Monday 17 October 2011

Final assignment(Genetically Modified Organism)

Introduction
Developments in molecular biology since the early 1970s have resulted in many different techniques which lead to genetic modification. These techniques have been used in many micro organisms, plants and animals which can help to better understanding in wide variety of science, organisms, their interaction, production, life style, genetics, enzymes and therapeutically agents.
Genetically modified organism (GMO) occurs when genetic material of one organism is altered (DNA or RNA) by applying the scientific technique that leads to create a new organism with new behaviour or characteristic. Alteration of genetic material of organism can transfer to other cells or replication that not occurs naturally in nature. Usually the GMO is accompanying by the removal of DNA from the cell and it’s manipulation outside the cell and reinsertion to the same organism or another one.
In overall, genetically modified organisms are those with altered genetic material which can be plants animals or micro organisms (including bacteria, viruses, parasites and fungi).The technique that applies to GMO is DNA recombinant. Manipulation of DNA outside the cell in DNA recombination and insert of DNA again into the cell can be done by using several ways. The choice of method is usually determined by the type of vector and host cell being used.
There are several ways to insert modified genes into target cell’s organism:
Transformation is the one of the methods that can be used to insert plasmid into cell when cells can take up DNA from the environment. However many cell types do not naturally transform, including yeast, E. coli and mammalian cell but simple chemical treatment can make all of these cell competent, or able to take up external DNA.
Electroporation. In this procedure, electron current uses to microscopic pores in the membrane of cell, then the modified DNA can enter the cell through these pores. Electroporation can be using to all the cell type except those with cell wall which must be converted to protoplas first. Protoplasts are produced by enzymatically removing of cell wall, to directly access to the plasma membrane.
Microinjection Introducing of external DNA into the plant cells is to shoot it directly through thick cellulose walls by using a gene gun.  Beside this methods DNA can be introduced directly into animal cell. This technique needs the glass micropipette with diameter that is less than cell. This micropipette punctures the plasma membrane and DNA can be injected through it.
Thus, there is a variety of different restriction enzymes, vectors and methods of inserting DNA into cell. But foreign DNA will survive only if it is either present on a self replicating vector or incorporated into one of the cell’s chromosomes by recombination.By knowing how cells carrying a particular gene, the gene product are frequently the objective of genetic modification. Most of the earliest work in genetic modification used E. coli to synthesize the gene product. E. coli is easily grown and researcher are very familiar to with this bacterium an its genetics. Beside the E.coli, plants cells genetically modified easily because they can be growth from small pieces of tissue and single cell. Genetically modified organism by biotechnology is very specific and rapid selection process, and genes from another organism can be incorporated into modified corn. Therefore (GMO) techniques and application in human benefit always carries concern for environmental and human health impact.
In this study we are consider the bioethical issues of this genetically modification organism and their products which impact over human’s life.
Therapeutic application of (GMO)
Making gene product by genetic modification is a way which applies by genetic engineer. Nowadays researchers are able to use bacteria, fungi, plants and mammalian cells in the process of genetic modification to produce many therapeutic products. To produce the product it is much more economical that have a modified organism to secrete the product for example: Bacillus subtilis.
These gram positive bacteria are more likely to produce their own product and are industrially proffered. Another microbe that being used as vehicle for experessing genetically engineered genes is baker’s yeast, saccharomyces cerevisiae. This organism is the best understood organism in eukaryotic genome and its genome is four times bigger than E. coli. Furthermore yeast is able to secrete constituently the product. For all of these reasons, yeast have become the eukaryotic workhose of biotechnology. Mammalian cells in culture can be genetically modified like bacteria to produce wide variety of product; this can be happening even in human cells. The best suited for making protein product for medical uses is often in mammalian cell because cells are able to produce their product and have less toxins or allergens. Using mammalian cells to obtain genetic product often needs steps of cloning the gene in bacteria, Cloning stimulating factor (CSF). For example, protein that secrete naturally by white blood cell, (CSF) is very effective due to stimulation of growing certain cells that protect against infections. To make wide amount of (CSF) industrially, the gene must be inserted into the plasmid of the bacteria firstly. This bacterium is used to get many copies of plasmid and finally the recombinant plasmid is inserted to the mammalian cells that are grown into bottle.
