- Ethics in relation to use of iPS or EC stem cells for doctors
The U.S. government will now be able to fund research that involves human embryonic stem cell lines derived since August 9, 2001,as president USA Mr BarraK Obama’s remarks. Pluri -potent stem cells includes*embryonic stem (ES) and germ (EG) cell lines and embryonic carcinoma (EC) cell lines ES cells, isolated from human blastocyst and maintained in culture without differentiation for long periods.EG cells are isolated from primordial germ cells of genital ridges of 5-9 weeks old fetuses and form embryoid bodies***. EC cells are isolated from tetarocarcinomas.The use of induced pluripotent embryonic stem cells (iPS) for regenerative medicine has captured the public’s imagination and fuelled rising expectations of clinical benefits in very advanced countries. Clinicians in advanced countries today increasingly needs to manage his patients’ expectations of what exogenious stem cells may, or indeed may not, offer. Regenerative medicine is however a long way discipline. It can be summarized as treatments that seek to restore structure and function after injury and, by this definition, includes solid organ transplantation by exogenious stem cells from stem cell banks. Exogenious cultured Stem cells are also routinely today used in hematology( Peripheral blood stem cells/ cord blood stem cells/ allogenic bone marrow stem cells are used for hematological malignancies even in west Bengal, India), plastic surgery (cultured autologous keratinocytes for skin loss or burns), and in orthopedics (autologous chondrocyte transplantation for articular cartilage defects) or in CNS disorders like in Parkinson’s diseases, Multiple sclerosis, Motor neurone disease as Neurons can be generated from skin, skeletal muscle, hematopoietic stem cells (HSC), mesenchymal stem cell lines etc.. But surprisingly not for stroke which is a major burden of neurological mortality. The use of such human embryonic stem cells both for research and therapeutic purposes sparks an ethical debate in our mind, Induced pluripotent stem cells (iPS) are mature cells taken from adults, such as skin cells, and transformed in the laboratory into pluripotent cells that can mature into a variety of different cell types. Researchers have generated more than 10 disease-specific iPS cell lines derived from patients with a variety of genetic diseases, such as diabetes and Parkinson’s disease but not for stroke. Please note it that exogenous stem cell transplantation, is fraught with both technical ,ethical and huge but huge cost difficulties for resource poor counties. A more attractive option that authors think it will be much effective if one can however some how would mobilize endogenous progenitor cells instead of exogenous cultured stem cell therapy. Many colony stimulating factors such as erythropoietin (EPO) and granulocyte colony stimulating factor (G-CSF) are used to mobilize the hematopoitic stem cells as for example2.Because iPS cells are derived from adult tissue, they seemingly sidestep the ethical issues of working with human embryos. A 2005 report by the President’s Council on Bioethics called iPS cells “ethically unproblematic and acceptable for use in humans.” A recent paper argues that the potential uses of iPS cells might pose ethical issues to the donors. iPS cells could be used to identify and test new therapeutics at research level and might also themselves be used as part of cell replacement therapy. Because the technology is so new, there are many unknown applications, adverse reactions – which is fine, because it looks like iPS cells can be grown in the laboratory indefinitely. Hence the ethical issue: People who donate their cells for iPS research might not have intended that their cells be used in a particular application for treatment. We hope that U.S. regulations allow scientists to use biological materials for research without donor consent if the material is de-identified from the donor, which many of the pioneering iPS studies did. However, genome sequencing could allow donor’s cells to be re-identified. Moreover, donors might support use of their cells in research, but not in sensitive areas such as in reproduction biology or in transplantation or for medical buisness.Reference1. Siddharthan Chandran What are the prospects of stem cell therapy for neurology? BMJ2008;337:a19342 .Sprigg, N, Bath PM, Zhao L, Willmot MR, Gray LJ, Walker MF, et al., Granulocyte-colony stimulating factor mobilises bone marrow stem cells in patients with sub-acute ischaemic stroke: the ‘Stem cell Trial of recovery EnhanceMent after Stroke’ (STEMS) pilot randomised controlled trial. Stroke 2006;37:2979-29833. Rapid responses publ;ished by by Nikola Sprigg, Tim England, Philip Bath “Stem cells for stroke (9 January 2009) for the article ANALYSIS: by author Siddharthan Chandran What are the prospects of stem cell therapy for neurology? BMJ 2008; 337: a1934Professor Pranab kumar Bhattacharya,Professor of.pathology, IPGME&R Kolkata-20Miss Upasana Bhattacharya & Mr.Ritwik Bhattacharya, B.com(cal)Copy Right- Copy Right of this cooment in Journal Nature news belongs to Professor Pranab kumar Bhattacharya and his first degree relatives only as per copy right act & rules of Intellectual Property Right Rules 3D/107/1201a,b/ RDF Copy Right rules/ SPARC copy Right rules-2006/ and Protect intellectual Property Right(PIP) copy right rules of USA-2012.Please do not try to Infringe and be enough careful to use this article for your own safety if you are not direct Blood relation to prof Pranab Kumar Bhattacharya.
