Molecular Biology & Genetic Engineering
MSc Biotechnology, Bioprocessing & Business Management
The biotechnological applications of stem cells
The focus on Stem Cell Research recently has increased immensely mainly due to their potential utility in numerous biomedical applications. Stem cells have changed our perception on ways and methods to treat previously thought untreatable diseases. Apart from prospective disease prevention and treatment it also includes ways of identifying new molecular targets, discover and develop new drugs and can also be used to test their safety. Because of their self-renewing property they can be continuously cultured and give rise to specialised cells of the human body through differentiation.
This essay introduces the concept that is Stem Cells and also describes various applications which are/can be used for treatment and control of various different kinds of diseases in humans. A long list of potential biotechnological applications of Stem cells has been discussed. It also explains in brief the challenges involved with stem cell research.
It has been known by Scientists for centuries that there are animals which have the ability to regenerate some missing parts of their bodies. Like goldfishes and the newt even humans share this ability. Though it may not be possible for us to replace say a lost finger or a lost limb but the human body is continuously regenerating skin, blood cells and other tissues. The cells responsible for this regeneration were first indentified in experiments during the 1950s which established the existence of stem cells that led researchers to develop bone marrow transplantation which is a widely used therapy today. This research led to the hope that one day using biotechnology these stem cells can be used to treat diseases in medicine.
Stem cell research is now being pursued in order to achieve major advances in medical science. Therapies are being developed by scientists that use the regenerative power of stem cells to provide a cure for people suffering from disease like diabetes, cancer, spinal cord injuries, Cardio vascular diseases and many other disorders. Overall studies in stem cell research will help scientists to understand human biology in a lot better way. Unfortunately biotechnological applications of stem cells also has a darker side relating to ethical implications and moral dilemmas among many other challenges associated with this budding process.
WHAT ARE STEM CELLS?
It is interesting to know that stem cells are present in all of us from the early stages of human development, all throughout life until death.
Stem cells are basically unspecialised cells that have the property to self-renew indefinitely and can also differentiate into other mature cell types with specialised functions. Differentiation is the process by which cells attain new functional and morphological qualities. ( Theise and Krause, 2002).
This property of stem cells to exhibit the property of self regeneration and differentiation or which is known as "stemness" is currently being studied by gene expression profiling methods. ( Ramalho-Santos et al., 2002, Sato et al., 2003) In the case of humans stems cells have been identified in either the inner cell mass of the early embryo i.e. generally in the tissues of the embryo, placenta or the umbilical cord or otherwise in adult organs. In the case of cells derived from the adult organs stem cells have the property of giving rise to multiple cell types from that particular organ for example neural stem cells can give rise to three different cell types namely astrocytes, glial cells, neurons in the brain.
Two terms associated with stem cells are plasticity(ability to differentiate into a type different from the original cell type) and multipotency (ability to differentiate into multiple type from multiple organs)
TYPES OF STEM CELLS
1) EMBRYONIC STEM CELLS (ES)
A blastocyst can be described as the 5 day old pre implantation embryo after fertilisation. It is the precursor for human formation and can develop into a complete organism. The cells in the inner lining are multipotent in nature and can give rise to all cell types constituting the body.
Scientists extract these inner mass cells for use as ESCs. These cells were isolated in 1998 (Thomson et al.) and have been shown the same plasticity as Mouse ES cells.
Sources of ES cells
In Vitro Fertilisation- The process of IVF involves retrieval of the woman's eggs through a surgical procedure.
Nuclear Transfer- this involves the process by inserting the nucleus of an already differentiated adult cell into an enucleated egg cell.
2) ADULT STEM CELLS
Adult stem cells are generally found well within the human body surrounded by millions of other cells. These cells can renew themselves inside the body and thus making clones of itself for the lifetime of the organism or in order cases form cells of the organ of origin.
Sources of Adult Stem Cells
Sources of adult stem cells include the blood, the bone marrow, the eye, the brain, skeletal muscles, dental pulp, liver, skin, pancreas and the lining of the gastrointestinal tract. It has been shown by studies that some of the adult stem cells are multipotent. For example stem cells obtained from bone marrow (mesodermal) have been shown to differentiate into three different types of brain cells (ectodermal) (Mezey et al., 2000) and also that the stem cells from the brain have been shown to differentiate into muscle tissue and blood cells (Bjornson et al, 2000) though more research has to be done to verify the findings.