In the wide variety usage of mammalian cells, bacteria and yeast cell to generate genetically modified organism, the plant cells also can be grown in culture, altered by recombinant DNA technique to make genetically modified plants. These modified plants can be used in the production of human therapeutic agents, including vaccine and antibodies. The main advantages of using of plants is due to low- cost production using agriculture , large-scale and low risk of contamination of product by mammalian pathogens or cancer- causing genes. However, genetically modified plants need the usage of bacterium. By the application of therapeutic agent of genetically modified organism human are able to cure many diseases. For example, many years people with insulin –dependent diabetes have controlled their disease by injecting insulin that obtain by pancreases of slaughtered animals. The main job of this hormone (insulin) is to uptake glucose from blood. Obtaining the insulin is very expensive process nd insulin from animal is not effective as human insulin.
Due to this reasons and the value of human insulin, producing of this hormone by the DNA recombinant techniques was an early goal the pharmaceutical industry. Another human hormone that is produced nowadays commercially by genetic modification of E. coli is somatostatin. Actually 500,000 sheep brains were needed to obtain 5mg of animal somatostatin. By contrast only 8 litters of a genetically modified bacterial culture are now neede to produce the same amount of the human hormone. Moreover, there are other therapeutic applications of (GMO) such as: subunit vaccine, DNA vaccines, and gene therapy. In process of gene therapy as result of (GMO), researchers are able to provide cures for some genetic diseases. By this ability defective and mutation gene are replaced by removing some cells in person and transforming these cells with normal gene. As a result, these cells must function normally in the person. For example gene therapy has been used to treat haemophilia B and severe combined immunodeficiency. There are several ways to insert modified genes into target cell’s organism.
GMO Controversies
The discussion about the economic, environmental and social effects of introduction and future application of GMO-based products has been a complex and controversial one. These include the effects on non-target organisms, insect resistance crops, gene flow and the loss of diversity as well as the issue on interfering with nature in which the modification process itself is disrupting the natural process of biological entities. There are many people at both sides of the arguments which have very strong feelings. One side of arguments are those who recognize the potential benefits of GMO technology on humankind. These benefits may include improving old tools or providing new ones, applying the new technology to allow human activities to be more favorable to ecosystem than occurs with traditional chemical technologies. They also feel that products and processes of genetic modification are generally safe and beneficial, and their use should be improved and encouraged. The underlying assumption of this view is that the scientific bases for genetic manipulation and other processes are well understood and can be well managed and controlled by the modern biotechnology industry. However, the other side believes that GMOs which are brought into the environment may have a chance of surviving and multiplying with undesirable consequences. They focus on the risks and unknowns about GMOs’ possible effects on ecosystems, species and human health.
The recent advances in life sciences create numerous bioethical problems requiring some   stringent regulation. As such, it is correctly argued that a guideline  on  “genethics”  must  be  formulated  in  order  to improve the scientists’, students’ and the citizens’ abilities to make judgment about what is morally wrong and right in this particular technology (Abu Bakar, 2002).
Ethical Issues
Bioethics addresses the impact of technology on individuals and societies. Bioethical issues include an individual's right to privacy, equality of access to care, and doctor-patient confidentiality. In the case of GMOs, a major bioethical issue is freedom of choice. Yet broader issues also arise, such as the ethics of interfering with nature, and effects of transgenic organisms on the environment.
Ethics in biotechnology includes the general subject of what should and should not be done in using genetically modification techniques in medical practice or in preparing pharmaceutical, food and agricultural products (Abu Bakar, 2002). The use of genetically modified organisms is a practice still in its early stages of development. But it has presented an exciting range of possibilities, from feeding the hungry to preventing and treating diseases; however, due to high complexity in ecosystems and unpredictability of environmental conditions, the scientists and publics expresses concern about the potential risk of using GMOs. So, some of the questions that need to be answered to build public acceptance and confidence are the following:
  • Are we destroying the lines between species by creating transgenic combinations?
  • What are the known health risks associated with GMOs?
  • What are the long-term effects on the environment when GMOs are released in the field?
  • What ethical, social, and legal controls or reviews should be placed on such research?
  • Are we inflicting pain and suffering on sentient creatures when we create certain types of genetically modified animals?
  • Will transgenic interventions in humans create physical or behavioral traits that may or may not be readily distinguished from what is usually perceived to be “human”?
  • If the blending of nonhuman animal and human DNA results in entities possessing degrees of intelligence or feelings never before seen in nonhuman animals, should these entities be given rights and special protections?
  • What unintended personal, social, and cultural consequences could result?
  • Will these interventions redefine what it means to be “normal”?
  • Who will have access to these technologies, and how will scarce resources be allocated?



