Embryonic Stem Cells: Can neural stem cells cure Diabetes Mellitus type 1?

The proposal alone of using human embryonic stem cells for the purpose of medicinal research has caused intense debate among many political and religious groups. Research into this field, requires one to analyse the priorities of medical research alongside the prosperous future it could provide.

Embryonic Stem Cells

Stem cells are unlike other cells. They are unique in that they are unspecialized and thus retain the ability to develop into any of the wide spectrum of cells possible (in theory) within the human body (pluripotency). The lack of tissue specific structures enables stem cells to form specialised cells in a process known as differentiation.

Embryonic Stem cells differ from other variances of stem cells due to their capability to replicate themselves in a laboratory indefinitely. More importantly however, they can generate into any type of cell within the human body. Other types of stem cells, such as Adult stem cells, are limited to what type of cells they can form and this has resulted in their use being very limited.

Diabetes mellitus (Type 1)

Type one diabetes is an ‘auto-immune’ disease. Those who are diagnosed with d.m.t.o,* are unfortunate in that their immune system creates antibodies that attach to the beta cells in the pancreas which destroy the cells that make insulin. In rare circumstances, it has been caused by inflammation of the pancreas but this cause has only affected a miniscule proportion of sufferers. (Kilvert, 2008) If left untreated the consequences could be fatal and potentially lead to death. There are numerous serious problems associated with diabetes if not treated ranging from Atheroma to Blindness. In the UK alone, 1 in 250 develops type one diabetes but it can increase to 15 in 250 if a first degree relative has been diagnosed with it. (www.diabetes.co.uk, 2009) As of late 2008, it has been estimated that eighteen million people have d.m.t.o worldwide which illustrates just how vital a potential cure could be. (WHO – World Health Organisation, Nov 2008)

The complications of the treatment of d.m.t.o are caused by the necessity to ensure the correct amount of insulin is taken. Excess insulin can cause the glucose level to plummet thus causing hypoglycaemia or adversely a lack of insulin could cause the afore mentioned problems of untreated d.m.t.o.. At present, the current treatment to ensure a patient stays healthy, is for them to take insulin injections 2-4 times a day for the rest of their lives. (www.diabetes.co.uk, 2009)

Why specifically Embryonic Stem Cells?

In order to understand and analyse the results and progress of research into this field, it is imperative to understand why embryonic stem cells are being focused on a solution as opposed to other forms of stem cells.

Somatic (Adult) stem cells have been leading stem cell research in the past as it never necessarily conflicted with the majority of ethical or religious groups and their beliefs. They are rare undifferentiated cells that can be found in differentiated tissues with a capacity for self renewal in addition to differentiation, although this ability is limited. There is a tiny amount of somatic stem cells within each tissue and upon these being removed, their capacity to divide and multiply dwindles leading to difficulty in obtaining large amounts of somatic stem cells.

As research progressed however, the flaws of these stem cells were exposed. The number of cell types that they can develop into are restricted which hinders its versatility and its application to cure a variety of diseases. Somatic cells also have an increased chance of carrying mutations of the DNA compared to its human embryonic stem cell counterpart. The reason being the adult cells could have mutated over the respective person’s lifetime in a cell division process known as mitosis. Embryonic stem cells have had less exposure to this process and thus regenerate at a pace that is much greater than that of adult stem cells.

In the placement of a culture, (Growth of cells in vitro in an artificial medium for research or medical treatment (The National Institutes of Health resource for stem cell research, 2009)), embryonic stem cells are able to divide infinitely and with relative ease in comparison to somatic cells. Having said the above, adult stem cells have a superiority in that the cells are the patient’s own cells, and there is no chance of their body rejecting the cells as they are compatible. There is no need for immune suppressing drugs which would otherwise occur with embryonic stem cells making the patient vulnerable to other diseases.

The main reason for deciding on embryonic stem cell research in particular was due to the key aspect that it could differentiate and divide easier and to a greater extent making it very versatile and therefore seemingly have a higher potential to cure a disease such as d.m.t.o. The points that have been made as of yet, are to provide a basic knowledge and all will be explained further within the article alongside a more detailed analysis of the points made.