BIOTECHNOLOGICAL APPLICATIONS OF STEM CELLS
Biotechnological applications of Stem Cells in the use of medicine and human health are immense. Research in stem Cells promises to show as a new and innovative way towards curing or at the least controlling diseases.
1) HELP IN REDUCING BRAIN DAMAGE
Recent studies have shown that using implanted stem cells have been used to preserve and replace dying nerve cells in mice which have induced human like diseases. This research opens scope for better understanding of how the human brain develops and ages and also how stem cells could be used to treat diseases and injuries.
In the research mice having brain damage caused by cerebral palsy and strokes received implants which resulted in immediate replacement of many missing cells. Other experiments showed that stem cells were able to rescue injured nerve cells of aged mice whose brain had reached an equivalent of Parkinson's disease in humans after normal aging.
These experiments on the ability of neural stem cells to be able to repair and protect the brain allows us to speculate that other cells in the body could be used for the same purpose such as heart, muscles, liver etc,
For diseases such as Parkinson's disease and Alzheimer's disease which causes direct brain degradation stem cells could be a ray of hope.
2) HOPE FOR CANCER
Why has it been observed that some cancers are so hard to remove even after many rounds of chemotherapy? The main reason is due to several abnormal stem cells. These are the cancer stem cells which were first identified in 1997. Similar to stem cells tumour stem cells are found in small numbers but have the capacity to replicate immensely and give large number of cells, and unlike normal stem cells these lack the controls which tell them to stop dividing. Normal chemotherapy destroys most cancer cells but supposing any cancer stem cells remain the cancer will reappear.
Due to their inherent tumoritropic migratory properties they can be used as delivery vehicles for the targeting and treatment to isolate tumours and also to metastatic disease. Stem cells can be easily engineered in vitro by incorporating tailored transgenes with antitumor characteristics thus forming therapeutic tumour seeking vehicles. Some of the transgene effects include promotion of immune responses, direct tumour cell killing, prodrug activation schemes as well as oncolytic virus production. Some of these methods have been proved to be correct in several studies which deal with assessing the feasibility for the treatment and establishing these methods for real time analysis and in vivo studies.
Research done relating to differences in gene expression of normal and tumour stem cells will help in development of treatments where the root cause of the issue i.e Cancer stem cell are targeted.
3) APPLICATION IN SPINAL CORD INJURIES
With the discovery of neural stem cells it has revolutionized the way scientists look at treating spinal cord injuries. The chance of full recovery from paralysis can now seem like a possible option. Regeneration of neurons and glial cells is the basis of this application.
In 1995 Frissen reported that the presence of nestin increased in response to injury. Nestin is a protein which is expressed by stem cells. It has been realised that stem cells do respond to spinal cord injury not only for the purpose of reconnecting with the neurons. One of the two major study areas of spinal cord regeneration is the triggering of neurotrophic factors. ES cells can also be derived from fetal spinal cord in order to implant into damaged spinal cord. When treating patients with ES cells they can either allow ES cells to mature into CNS cells or they can directly implant the cells into the brain. The work by McDonald in 1999 showed us that even though stem cells could be successfully used, there are still some years left before they can be brought about to practical applications.
The possibility of stem cells to develop into neural cells opens new doors and changing the common beliefs towards adult neurogenesis.
4) REPAIRING HEART DAMAGE
It has been observed that stem cells obtained from different sources allows us to overcome challenges associated with cardiovascular damage (Murry et al. 2006). Human and mouse ES cells have the ability to differentiate into vascular lineages and cardiomyocytes and have also allowed us to understand the properties of pluripotent cells properly. Though because of their immunogenicity there is a risk of them turning timorous as well other ethical issues due to their embryonic origin. In this regard the use of Bone Marrow derived cells (BMC's) are proven to be advantageous because of these ethical implications and also since they can be easily isolated from patients, resulting in autologous cells which are ready for transplantation without worrying about immune rejection.
