Prospects and Ethical Concerns of Embryonic Stem Cells Research-a Review

Stem cell research has appeared as a silver lining of hope over the dark cloud of some untreatable diseases like cancer and certain neurological disorders. Embryonic stem cells, the tabula rasa, holds much promise in this regard owing to its totipotency, howbeit, it has whirled a severe tempest all over the world on the point of humanity. The present review article includes the chronology of stem cell research with special reference to the techniques that were evolved in due course of research, the controversy over the application of embryonic stem cells for therapeutics and present status of stem cell research under Indian context. India is being increasingly alluring the foreign companies to invest in this project since a huge prospect in stem cell marketing business is foreseen in this country.


Introduction
in culture, while adult stem cells are rare in mature tissues and methods for expanding their numbers in Stem cell research that has emerged as one of the cell culture are yet to be worked out (Cezar, 2007).The most intriguing hierarchy of biological science is third kind of stem cells i.e. the induced pluripotent moving at a dazzling pace with an aim to address stem cells (iPSC) are specially treated ordinary cells certain questions of medical problems (viz.organ (viz.skin cells) induced to exhibit some of the transplantation, cancer research etc).Stem cells which properties of embryonic stem cells.This branch of are fundamentally of three types, viz., adult, stem cell research is at puerile stage, howbeit, it seems embryonic and induced pluripotent stem cells, can be to offer the advantages of embryonic stem cells induced to transform into specialized cells under without any ethical and rejection problems (Colman, certain physiological and experimental conditions. 2008, Ellis et al., 2009).The present review The adult stem cells (ASC) are harbored in the adult tissues with the primary roles of maintenance and encompasses the bases of embryonic stem cell research; its potential applications vis-à-vis associated repair and have limited number of possible pathways to differentiate into cell types.Whereas the embryonic ethical concerns.stem cells (ESC), derived from the inner cell mass A Retrospect down the Time Line of Stem Cell (ICM) of preimplantation embryos (Evans and Research Kaufman, 1981), embryonic germ cells and fetal germ The beginning of stem cell research dates back to cells (Matsui et al., 1992, Resnick et al., 1992) , can th the mid 19 century with the discovery that some cells differentiate into many cell types.While the adult stem can procreate other cell types (Cooper, 2004).In the cells are only multipotent, ESC comes under the th category of either being totipotent or pluripotent early 20 century true stem cells were identified as depending on the stage of harvesting the stem cells.
progenitor of blood cells which led to administration Embryonic stem cells popularly called as 'tabula of bone marrow through oral route to the anemic rasa' as they typically exhibit little or no patients.Some sporadic research work in bone differentiation and are considered to possess more marrow transplantation in mice ultimately bid fair for therapeutic potential than adult stem cells (Rossant allogenic transplantation in human being (Harris, and Nagy, 1999).By virtue of this property, ESC can 2009).A revolutionary discovery in immunogenetics form all the 220 types of cell found in the human body by Jean Dausset (1958) unveiled that the histo-(including germ cells) (Placzek et al., 2009).A large compatibility antigens (Dausset et al., 1970), which numbers of embryonic stem cells can be easily grown enable our immune system to discern the self and non-In Search of Suitable Markers for Embryonic self proteins, are the key to the graft rejection in human Stem Cells being and animals.Initially physicians performed bone marrow transplant between identical twins only.
The embryonic stem cells have two important The first successful bone marrow transplantation traits; the smallest amount of cytoplasm and fastest between unrelated individual was performed in 1973 proliferation in the given population.In addition to the (Dupont, 1997).This marked the beginning of era of distinctive morphological features some additional organ transplantation in human being, which also markers of undifferentiated pluripotent cells also need broached up some controversy over the validity of this to be investigated to confirm the authenticity of stem technique from the viewpoint of mankind.In 1984, US cell cultures.Alkaline phosphatase was used for the Congress passed the National Organ Transplant Act to first time as a biochemical marker for bovine ESC establish a national bone marrow donor registry vis-à- (Kitiyanant et al., 2000).The embryonic stem cells are vis to probe the graft acceptability (Verklan, 1993).known to express a high specific activity of alkaline The stem cell research started propelling at leaps and phosphatase which declines during progressive bounce thereafter.The first embryonic cell lines were differentiation resulting in low ALP activities in developed from the inner cell mass by James somatic differentiated cells (Mueller and Tuan, 2008).Thompson (1998) at the University of Wisconsin -Alkaline phosphatase activity has been detected in Madison (Thomson et al., 1998).