Potential Effects of GMOs
The effects of GMOs can be classified into three main categories: scientific aspects, economic and political aspects and socio-cultural impacts. Each of these will be explained in more detail in following:
Effects on the Environment
1.      Herbicide Use and Resistance
Effects on the environment are a particular concern with regard to GMO crops and food production.  One area of development involves adding the ability to produce pesticides and resistance to specific herbicides.  These traits are helpful in food production, allowing farmers to use fewer chemicals, and to grow crops in less than ideal conditions.  However, herbicide use could be increased, which will have a larger negative effect on the surrounding environment.  Also unintended hybrid strains of weeds and other plants can develop resistance to these herbicides, thus neutralizing the potential benefit of the herbicide.    
2.      Effects on Untargeted Species
Although the pesticide can protect crops against unwanted insects, they can also have unintentional effects on neutral or even beneficial species.
Effects on Human Health
1.      Allergies
GMO crops could potentially have negative effects on human health as well.  When splicing genes between species, there are examples in which consumers have developed unexpected allergic reactions.
2.      Long-Term Effects
Because GMO technology has been available for such a short amount of time, there is relatively little research which has been conducted on the long-term effects on health.  The greatest danger lies not in the effects that we have studied, but in those which we cannot anticipate at this point.
3.      New Proteins
Proteins which have never been ingested before by humans are now part of the foods that people consume every day.  Their potential effects on the human body are as of yet unknown.
4.      Food Additives
GMOs also present us with possibilities of introducing additional nutrients into foods, as well as antibiotics and vaccines.  This availability of technology can provide nutrition and disease resistance to those countries that don’t have the means to provide these otherwise.  The distribution of these foods is more feasible than mass vaccination for current diseases.   However, even these possibilities carry with them potential negative effects such as the creation of antibiotic and vaccine-resistant strains of diseases.
Recent Bioethical Legislations
The recent legislation on GMOs regulates three main issues: authorization for placing GMOs on the market, labeling of products containing GMOs and traceability of these products.
1.      Authorization
The authorization procedure for the approval of genetically modigied products is intended to ensure that the safety of these products is scientifically established before they are allowed on the market.
2.      Labeling
Labeling rules are in place for all genetically modified products that have been authorized for marketing. It is important to note that the purpose of labeling is not to indicate that the products are unsafe, but only to provide consumers with the information necessary to know about the right to choose between GM and non-GM products.
3.      Traceability
This rule ensures that all products containing or consisting GMOs are required to be traceable at all stages of introducing into the market.
Conclusion and Recommendations
Transgenics and genetic engineering present intriguing and difficult challenges for 21st century scientists and ethicists. Until we as a society or, perhaps, as a global entity can agree on what beings, human or otherwise, are worthy of moral and legal status and respect, we can expect intense cross-disciplinary debate and discussion as new intelligent life is created through science and medicine.
Given the ethical issues mentioned above and the complexity of the technology used in creating GMOs, following recommendations can be proposed:
·         The governments can financially support independent research institutes to study the environmental and human health impacts of GMOs as well as to assess whether the product accomplishes its stated goal.  So the research labs will be responsible for investigating both positive and negative effects of the GMO in order to provide a safe and effective product to consumers.
·         All new GMOs can be subjected to strict testing and examination before they can receive FDA approval and be introduced to the market to ensure the safety and effectiveness of the product. 
·         All GMO products should be labeled properly. The public has the right to be informed about the nature of the foods they consume.  This is also essential for citizens with food allergies.  Further information about each GMO product could be available online or in information packets in grocery stores and restaurants. Distributors of the food may provide this information to the marketing location. 
·         Since education can enable consumers to make informed decisions regarding consumption of GMO products, the governments can financially support public education regarding GMO products. In addition, it is beneficial if the governments fund the distribution of informative posters to cooperating grocers. A Government-operated database is very useful to be available online for easy public access to information regarding GMO technology and specific GMO products.


