INTRODUCTION: Stem cells are cells which are found in almost all multicellular organisms. Stem cells was proposed by a histologist Maksimov. A in 1908. They develop into many different types of cells in the body during their early life and growth and serve as a internal repair system in many tissues. Formation of new cells can be seen when stem cells division starts these new cells can either form a stem cell or other types of cells like muscle cells,brain and red blood cells with specialized functions. Stem cells are the objects in biomedical research and are differentiated from other types of cells by two main characteristics. Firstly, Stem cells are the undifferentiated cell types they possess the capacity of both self renewable during cell division. Secondly, Potency which means they can be differntiated into differnt types of specialized cells with specific function.(Bishop et.al., 2002). Stem cells can be totipotent and pluripotent. In some organs like gut or bone marrow the stem cells divide either to replace or repair the damaged or worn out tissues while in other organ system like pancreas they divide under some specific function Totipotent stem cells can give rise to a functional organism as well as to every cell type of the body. Pluripotent stem cells are capable of giving rise to any tissue type, but not to a functioning organism. Multipotent stem cells are more differentiated
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and thus can give rise only to a few tissue types. For example, a specific type of multipotent stem cell called a mesenchymal stem cell can produce bone, muscle, cartilage, fat, and other connective tissues. (Pittenger et.al., 1999). They are two types of Stem cells 1) Embryonic stem cells 2) Adult stem cells also known as somatic cell or tissue specific. Embryonic stem cells are derived from the blastocysts and are pluripotent instead of totipotent because they do not have the ability to become part of the extra-embryonic membranes or the placenta while the adult cells are present in adult tissues while the stem cells found in developed tissues are the Adult stem cells and the example for this is the hematopoietic stem cells of blood which cannot give rise to the cells of a different tissue, such as nerve cells in the brain (Frankel et.al.,1999). The difference between between embryonic and adult stem cells(somatic) is their origin that is embryonic cells can differntiate into any cell types but adult stem cells are limited and can differentiate into the cells of their own tissue by this the grown cells wont be rejected by the immune system during treatment and these cells also differ by mutation frequency (James et.al.,2002). The stem cells derived from the human embryo is known as Human embryonic stem cells and these cells are for reproductive purpose. While, in 2006 researchers have observed new type of specialized adult cells this cells are called as Induced pluripotent cells (iPSCs). Parthenogenetic stem cells are also one type of stem cells derived from activated human oocytes USES: Stem cells are useful in treating diseases like diabetis and heart diseases and many works are being done on how to use stem cells for cell based therapies in treating diseases which is also called as regenerative medicine. Stem cells have the ability to replace the damaged cells and can be used in treating heart failures. spinal injuries and parkinson’s diseases for example, neural stem cells are able tp regenerate nerve tissue damaged by spinal injury. Stem cells are useful in screening toxins in substances such as pesticides and also used during development of new methods for gene therapy that may help those who are suffering from genetic illiness. They are also used in pharmaceutical industry for testing the new drugs before testing on animal and humans. Induced pluripotent cells are the adult stem cells have been genetically remodelled to an embryonic stem like to express genes and factors which maintains the properties of embryonic stem cells.
EMBRYONIC AND INDUCED PLURIPOTENT STEM CELLS:
Embryonic stem cells are from the earliest stages of human embryo that develop into eggs by invitro fertilization while other embryos are developed for research and extracted after five days growth. It is known that embryonic stem cells divide indefinitely so only a single embryo can form lines of cells to use for treatment.(Thomson et.al.,1998) These cells are undifferentiated but has a ability to differentiate into any cell, tissue or organ in the body. These stem cells can also become nerve, muscle cells or any other type of human cells. The process involved in formation of ES cells is the ovaries are removed and after 76hours of copulation they are treated with media containing serum overnight.The following day the inner cell mass of embryos are removed and cultured on fibroblast after few weeks colonies grew which showed pluripotent characters referred to as ES cells. Embryonic stem cells are used to treat a host of diseases, such as Parkinson’s disease, spinal cord injury, and diabetes (Martins.,1981). For research, these embryos are destroyed in the process of deriving embryonic stem cells. ES cells have got a great potential for long term therapies but the issue arises regarding safety. Transplanted ES cells have uncontrolled growth and could generate tumours which is seen in laboratory cultures by scientists and there are not sure how they behave inside the body. So, this is to be studied before proceeded in clinical trials while another issue is tissues derived from the ES cells are rejected by patient’s immune system after transplantation. To overcome this issue tissue rejection currently, drugs can be used which suppresses the immune system but these drugs can be infectious thus drugs without any side effects are being investigated by the researchers or alternatively adult stem cells can be used. The major issue is in process of extracting the embryonic cells the embryos have to be destroyed this is opposed by many people and raises ethical issues. Alternatives are being investigating by combining the stem cell technology with cloning by a method called (SCNT) somatic cell nuclear transfer.(Stewart et.al.,2007). It is a method which involves insertion of the nuclei of the somatic cell into the oocyte which develops into the embryo. This embryo derives the embryonic stem cell lines which is carried out in several mammalian species but till date No ES cells have been successfully developed by this method and also requires destruction of many embryos compared to other methods. And the other issue by usig this method is therauptic human cloning would lead to reproductive human cloning which leads to maral and social danger. The use of ES cells got many ethical issues as it is derived by destroying the embryos which raises fundamental concers of human life. (Tabar et.al.,2001).