Isolation of Inner Cell Mass -the Source of Pluripotent Embryonic Stem Cells
SSEA-1, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81 antigens was detected by immunocytochemistry with Isolation of the inner cell mass (ICM) is a crucial specific primary antibodies in primate ESC line step while culturing embryonic stem cells (ESC).The (Thomson et al., 1995).Besides several genomic first ever reported method to derive large quantities of markers namely, Oct4, Nanog, Stellar, and GDF3 have pure ICM from the mouse blastocyst was by been identified as ESC marker-genes (Tay et al., 2008, immunosurgical technique (Solter and Knowles, Chiou et al., 2008).Researchers are presently charac-1975) wherein the trophoblastic cells were stamped terizing the up-and down-regulation of such marker out by exposing them to rabbit antimouse serum genes and their association with fatal diseases like followed by guinea pig complement-dependent cancer (Riekstina et al., 2009, Busch et al., 2008).antibody cytotoxicity.The immunosurgical isolation of ICM was successfully used in several species, like, Thrust Areas for Application of Embryonic Stem Cells mouse, rhesus monkey, swine and human embryos etc (Thomson et al., 1995, 1998, Wianny et al., 1997).In ESC has tremendous application in varied fields, later years the immunosurgical isolation of ICM has including human welfare and veterinary science.gradually been replaced by some modified techniques Totipotent ESC provide a powerful tool for the studies due to its underlying problems like; it is labor intensive of early embryonic development (Wiles and and involves possible risk of contamination.In a Johansson, 1997, Rathjen et al., 1999), gene targeting different technique, cultured mouse blastocysts were (Lohnes, 1999) synthetic eggs obtained from culturing stem cells can be stripped of their own genetic material and used as a destruction of blastocysts formed from laboratoryfertilized human eggs.For those who believe that life recipient for nuclei from desired adult somatic cell.After reprogramming they can develop to blastocyst begins at conception, the blastocyst is a human life and stage and used to derive new ES cells.These cells in to destroy it is unacceptable and immoral (Robertson, turn could be prompted to produce specific cell types 2001).Against this, embryonic research advocates for transplantation, to treat specific diseased argue that the tiny blastocyst has no human features conditions.Also these synthetic eggs can be used to (Romeo-Casabona, 2008).This seems to be the only obtain diseased tissues (by taking the nucleus from controversial issue standing in the way of stem cell adult diseased tissue).Such ES cells would provide an research in North America.Others argue against such unlimited source of diseased tissue allowing a better research on medical grounds.Mice treated for opportunity to study the disease in a better way.The Parkinson's with embryonic stem cells have died from study on stem cells also provides an opportunity to brain tumors in as much as 20% of cases (Basu, 2006).study the stem cell niche.The ability to grow pure Embryonic stem cells stored over time have been populations of specific cell types offers a proving shown to create the type of chromosomal anomalies ground for chemical compounds that may have that create cancer cells (Cowan et al., 2004).Looking medical importance (Deng, 2010).
