Biotechnological applications of stem cells

SUMMARY

Stem cells are undifferentiated and are capable of proliferation / self-renewal there by liberating functional progeny for regenerating affected tissues. The positive effect can be a beneficiary addition to the Neuro - endocrine and Immune triangle of the patient improving his health status.Stem cells are likely to contribute to human health and not to immortality as fantasised by the general public. They bridge the gap of isolating therapeutic agents ,which may lead to prolonged life with less suffering and higher quality. Stem cells are the key to replacing cells lost in many devastating diseases such as cancer, cardiovascular , hepato renal and metabolic syndromes like diabetes. For many of these life-shortening diseases there are no effective treatments as yet and the goal is to find a way to replace those natural processes that have been lost. Devastating diseases leading to prolonged hospitalisation and confinement in bed due to neurological problems such as spinal cord injury and multiple sclerosis etc. Highly specialized cells are required for a physiological function such as Pancreatic islets to facilitate the treatment of chronic diseases such as diabetes. Current challenges include the control of the differentiation process of stem cells and of their development and proliferation once they have been implanted into patients.In order to safely use stem cells or their differentiated progeny , methods of purification and methods of cell-death control will need to be developed. Another vital aspect of stem-cell based therapies is to prevent the rejection by the immune system. There is a long way to go before basic research is applied with stem cell therapy to patients. However, mankind will surely benefit enormously by conducting research in this important area.

AIMS:

To assess the impact of organizing naturally occurring cells (stem cells) in warm blooded animals for benefiting medico - legal cases in humans across the globe.

OBJECTIVES:

This document helps us :

To understand the metamorphosis of medical research and interventions to an all time high in terms of cost effective treatments there by raising the hope of millions across the globe.
To understand the current research in stem cells and its biotechnological applications.
To analyse how stem cell research has touch based the unprecedented response of public from every walk of life.
To reason out the social and ethical issues that have stemmed from this important research activity at the verge of revolutionizing Human relations with the god head.
To evaluate the current health related issues and the ameliorative effect of Stem cell research, if found acceptable to general public in terms of Money - Morals - Mundane issues.

INTRODUCTION:

Human endeavor to lead a healthy and happy life goes back to antiquity. Many researchers across the globe undertaking various forms of treatment measures to alleviate human suffering have realized the role of cells originating from 16 to 32 cell stage of a embryo of warm blooded animals including Humans. Medical scientists conducted extensive studies on to the role of mass of cells originating from the Embryo , Fetus , Umbilical cord , blood forming organs and non reproductive cells / somatic cells in revitalizing the diseased tissue.

The general term Stem cell was introduced to understand the biology of cells that are undifferentiated and capable of proliferation / self-renewal there by liberating functional progeny for regenerating affected tissues. The ability of the embryonic cells to stretch to their maximum limit i.e. to say plasticize them selves has been a recent addition to the scientific knowledge garnered so far. Stem cells in other words are those undifferentiated / unspecialized cell mass that modify themselves in terms of their biochemical and molecular patterns to a new set of cells that transform the recipient tissue and bring a salutary effect. The positive effect can be a beneficiary addition to the Neuro - endocrine and Immune triangle of the patient improving his health status.

Until recently, bone marrow stem cells were the only means available to those in need of a transplant, And the harvesting process involved major surgery. The identification of stem cells in umbilical cord blood and placentas capable of getting harvested directly have opened new vistas of research.

Obtaining Stem cells from umbilical cord has some technical limitations. First, the collectable volume is not typically enough to reestablish an adult immune system. Young and adult age groups are not suitable for cord blood transplantation. But the obtained volume has significant numbers of stem cells that can be stored and propagated indefinitely. It doesn't lead to medical risks for the recipient, and has a low graft-versus-host-disease (GVHD).In order to offset the allergic reactions during transplantation, scientists conduct tests related to hypersensitivity and determine the suitability with 6 genes called HLA genes.

Though there are many benefits of stem cells, biotechnological interventions portend to have negative potential uses. For example, one of the biggest threats is that of human cloning as perceived by moralists and religious heads. Therefore the following issues have to be clarified namely:

What are stem cells and what promise do they provide,
The moral issues that tend to stem further research along,
public and private funding for the research,
And the stance that socio - legal experts take regarding funding and medical benefits there of.

There are three different types of stem cells with potential health benefits : human embryonic stem cells (ES cells), human embryonic germ cells (EG cells), and human adult stem cells (AS cells). The EG cells and AS cells, have shown to be with limited potential and with limited success in the lab. Organizations have been in favor of funding adult stem cells since these cells are found in all humans. They are found in various human tissues, but they have only been successful in the lab when they have been combined with ES cells. Human embryonic stem cells have shown the most potential in the labs on their own.

Around the early 1970s, stem cells were discovered while studying mice. However, it was during the 1980s that the research started showing its benefit toward humans with human tissue testing. Most of the beginning research was focused on human reproduction, which led to the first birth from a frozen embryo. While this was the start of the research, scientists started to realize that the early stages of the stem cells could be turned into a variety of other human tissue. Over the last few years, the issues relating to stem cells have become more in the public eye.