Can Embryonic Stem Cells cure diseases?

Although embryonic stem cells can be grown in culture/vitro, research is still at a very premature stage. Before even considering its potential to cure d.m.t.o, it must first be deduced if embryonic stem cells can cure diseases at all.

From an outside perspective, it would appear that the possibilities are endless, and that embryonic stem cells could well become the 21st century penicillin. However in reality, the human body is a complex being and there are an enormous number of complications to overcome e.g. the patient’s immune system rejecting the new cells and destroying them.

Regardless of the fact that research is in its premature stage, there have been encouraging reports. In the United States of America, researchers used embryonic stem cells to cure mice who were bred to suffer from a Parkinson’s-like condition. Embryonic mouse stem cells differentiated into neurons in a lab dish. They were then transplanted into a rat with Parkinson’s disease (PD), and the isolated cells formed functional connections and reduced disease symptoms. The researchers found that the grafted cells established functional connections with surrounding brain cells and began to release dopamine. The rats that received the differentiated cells showed significant improvements in symptoms during behavioural tests. Since undifferentiated embryonic stem cells sometimes multiply out of control and form tumours, the researchers measured the number of cells in the grafts at several time points after the transplants. The number of cells in the grafted areas stabilized by four weeks after the transplants, and none of the rats developed tumours. (Frazin)

Albeit, it may only be in mice but the results are very promising in particular because there were no tumours formed and with the brain cells releasing the vital catecholamine dopamine. The latter is of particular interest as if related to the context of d.m.t.o., it would be beta cells releasing the hormone insulin so there are some similarities in that the embryonic stem cells were used in order to differentiate into a cell that releases a chemical of some sort.

Humans and rats have the same basic physiology, similar organs, and similar body plans. Both control body chemistry using similar hormones, both have nervous systems that work in the same way, both react similarly to infection and injury. (How Humans Are Like Rats, 2003) This likeliness between both humans and rats increases the relevancy of the results of the experiment. Nonetheless, there is no guarantee that it will work on humans and it would be naive to believe it would be directly transferable to humans from rats without flaw.

On the other hand, there has been no embryonic stem cell research successfully tested on humans. Even the latest breakthrough by Geron Corporation, the first group to ever obtain the approval of the FDA to conduct clinical trials, has been delayed. Despite eight years of intense research, an abnormal amount of cysts caused the company to delay trials (http://singularityhub.com/2009/09/02/geron-explains-why-first-embryonic-stem-cell-clinical-trial-is-stalled/, 2009). There has not been an opportunity for anyone to safely test on humans as of yet. Until, an organisation has perfected testing on animals, it is only sensible to postpone the testing of humans, but the results are promising. With most if not all medication being first tested on animals, it shows that results from animal testing are relevant and valid to use in relation to embryonic stem cells potential human use as has been the practice for several decades now in pharmaceuticals and medicine. It would be reasonable to conclude that embryonic stem cells do in fact have the potential to cure diseases, but maybe not in the immediate future. A more thorough conclusion can only be made with some evidence of human testing but with none being conducted; only time will give a concrete conclusion but at present, the results are looking highly promising.

Evidence of embryonic stem cells to cure Diabetes mellitus type one

An important factor that must be considered in this research article is what evidence has already been conducted that would suggest it is or would be a cure to d.m.t.o..

Dr Ron McKay of the Laboratory of Molecular Biology and his colleagues described a series of experiments in which they induced mouse embryonic cells to differentiate into insulin-secreting structures that resembled pancreatic islets. Dr McKay and his colleagues began with embryonic stem cells and let them form an aggregate of cells containing all three embryonic germ layers (known as embryoid bodies). They then selected a population of cells from the embryoid bodies. Using a sophisticated five-stage culturing technique, the researchers were able to induce the cells to form islet-like clusters that resembled those found in native pancreatic islets. The cells responded to normal glucose concentrations by secreting insulin, although insulin amounts were lower than those secreted by normal islet cells. Quoted by Dr McKay “This system is unique in that the embryonic cells form a functioning pancreatic islet, complete with all the major cell types. The cells assemble into islet-like structures that contain another layer, which contains neurons and is similar to intact islets from the pancreas. (Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets, 2004). This outcome is fascinating achievement as what is has enabled to do is, begin to partially cure d.m.t.o. even if it is in the case of mice. Although the levels of insulin produced were not the same as that of healthy islet cells, it is significant progress and with some alterations and tweaking, the future is looking hopeful to cure diabetes type one, albeit in mice. That said, a cure in mice and rats is often not far from that of humans as explained in paragraph three and four on page four.