at it from a more pragmatic standpoint, funds devoted Treating the specific cell types with chemicals to embryonic stem cell research are funds being taken and measuring their response offers a short cut to sort away from the other two more promising and less out chemicals that can be used to treat the diseases that controversial types of stem cell research mentioned involve those specific cell types.Stem cell technology, above.Currently, American federal funding can only therefore, would permit the rapid screening of go to research on stem cells from existing (already hundreds of thousands of chemicals that must now be destroyed) embryos.Similarly, in Canada, as of 2002, tested through much more time-consuming processes.scientists are not allowed to create or clone embryos Screening drugs by testing them on cultured for research and can only use those embryos that are embryonic stem cells could help reduce the risk of discarded by couples voluntarily (Baylis and Herder, drug-related birth defects (http://www.guardian.co.2009).uk/science/2007/oct/03/stemcells.animalrights).This

A Tug of War between Science and Conscience
could find an application in animal breeding, in overcoming germ cell tumors, in examining many These ethical concerns over human embryonic complex processes including the roles of key genes stem cell research were sought as early as in 1973, and mechanisms underlying uniparental gene when an abeyance was placed on government funding expression.The use of ESC technology in livestock for human embryo research.Thereafter, various may also overcome current limitation on efficient gene turbulence over this issue was observed in USA senate transfer by providing an abundance of totipotent stem and also among the rank and file, both in for and cells to be genetically manipulated by using against the use of human embryonic stem cells.In conventional recombinant techniques.As far as 2000, President Bill Clinton allowed funding of reproduction is concerned, obtaining germ cells from research on cells derived from aborted human fetuses, but not from embryonic cell.On August 9, 2001, stem cells is exciting as well as helpful for treatment of President George W. Bush gave consent for Federal infertility.The cultured germ cells may be used for cell-based therapies for reproductive disorders (Du funding of research only on existing human embryonic stem cell lines created prior to his announcement and Taylor, 2009, Moore et al., 2008).(Anonymous, 2006).The elective victory over the

Ethical Concerns
issue of stem cell research funding organization When we consider stem cell ethics, we initiative led to the establishment of "California immediately find we are balancing what medical good Institute of Regenerative Medicine" in 2004 (Hall, might come from using embryonic stem-cell lines 2007).In the summer of 2006, President Bush stood against the possible harm, not only to an embryo, but his ground on the issue of stem cell research and to a society that already may place too little value on vetoed a bill passed by the Senate that would have human life.Stem cell research has become expanded federal funding of embryonic stem cell controversial because it focuses attention on moral research.Many American scientists were putting pressure on the government to allow ESC research and and theological issues as well as medical ones.Use of embryonic stem cells for research involves the compete with the European counterpart involved in embryonic stem cell cloning.Very recently, present drawn the attention of the scientific community and President of USA, Barack Obama modified the visionary personages of India.The government has existing norm to use embryonic stem cells for research constituted cogent guidelines for installing a robust purpose as to use the embryonic cells that are disposed regulatory regime and a monitoring agency to off from fertility clinics saying these words, "As a augment competent stem cell research, due to the person of faith, I believe we are called to be for each growing private and public healthcare centers, that other and work to ease human suffering.I believe we claims stem cell treatment for a number of diseases.have been given the capacity and will to pursue this The department of biotechnology (DBT-GOI) and research….. and the humanity and conscience to do so Indian Council of Medical Research (ICMR) in light responsibly"(http://www.reuters.com/article of the above mandate published the guidelines for /idUSN0946466020090309).The restriction on stem cell research and therapy in November 2007, funding to the stem cell research project imposed by addressing the ethical, scientific, legal and policy President G. Bush in 2001 was lifted by present issues (Director General, ICMR.2007).
th India has commendable prospects in this arena in President Obama on 9 March, 2009 and simultaneously the coming years.Keeping in view its potential assuring to craft strict guidelines for the same (Hutson, therapeutic applications, both basic and translational 2009, http://news.bbc.co.uk/2/hi/americas/ 7929690.stm).Very surprisingly, shares of the stem research are being promoted by the ICMR in various cell research company escalated upto 73% on the news.