Though this may be one case that may go against others like it, it shows that even throughout our courts today there are still some questions about how we should classify embryos. Most scientists believe that to discontinue with the research would be unethical. How could such promising research be ignored? Government officials' position, on the other hand, has a more difficult time because they are the ones who have to balance and compromise the public and scientific views.

Private funding is still available, but it has its disadvantages compared to government funding. In the private sector, there is no one to regulate how the research is conducted. There have been other cases where experimentation in the private sector has led to "egregious abuse of research. When the government is involved with an issue that is as controversial as one like stem cells, the private sector tends to follow the governments lead.

Scientists believe that this research will lead to many cures for several diseases. Stem cells can be taken from other sources like; adult cells, from the umbilical cords that are discarded after a mother has a baby and from human placentas. There are many diseases, which have already been helped by the adult stem cells. Most scientists however believe that embryonic stem cells hold the most promise for a range of cures because these cells can develop into any of the bodies tissues.

APPLICATIONS: Stem cells have immense potential for cell-based (transplantation)therapy, following lineage-specific differentiation, for various human diseases such as diabetes mellitus,Buerger's disease,Osteo arthritis,Acute renal failure,chronic liver failure, myocardial infarction, Parkinson's disease, Alzheimer's disease etc. In recent years, there have been attempts to use somatic stem cells (from the bone marrow, umbilical cord) for cell therapy for the above diseases. Today's evidence has been favoring differentiation of human ES-cells to functional neuronal cells or islet cells and for the successful experimental cell-transplantation in model organisms, which has been quite promising. In this context, environmental and growth factors regulating differentiation of ES-cells are aggressively being studied world over to address neural, cardiac and metabolic disorders like myocardial infarction, spinal cord injury and leg ischaemia.

Stem cells aid in renewing blood and bones.

Stem cells from plucked hair can be used in Skin replacements.

Adult Keratinocyte stem cells regenerate epidermis and aid in treating burns and skin ulcers.

Stem cells provide a demanding chemical in patients with Parkinson's disease.

Embryonic and adult-derived stem cells are today employed for cardiac repair.

Various stem cells like ES cells, resident cardiac stem cells, myoblasts, adult bone marrow-derived cells including mesenchymal cells endothelial progenitor cells and umbilical cord blood cells, were found to be the possible sources for regenerating damaged heart tissue.

Leukaemia Stem cells, more analogous to progenitor cells employ embryonic stem cell like genetic programmes and are promising targets for therapy.

Adult stem cells also aid in Lung repair. It has been found that the pulmonary stem and progenitor cells assist in homeostasis and regeneration of the Respiratory system.

The ethical debate is that potential life is been destroyed in order to perform this research. There is another side of the argument and that is if these embryos holding the stem cells are going to be wasted and thrown away shouldn't they be used for the greater good. Some researchers argue this statement with the belief that the five day old cluster of cells is not an embryo or an individual, it has the potential for life but isn't life because it can't survive on it's own.

Few people paid much attention to biotechnology until Dolly. Then everyone realized that this was a major issue. There were many moral and ethical questions at hand with cloning. People didn't know what to think of it. It could be good because cures for cancers can be found, important medicines can be created. But some disagree. They feel that there are a quite a few things wrong with the issue of cloning. It harms the animals because there are hardly any laws governing the use of cloning. Cloning creates a lack of diversity, leaving the whole species vulnerable to deadly diseases, and biotech companies will misuse cloning for profit, and not care about anything else.

Some of the molecular events that tend to happen in the pluripotent stem cells are as follows:

Changing the DNA of eggs, sperm or embryo so that offspring will also contain the new DNA.
An egg cell whose nucleus has been removed or destroyed.
Undifferentiated multi potent precursor cells that are capable of either continuing on as stem cells or undergoing differentiation into one or more specialized types of cells.
Those containing genes from a species other than their own.
This integration does not occur in every embryo, but about 10% of the animals born following injections will reliably incorporate the new material.
Cloned animals produce substances,that humans need, in their milk.

Adult stem cells have been used for transplants therapy for quite a long time in medical history. The basis of transplantation-based therapies can come from cells involved in tissue repair from heart and brain.

Hematopoietic stem cells make up for red blood cells, wbc's and macrophages. Mesenchymal stem cells are present in many tissues like bone in the form of marrow stromal stem cells, and skeletal stem cells giving rise to a variety of cell types that support blood formation.

Neurons, dendrocytes and astrocytes form the stem cells of brain.

The deep pits in intestinal tract are the home ground for a variety of cell types: absorptive cells, goblet cells, Paneth cells, and entero endocrine cells. Similarily the basal layer of the epidermis of skin form the nidus for dermal stem cells.