- We must await the collection of further epi, Including Grademiological data during coming decades for HPV vaccinesdsil
- Professor Pranab Kumar Bhattacharya, Rupak Bhattacharya & Miss Upasana Bhattacharya Professor Harald zur Hausen , did first identified human papilloma viruses as a key contributors to cervical cancer instead of HSV2 and had been awarded Nobel prize in medicine-2008. Cervical cancer is the second most common cancer among women world wide, with about 5,00,000 new cases each year with around 2,00,000 deaths a year in 3rd world countries compared with 70,000 in developed worlds1. Establishment of causal links between high-risk human papilloma viruses (HPV) and cervical cancer today however can set the basis for new areas of research that include the application of HPV testing and a low cost biomarkers to identify women at high risk of progression to cervical cancer and its precursors. Testing for high-risk HPV by Insitu Hybridization or by Immunohistochemistry in vaginal cytology is more sensitive and has a higher negative predictive value to detect the immediate precursors of cervical cancer (high-grade cervical intraepithelial neoplasia; CIN2/3) than conventional PAP cervical cytology, at the cost of a small decrease in specificity and positive predictive value. higher sensitivities for HPV antigens were noted for any of the DNA-based screening tests and liquid-based cytology is very much costly and technology based. Before administration of HPV vaccines a thorough examination of new technologies in cervical-cancer screening must also be done as HPVprophylactic vaccines are going to be implemented in different developed countries amongst girls. Professor Hausen’s discoveries in 1984s includes detection of novel human papilloma virus types 16 &18, isolation of the virus types 16(60% cervical SCC1) and 18(10% cervical adenocarcinoma1) genomes, expression of specific papilloma virus DNA genes integrated into the tumour host cell genome & identification and molecular cloning of the HPV16 and HPV18 genomes along with E6 and E7 viral genes proteins expressions in cervical cancer cells by applying nucleic acid in situ hybridization technique(ISH), DNA cloning, DNA probe, from nasopharyngeal carcinoma(Nature. 1970;228(5276):1056-8.), laryngeal cancer,( J Virol. 1982;44(1):393-400),from genital warts (Int J Cancer.1974;13(5):650-6)., penile & vulvar cancer and 60%of cervical cancer cases(Curr Top Microbiol Immunol. 1977;78:1-30). These findings have led to an understanding pathogenesis of cervical cancer1, a characterization of the natural history of the human papilloma virus infection, and paved the way for the development of a preventive vaccine “Gradsil [$ 360 for 3 doses of immunization1]”. But whether these vaccines are really effective in preventing only CIN cervical lesions but also cervical cancer and related deaths? Gradsi; has many vaccine related adverse reactions reported.[Gradsil resulted four deaths, three cases of G.B syndromes, related to immunization and 1637 adverse reaction reported by FDA1] In an Australian study 35 girl of 12 years was given HPV vaccine and of them 23 experienced hypersensitive reactions(9%), 13(5.25%) experienced Urtecaria and severe angioedema. Median time of reaction was 90 minutes2 .we must await the collection of further epidemiological data during coming decades. There remains also fear among guardians of young girls for this vaccine administration. In addition, duration of this vaccine’s protection is unclear: do they provide life-long immunity or will booster doses be needed has not yet been decided1 There remains further health policy related questions 1) Should the vaccine be implemented in National immunization policy in LDC countries where incidence of cervical carcinoma is very high?, .It has been however accepted as National immunization programme for 12-13 years old girl by Gradsil in UK from 2009. 2) Gradsil protects 16 and 18HPV plus two non oncogenic types HPV that can cause genital warts. 3) what should be age of vaccination and its cost effectiveness. Cost effectiveness will depend on duration of vaccine immunity lasting[ targeting initial catch up efforts to women of 18-21 years would be more cost effective what I think ]. 4) Will HPV vaccination to be directed towards male boys also? Presently one of my post graduate students in MD pathology is working with HPV 16 in cervical cancer by ISH, in West Bengal, India and found 90% positive in Saquamous cell Cervical cancers of low socioeconomic group women. The primary screening test with ISH for HPV DNA types in cervical tissues or in vaginal cytology smears is really very costly, requires specially trained personnel and sophisticated laboratory infrastructure. We probably need a new HPV test in primary screening for HGSIL.
- References
1) Professor pranab Kumar Bhattacharya, Rupak Bhattacharya, Ritwik Bhattacharya, Upasana Bhattacharya etal “Hope a successful candidate inexpensive HPV vaccine will require further 20-25 years to develop for developing countries” Comments on “Effects of Qudrivallent Human Papilloma virus vaccination” -The Lancet vol 370; N 9592; 22nd sept; 2007; P-1031-32
2) Lew Woek Kap, Nigel Crawford, Mini LK Tang “ hypersensitive reactions to HPV vaccine in Australian School girls- a retrospective cohort study’ BMJ 2008;337;22642;1392
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