institutions, hospitals and the industry.Till date, more than 55 programmes have been identified and Out of necessity, use of stem cell lines from alternative non-embryonic sources (viz.bone marrow, supported on various aspects of stem cell research like, Umbilical-cord-derived stem cells) has received more generation of human embryonic stem cell lines, attention in recent years and has already been differentiation of pancreatic progenitor cells to insulin demonstrated as a successful option for treatment of secreting cells, isolation of multi potential adult certain diseases and, with sufficient funding, other progenitor cells from bone marrow and their clonal solutions might be found that are acceptable to expansion, etc (http://india.gov.in/sectors/science/everyone.Another option is use of uniparental stem stem_cell__biology.php).Most of the renowned cells.Although these cells lines have some medical research institutes have come up to offer their disadvantages or shortcomings compared to finest in this domain.The All India Institute of Medical embryonic cell lines (they are shorter-lived), there is Sciences (AIIMS), New Delhi, had pioneered the vast potential if enough money is invested in treatment of heart problems using stem cells in India.researching them further, and they are not technically The department of biotechnology (DBT-GOI), has considered individual living beings by pro-life commenced a mission on national stem cell research advocates.Biotech companies such as Revivicor and programme on "human embryonic stem cell" in ACT are researching techniques for cellular collaboration with Indian Council of Medical reprogramming of adult cells, use of amnionic fluid, or Research (ICMR), in six cities across India (New stem cell extraction techniques that do not damage the Delhi, Bangalore, Pune, Mumbai, Hyderabad and embryo, that also provide alternatives for obtaining Vellore) in the year 2004 (http://www.financialviable stem cell lines.On the contrary, one cannot express.com/news/dbt-icmr-initiate-stem-celloverlook the returns provided by the embryonic stem research-programme/101293/).cells, like their potentiality to make any variety of The Armed Forces Medical College, Pune, has cells, immortality and readily available aspect (i.e.embarked on stem cell therapy for the first time, with embryos from in-vitro fertilization clinics).Since, an aim to regenerate the dead cardiac muscles new stem cell lines already exist due to the common following a heart attack.The Cardio Thoracic Centre practice of in vitro fertilization, advocates of at Military Hospital has already initiated the stem cell embryonic stem cell research uphold their claim that therapy on two patients with acute myocardial new human lives will not be created for the sole infraction, by injecting stem cells into the artery purpose of experimentation and thus embryonic stem leading to the diseased organ (Chakraborty et al., cell continues to be the primary choice for the 2009).The central government has sanctioned Rs 30 researchers (Baylis and Krahn, 2009).crore to the Christian Medical College, Vellore, to

Stem Cell Research in India
undertake a research project on stem cells.Apollo Hospitals Group has announced on 21st March' 2009, The controversies that sprung up from the disputation its plans to establish a Rs.600 million project stem cell over the hype and hope of stem cell therapy has also , chimera formation (Qin et al., 2008), differentiated into giant trophoblastic cells and large cloning (Stice and Keefer, 1993, Modlinski et al., egg-cylinder like structures.The later were sub-1996), transgenic animal production (Robl et al., cultured to yield proliferating colonies of cells 2007), gene therapy (Uzzaman et al., 2005) and resembling ESC.This technique was further improved regenerative medicine vis-à-vis drug designing by placing the ICM on feeder layer (Wobus et al., (Brustle et al., 1997).Because of their potential use for 1984) to provide a coating of non-dividing cells that targeted gene manipulation, isolation of ESC could furnish a sticky surface to the inner cell mass and have enormous potential not only for treating certain secretes a host of growth factors such as leukemia human diseases like Alzheimer's disease, diabetes, inhibitory factor (LIF) (Smith et al., 1988; Kakegawa cancer, stroke, etc in human being, but various et al., 2008).Subsequently a three step technique was agricultural, biomedical and pharmaceutical devised to generate ESC like cell lines by trypsinizing applications also.Thorough understanding of the factors contributing to the establishment of ESC in the disaggregated rabbit blastocyst and plating onto vertebrate species, including human being would help murine and porcine embryonic fibroblast (MEF) feeder layer (Niemann and Strelchenko, 1994, Kim et treating certain diseases (Stice et al., 1996).The al., 2007).