of 5 days old and consisting about 50-150 cells) or earlier morula stage embryos. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers namely ectoderm, endoderm and mesoderm. By this, it means they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. Nevertheless, they do not contribute to the extra-embryonic membranes or the placenta.
Most researches to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF). Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2). Without optimal culture conditions or genetic manipulation, embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and SOX2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency. The cell surface antigens most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. There is still much to be learnt on the molecular definition of a stem cell including many more proteins and continues to be a topic of research of the future.
After nearly so many years of research, there are no approved treatments or human trials using embryonic stem cells. ES cells, being pluripotent cells, require specific signals for correct differentiation and if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face. Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.
On the other hand, adult stem cell refers to any cell which is found in a developed organism that has two properties: the ability to divide and create another cell like itself and also divide and create a cell more differentiated than itself. Also known as somatic (from Greek Σωματικóς, "of the body") stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults.
Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood. A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential. In mice, pluripotent stem cells are directly generated from adult fibroblast cultures. Unfortunately, many mice don't live long with stem cell organs.
Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.). Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants. Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses. The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, because in some instances adult stem cells can be obtained from the intended recipient, (an autograft) the risk of rejection is essentially non-existent in these situations. Consequently, more US government funding is being provided for adult stem cell research.
To ensure self-renewal, stem cells undergo two types of cell division. Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitor cells are cells that have already developed from the stem cells, but can still produce one or more types of mature cells within an organ. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies under the category of induced plriipotent stem cell in Drosophila germarium have identified the signals dpp and adherins junctions that prevent germarium stem cells from differentiating. The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include several transcription factors including the oncogene c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent. However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.
What holds for the future of stem cells? Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease. A number of adult stem cell therapies already exist, particularly bone marrow transplants that are used to treat leukemia. In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases including cancer, Parkinson's disease, spinal cord injuries, Amyotrophic lateral sclerosis and muscle damage, amongst a number of other impairments and conditions. However, there still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research, and further education of the public.
Stem cells, however, are already used extensively in research, and some scientists do not see cell therapy as the first goal of the research, but see the investigation of stem cells as a goal worthy in itself. There exists a widespread controversy over human embryonic stem cell research that emanates from the techniques used in the creation and usage of stem cells. Human embryonic stem cell research is controversial because, with the present state of technology, starting a stem cell line requires the destruction of a human embryo and/or therapeutic cloning. However, recently, it has been shown in principle that adult stem cell lines can be manipulated to generate embryonic-like stem cell lines using a single-cell biopsy similar to that used in preimplantation genetic diagnosis that may allow stem cell creation without embryonic destruction. It is not the entire field of stem cell research, but the specific field of human embryonic stem cell research that is at the centre of an ethical debate.
Opponents of the research argue that embryonic stem cell technologies are a slippery slope to reproductive cloning and can fundamentally devalue human life. Those in the pro-life movement argue that a human embryo is a human life and is therefore entitled to protection. Contrarily, supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It is also noted that excess embryos created for in vitro fertilization could be donated with consent and used for the research. The ensuing debate has prompted authorities around the world to seek regulatory frameworks and highlighted the fact that stem cell research represents a social and ethical challenge.
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