References
Prevost D., Calster, G. V., The EU Legislation Regarding GMOs and its Implications for Trade, in Challenges and risks of genetically engineered organisms, Organization for Economic Co-operation and Development, USA, 2004
Stemke, D. J., Genetically Modified Microorganisms: Biosafety and Ethical Issues, in The GMO Handbook for genetically modified animals, microbes, and plants in biotechnology, Parekh, S. R., Humana Press, New Jersey, 2004
T. W. Bates, A. M. Blair, E. S. Jermé, A. B. Keller, G. E. Lavik, K. A. McMaken, Executive Summary from the Genetically Modified Organism Exploratory Committee, Online at <http://www.macalester.edu/~montgomery/gmos2.htm>, Accessed on 15 October 2011.
Z. Hamin,  S. A. Idris, Bioethical Issues on Genetically Modified Organisms (GMOs) In Malaysia: Biting Into the Legal Protection under the Biosafety Act 2007, 2nd International Conference on Biotechnology and Food Science, IACSIT Press, Singapore, 2011

Health and Safety Executive, About Genetically Modified Organisms, [Online] Available from: <http:// http://www.hse.gov.uk/biosafety/gmo/about.htm>, Accessed: 12th October 2011

Tortoa, Funke, Case, An Introduction to Microbiology, Tenth edition, pp 212-214, 253-264,

Stem Cells - Final Assignment

Stem Cells
Stem cells are in detail biological cells found in all multicellular organisms. This cells can divide  through mitosis and differentiate into various specialized cell types. It can also self-manipulate to produce more stem cells on the specific site. In mammals, there are two broad types of stem cells: adult stem cells, which are found in various tissues and embryonic stem cells which are isolated from the inner cell mass of blastocysts. In matured organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues and rejuvenating it. In a developing embryo, stem cells can differentiate into all the specialized cells (these are called pluripotent cells), but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.
Stem cells can now be artificially grown and transformed into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves through the process of cell culture. Adult stem cells which contains high plastic cells are routinely used in medical therapies and recoveries. Stem cells can be taken from a variety of sources, for instance umbilical cord blood and bone marrow.  Future therapies by promising candidates have proposed that embryonic cell lines and autologous embryonic stem cells may be generated through therapeutic cloning. Research into stem cells grew out of findings by Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s.(wikepedia)
There are three sources of autologous adult stem cells:
1) Bone marrow, which requires withdrawal by harvesting, that is, drilling into bone (typically the femur or illiac crest),
 2) Adipose tissue (lipid cells), which requires removal by liposuction, and
3) Blood, which requires extraction through pheresis, wherein blood is drawn from the donor, (similar to a blood donation) passed through a machine that extracts the stem cells and proceeds other portions of the blood to the donor.
Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may stock his or her own blood for possible surgical procedures.
In other words, stem cells have the remarkable potential to develop into many different cell types in the body during premature life and growth. In many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.
Stem cells are notable from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.
Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitrofertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. This new type of stem cell, called induced pluripotent stem cells (iPSCs), will be discussed in a later section of this document.
Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.
Laboratory studies of stem cells enable scientists to learn about the cells’ essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.
Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms.

Treatment
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 near future, medical researchers predict being able to use technologies derived from stem cell research to treat a wider variety of diseases including cancerParkinson's diseasespinal cord injuries, sclerosis, multiple, 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.
            One concern of treatment is the risk that transplanted stem cells could form tumors and become cancerous if cell division continues uncontrollably. Stem cells are widely studied, for their potential therapeutic use and for their inherent interest.
Supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It has been proposed that surplus embryos created for in vitro fertilization could be donated with consent and used for the research.

 

 

Research Ethics and Stem Cells
            Stem cells show potential for many different areas of health and medical research, and studying them can help us understand how they transform into the dazzling array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are caused by problems that occur somewhere in this process. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.
Research on one kind of stem cell—human embryonic stem cells—has generated much interest and public debate. Pluripotent stem cells (cells that can develop into many different cell types of the body) are isolated from human embryos that are a few days old. Pluripotent stem cell lines have also been developed from fetal tissue (older than 8 weeks of development).
As science and technology continue to advance, so do ethical viewpoints surrounding these developments. It is important to educate and explore the issues, scientifically and ethically.
         Respect for the person (Autonomy)
Respect here refers to the value of human life. Since through embryonic cultivation, clone species of the fetuses can be formed. Religious views contradict with this standard as we should not be God’. We should not mess around with human life as it is God’s will to deal with it. Scientific explanation differs from this belief thoroughly claiming that whatever benefits mankind gains in the name of science is adequate not taking the adverse effects into considerations.

         Beneficence (Do Good)
            Since stem cells have the ability to differentiate into any type of cell, they offer something in the development of medical treatments for a wide range of conditions. Treatments that have been proposed include treatment for physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). However further treatments using stem cells could potentially be developed due to their ability in repairing extensive tissue damage.
Great levels of success and potential have been shown from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. Embryonic stem cells can become all cell types of the body which is called pluripotent. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. Nevertheless, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become. In addition, embryonic stem cells are considered more useful for nervous system therapies, because researchers have struggled to identify and isolate neural progenitors from adult tissues since it’s very minute in size or structure.

         Nonmaleficence (Do No Harm)
The stem cell controversy is the ethical debate centered only with research involving the creation, usage, and destruction of human embryos drastically. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves the creation, usage and destruction of human embryos. For example, adult stem cells, amniotic stem cells and induced pluripotent stem cells do not involve creating, using or destroying human embryos and thus are minimally, if at all, controversial. In other words stem cells do not cause harm as it caters more benefits compared to damage.