5) USE IN HAEMATOPOESIS
On recovering from a wound the human body replenishes its lost blood cells by calling upon some semi-specialised cells known as hematopoietic stem cells which are present in the blood and the bone marrow. For many years scientists have been using these stem cells for the treatment of diseases such as sickle cell anaemia, leukaemia, bone marrow damage and other metabolic disorders as well as immunodeficiency's because of which the body loses its ability to produce healthy blood cells. From white blood cells to blood clotting platelets, hematopoietic cells can give rise to all kinds of cells. It may even be possible for these cells to produce other kinds of cells, but no proof has been found yet.
Formerly the only method off using these cells for therapies was through bone marrow transplants. This particular process was invasive, painful and the chances of rejection were high. Recently scientists have figured out ways to extract hematopoietic stem cells from the umbilical cord and also from the placenta at birth. These cells since being extracted from the individuals own body have lesser chance of rejection and are also more accessible since they are extracted from the blood.
6) AS A FIX FOR DIABETES
In the case of patients with type 1 diabetes the beta cells of pancreas which produce the insulin are destroyed due to the person's own immune system. Hence without the insulin produced the body cannot uptake glucose and hence starves, thus the patients require insulin injections every day. Currently the only cure is pancreatic transplant from a recently deceased donor.
Adult stem cells have not been found in the pancreas though scientists have been successful in using ES cells to produce insulin-producing cells. The combination of beta-cell transplants incorporated with methods to fix the patient's immune system such as chemotherapy that destroy malfunctioning cells in the immune system coupled with blood transplants to recover white blood cells could help in the treatment of people suffering from type 1 diabetes.
7) AS VEHICLES FOR GENE THERAPY
Stem cells also have application as being used as vehicles for gene therapy. For example adult stem cells namely hematopoietic stem cells which can be obtained from the bone marrow can be in vitro manipulated and can be retransplanted back into the patient by injecting them into the blood stream. Apart from them another adult bone marrow derived stem cell type with use in gene transfer is the mesenchymal stem cell. Also recently the multipotent adult progenitor has also been found to be useful. The normal method of introducing a therepeutic gene into a hematopoietic cell is by the use of a vector namely the retrovirus or even the adenovirus. A problem of this process is the fact that due to lack of specificity of the gene it may affect the functioning of the normal genes surrounding it in the chromosome. Research advances in using mouse hematopoietic stem cells may ultimately be transcribed into human use.
8) OTHER APPLICATIONS
Stem cells furthermore have several other applications-
- Production of skin for use in skin grafts.
- As a possible cure for baldness.
- In the regeneration of teeth.
- Lens and retina regeneration.
- Transplantation for auditory nerve replacement.
- Curing amyotrophic lateral sclerosis type diseases.
- Rectifying graft vs. host diseases like Crohn's disease.
- Producing spermatozoan cells for curing infertility.
ETHICAL CHALLENGES IN STEM CELL RESEARCH
Though the application and potential of stem cell research may be huge there are several ethical issues associated with it.
Comparison of Embryo to a person
This controversy relates to the nature of human life along with the moral and legal status of a human embryo. Questions based on whether the blastocyst from which the cells where removed would go on to form an individual. Various religions and traditions have differences in opinion some supporting the use of stem cells from embryo's and some not.
Stem Cell research and reproductive cloning
Stem cell research has commonly been misunderstood and compared with reproductive cloning though the results and goals of the either two are quite different. This is mainly because of the fact that both the procedures involve a similar step which is known as 'nuclear transfer' and has resulted in several ethical debates for several years.
Implications of Human-Animal Chimeras
Chimeras are basically organisms which are composed of cells/tissues from more than one individual. Questions have been raised on the suitability of incorporating non-human components in humans. Also the final product is deemed as 'unnatural'.
Stem cells are different and put forth immense opportunities in research for future potential therapy. May it be embryonic stem cells or adult stem cells they both can be used to replace or at least repair damaged cells and tissues in animals. Research and models based on animals will soon be incorporated to human use. Though there are many questions which cannot be answered yet with regard to how soon several therapies will be actually put into practical use and which kinds of stem cells will lead to the best kind of treatment.
No one can predict the future of stem cell research mainly because these are just the early days of the science of stem cell technology. The applications of stem cells presently are itself novel and it's only a matter of time before we know what the future holds of us. Though like all breakthrough technologies even stem cell technology has its share of problems specifically pertaining to legal and ethical issues, but in order to reach its full potential it must overcome all these barriers and come out on top.