Problems associated with stem cell research according to the researchers embryonic stem cells are known for the cell baesd therapies as they are more versatile than adult stem cells but the same properties of these cells make them unusual for therapy as these will migrate all over the body and produce tumours. Growing and maintaining embryonic cell lines prove that they are problematic by performing experiments in mice as some of these get mutated and unusable to the patients. To overcome this problem adult stem cells acan be used to eliminate mutation tissue incompatibility. The pharmaceutical companies could not puruse these therapies due to financial incentives ( Phimister and drazen,2004).
Recent advances in stem cells have new applications possible for stem cell based technology. It is now possible to reprogram differentiated human somatic cells into pluripotent cells that are functionally equivalent to embryonic stem cells. In 2006, specialized adult cells are been reprogrammed genetically to assume a stem cell like state called as “Induced pluripotent stem cells”. (Fenno.et.al., 2008). The use of ES cells as an alternative to oocytes which can be reprogrammed as an Human somatic cells. This can be done by fusion of human embryonic stem cells with fibroblasts which results hybrid cells.(Cowan et.al.,2005). These cells exhibits morphology and growth proper of embryonic stem cells and also express their genes. Transplantation of induced pluripotent cells into mice resulted in tumour containing variety of tissues on injection into the blastocyst showed mouse embryonic development This shows that Induced Pluripotent stem cells can be produced from fibroblast on addition with defined factors like oct3/4,Sox2 and klf4(Takahashi and Yamanaka.,2006).
Researchers have demonstrated a novel technique for production of IPS cells by transforming Adult Skin cells which is considered as a fast reliable and safe method, viruses were used to insert the specific genes into the adult cell would result in increased potential for adverse outcomes and also increases the chance of genetic defects thus it would affect the patient treating with stem cell therapy.(Soldner et.al.,2009) Thus, alternatively transgenes or reprogramming proteins can used for insertion to overcome the risk and after induction using protein factors or virus free factors that can be removed to induce pluripotency which develops into IPS cells that does not have any risk.(Kaji et.al.,2009) As, IPS cells also raises ethical problems related to germline alterations. However using virus free factors can overcome the problem of germline alteration.
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In 2010, researchers have used Induced pluripotent stem cells to treat rodents suffering with parkinsons disease and this research was successfull this is done by transplanting the induced pluripotent cell neuron into the rodents mid brain injury which is similar to Parkinsons disease in humans by this the cells became functional and showed improvement. Thus induced pluripotent cells may be useful for future disease models and cell-based therapies.
Induced pluripotent stem cells offer immense potential for regenerative medicine and studies of development and diseases. Thus analysis of genomic transcriptional activity, gene activation, allele specific gene expression and DNA methylation shows that the somatic cell was reprogrammed to an embryonic state which provides a system for investigating the mechanisms. To Induce pluripotent somatic properties which are similar to ES cells properties is done by introducing active genes or derivatives of RNA or protein products into the somatic cell but this process of acquiring pluripotency is not genetically but involves Epigenomic Reprogramming. There are differences between ES and IPSC cells regarding chromatin structure and gene expressionby showing few similarities while the other reports show that there is epigenetic differences and alteration. Reprogramming of a somatic cell into pluripotent state requires complete change of Somatic cell to an ES cell like state but this is not reported yet. On performing genomic profiling of the DNA methylomes of both ES and Induced pluripotent cells similarities are seen but every single line shows different reprogramming variability compared to both ES cells and other Induced pluripotent stem cells. Patterns of DNA methylation are seen as epigenetic change at the tips and centromeres of the chromososmes and show differences in CG methylation and histone modifications. Thus, Induced pluripotent cells may not be suitable substitute for embryonic cells. (Lister et.al., 2011).
Human embryonic stem (ES) cell research has been the best way for the cell-based therapies for a number of diseases but the issue raises with destroying the embryos to produce these cells. The use of IPS cells has less ethically problematic than the use of Embryonic cells as production Of IPS cells does not require destroying the embryos. But the use of induced pluripotent cells raises ethical concerns to somatic cell reprogramming as there is a difference seen between the ES and Ips cells and the debate over stem cell therapy is increasingly becoming irrelevant but ethical issues regarding the Embryonic stem cells would not entirely go away.So, the study of all the types of stem cells should be done as it is not known which is useful for the cell replacement therapticus.
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