         Justice (Fairness)
Justice here again refers to the question of whether will there be equal treatment of true virtue of those cloned beings. It is indeed an argumentative topic in the sense of ethics and right codes of conduct. Ethical desiderata include: equitable access, maximized potential therapeutic benefit across demographic and disease groups, and reasonable cost. Other ethical priorities include the minimization of stem cell line and tissue wastage, risk of immune rejection, risk of transmitting diseases, the use of human embryos, and risk to those contributing source cells. The therapeutic potential of stem cells for treating and possibly curing many serious diseases constitutes a major justification for large-scale investments of public and private resources in human stem cell research. To justify doing so, however, requires some guarantee that people in need will have access to the therapies as they become available. Principles of justice are based on treating persons with fairness and equity and distributing the benefits and burdens of health care as fairly as possible in society. This would require equitable access to the benefits of stem cell research, without regard to the ability to pay.

 

 STEM CELL RESEARCH - ARGUMENTS REGARDING THE USAGE OF THE KNOWLEDGE

The following arguments are not exclusively in use when talking about stem cell research.
Pros
Stem cell research can potentially help treat a list of medical problems. It could lead humanity closer to better treatment and possibly cure a number of diseases:
  • Parkinson’s Disease
  • Alzheimer’s Disease
  • Heart Diseases, Stroke and Diabetes (Type 1)
  • Birth Defects
  • Spinal Cord Injuries
  • Replace or Repair Damaged Organs
  • Reduced Risk of Transplantation (You could possibly get a copy of your own heart in a heart-transplantation in the future
  • Stem cells may play a major role in cancer
Better treatment of these diseases could also give significant social benefits for individuals and economic gains for society in whole.


Cons
  • Some argue that stem cell research in the far future can lead to knowledge on how to clone humans. It is hard to say whether this is true, but we have seen devastating consequences of other research-programs, even with good intentions, such as nuclear research which could cause massive massacre.
  • "Humans should not be trying to play God"





CONCLUSION
The stem cell-research is an example of the, sometimes difficult, cost-benefit analysis in ethics which scientists need to do. Even though many issues regarding the ethics of stem cell research have now been solved, it serves still as a priceless example of ethical cost-benefit analysis.
The advancement of science has transformed our lives in ways that would have been unpredictable just like 50years ago. Whether stem cell research will have a similar effect remains to be determined, but the promise is so great that it seems wise to consider seriously how best to further such research in a manner that is sensitive to community sensibilities. Open conversations about research and use of human stem cells are well underway. If humankind were to take stem cells to a higher understanding, extracting only the beneficial outcomes it will surely improve our  living standards.


Reference
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2.      Tuch BE (2006). "Stem cells—a clinical update".Australian Family Physician 35 (9): 719–21.PMID 16969445.
3.     Becker AJ, McCulloch EA, Till JE (1963). "Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells". Nature197 (4866): 452–4. doi:10.1038/197452a0.
4.      Hans R. Schöler (2007). "The Potential of Stem Cells: An Inventory". In Nikolaus Knoepffler, Dagmar Schipanski, and Stefan Lorenz Sorgner.Humanbiotechnology as Social Challenge. Ashgate Publishing, Ltd. p. 28. ISBN 0754657558.
5.     Mitalipov S, Wolf D (2009). "Totipotency, pluripotency and nuclear reprogramming". Adv. Biochem. Eng. Biotechnol. 114: 185–99. doi:10.1007/10_2008_45
6.      Friedenstein AJ, Gorskaja JF, Kulagina NN (1976). "Fibroblast precursors in normal and irradiated mouse hematopoietic organs". Experimental Hematology 4 (5): 267–74. PMID 976387.
7.      Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M (2010-02-25). "Direct conversion of fibroblasts to functional neurons by defined factors".Nature 463 (7284): 1035–41.doi:10.1038/nature08797. PMC 2829121.
8.     Wu DC, Boyd AS, Wood KJ (2007). "Embryonic stem cell transplantation: potential applicability in cell replacement therapy and regenerative medicine". Front Biosci 12 (8–12): 4525–35. doi:10.2741/2407.
9.     Ariff Bongso; Eng Hin Lee (2005). "Stem cells: their definition, classification and sources". In Ariff Bongso; Eng Hin Lee. Stem Cells: From Benchtop to Bedside. World Scientific. pp. 5. ISBN 981-256-126-9.
10.   Jiang Y, Jahagirdar BN, Reinhardt RL, et al. (2002). "Pluripotency of mesenchymal stem cells derived from adult marrow". Nature 418 (6893): (41–9).