Few advances in Science and Technology have generated as much controversy as the use of human embryonic stem cells (hESCs) harvested from the pre-implantation embryos. The potential of Stem cells is to replace dead or damaged cells in any tissue of the body. In addition, hESCs offer a new model system for studies on the basic mechanisms of normal and abnormal development biology as also for drug discovery. With success of growing human embryonic stem cells without feeder layer, derivation of histocompatible hES from embryos created by Somatic Cell Nuclear Transfer (SCNT) and tissue specific differentiation of umbilical cord/bone marrow derived mesenchymal and haematopoeitic stem cells, there is a need to generate public confidence in potential benefit of stem cell Research to human health and disease.

Categorization of research on stem cells:

According to the source of stem cells and nature of experiments, the research on human stem cells is categorized into following three areas:

Permissible research areas
Restricted research areas
Prohibited research areas

Permissible areas of research are:

In-vitro studies on established cell lines from any type of stem cell viz. hES, hEG, hSS; or fetal/adult stem cells may be carried out with notification to IC-SCRT, provided the cell line is registered with the authorized agencies and obtained by GLP.
In-vivo studies in small animals with established cell lines from any type of stem cells viz., hES, hEG, hSS, including differentiated derivatives of these cells, provided such animals are not allowed to breed. This includes preclinical evaluation of efficacy and safety of human stem cell lines or their derivatives.
In-vivo studies on experimental animals (other than primates) using fetal/adult somatic stem cells from bone marrow, peripheral blood, umbilical cord blood, skin, umbilical cells, dental cells, bone cells, cartilage cells or any other organ (including placenta), provided appropriate consent is obtained from the donor.

Restricted areas of research:

Creation of a human zygote by In-Vitro Fertilization or any other method with the specific aim of deriving a stem cell line for any purpose.It would be required to establish that creation of zygote is critical and essential for the proposed research. Informed consent procedure for donation of ova, sperm, somatic cell or other cell types as detailed by scientific guidelines.
If there is a possibility that human cells could contribute in a major way to the development of brain or gonads of the recipient animal, the scientific justification for the experiments must be strong. The animals derived from these experiments shall not be allowed to breed.

Prohibited areas of research:

Any research related to human germ line genetic engineering or reproductive cloning.
Any in-vitro culture of intact human embryo, regardless of the method of its derivation, beyond 14 days or formation of primitive streak, whichever is earlier. Transfer of human blastocysts generated by parthenogenetic or androgenetic techniques into a human or nonhuman uterus.
Any research involving implantation of human embryo into uterus after manipulation.

CONCLUSION:

Stem cells are likely to contribute to human health and not to immortality as fantasised by the general public. They bridge the gap of isolating therapeutic agents ,which may lead to prolonged life with less suffering and higher quality. Stem cells are the key to replacing cells lost in many devastating diseases such as cancer, cardiovascular , hepato renal and metabolic syndromes like diabetes. For many of these life-shortening diseases there are no effective treatments as yet and the goal is to find a way to replace those natural processes that have been lost. Devastating diseases leading to prolonged hospitalisation and confinement in bed due to neurological problems such as spinal cord injury and multiple sclerosis etc. Highly specialized cells are required for a physiological function such as Pancreatic islets tofacilitate the treatment of chronic diseases such as diabetes. Current challenges include the control of the differentiation process of stem cells and of their development and proliferation once they have been implanted into patients.In order to safely use stem cells or their differentiated progeny , methods of purification and methods of cell-death control will need to be developed. Another vital aspect of stem-cell based therapies is to prevent the rejection by the immune system. There is a long way to go before basic research is appllied with stem cell therapy to patients. However, mankind will surely benefit enormously by conducting research in this important area.

REFERENCES:

Guidelines for Stem Cell Research and Therapy from, http://unisci.com/stories/20021/0211021.htm
Guenette, S. Y., Tanzi, R. E. Neurobiol of Aging 1999; 20: 201-211 from http://unisci.com/stories/20021/0211021.htm
VanLeuwen, F. Progress in Neurobol 2000; 61: 305-312
Human Pluripotent Stem Cell Research: Guidelines for CIHR-Funded Research available on CIHR IRSC site created on 4/9/2003
National Academies Guidelines for Human Embryonic Stem Cell Research available on http://www.nap.edu/catalog/11278.html
National Research Council, US ICMR Ethical Guidelines for Biomedical Research in Human Subjects 2000
ICMR Ethical Guidelines for Biomedical Research in Human Participants 2006
Stem cell information for the public from the International Society for Stem Cell Research (ISSCR) from http://www.isscr.org/public
Medline Plus is a consumer health database that includes news, health resources, clinical trials, and more from http://www.nlm.nih.gov/medlineplus/stemcells.htm
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A commercial, online newsletter that features stories about stem cells of all types http://www.stemcellresearchnews.com
The Hebrew University of Jerusalem (2009, November 30). New stem cell technology provides rapid healing from complicated bone fractures. ScienceDaily. Retrieved December 4,2009 from http://www.sciencedaily.com� /releases/2009/11/091130112411.htm
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