Research conducted during the last decade has also provided more evidence that human embryonic cells can develop into cells that can and do produce insulin. Dr Melton, Nissim Benvinisty of the Hebrew University in Jerusalem, and Josef Itskovitz-Eldor of the Technion in Haifa, Israel, reported that human embryonic stem cells could be manipulated in culture to express the PDX-1 gene; a gene that controls insulin transcription. In the experiments, researchers cultured human embryonic stem cells and allowed them to spontaneously form embryoid bodies. The embryoid bodies were then treated with various growth factors, including nerve growth factor. PDX-1 is associated with the formation of beta islet cells and thus these results suggest that beta islet cells may be one of the cell types that spontaneously differentiate in the embryoid bodies. Researchers now think that nerve growth factor may be one of the key signals for inducing the differentiation of beta islet cells and can be exploited to direct differentiation in the laboratory. (PNAS 97 (21): 11307-11312), (Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells, Melton, Douglas A.) Complementing these findings is work done by Jon Odorico of the University of Wisconsin in Madison who in preliminary findings, has shown that human embryonic stem cells can differentiate and express the insulin gene but it still remains in early stages with many hurdles yet to overcome. (The National Institutes of Health resource for stem cell research) Once again, another encouraging report of results, these results are of particular importance as it allows guidance of where to continue next e.g. consider intensive research into nerve growth and then using those results to continue researching into curing d.m.t.o. using embryonic stem cells.

Possibly the most important finding in the last couple of years is that of Novocell who report that they managed to convert human embryonic stem cells into insulin-producing cells. The researchers found that when they injected these human cells into diabetic mice, the treatment alleviated diabetes in the rodents. The new technique used will provide doctors with a bulk supply of clean, uncontaminated insulin-secreting cells for use in diabetes patients. It is a controlled process where the quality of the cell being implanted remains the same every time an implant is done. Unfortunately, much of the science behind this new method remains behind closed doors and is difficult to access but a Dr Curt Freed, director of Neurotransplantation from the University of Colorado School of medicine was quoted saying “This is an extraordinary breakthrough by scientists at Novocell, this discovery holds promise for everyone with insulin-requiring diabetes. While outcomes of clinical trials are unpredictable, these cells are likely to be tested in patients soon. (ABC News Medical Unit, 2008) With little scientific information being released, it is difficult to come to a conclusion yet the basic outline seems to be fantastic news particularly as it was found less than a year ago. With the backing of a neutral head researcher of another organisation, Dr Freed, also meriting Novocell on their discovery alongside ABC News Medical unit, it is a huge advancement in the race to find a cure.

Despite the promising results, a working solution is still quite far away. There are several complications to overcome before this becomes a working and viable solution. As far as embryonic stem cell research is considered, we have come to a stage where what was one of the biggest concerns, the production of tumours, no longer occurs (in most cases) immediately after the transplant of the embryonic differentiated islet cells is completed. The cause of d.m.t.o. is due to the immune system destroying the cells that produce insulin. A major question is “Will the human body detect the new cells as foreign?”, and the answer to that is yes. Therefore that leads to a scenario where immunosuppressive drugs must be taken in order for the immune system to not destroy the new cells. That in turn leads to a very dangerous situation where the respective person is left with a very vulnerable body where they are susceptible to a variety of diseases. This would mean that immunosuppressive drugs (along with immunosuppressant treatments) would probably have to be taken for the rest of their lives – in the same way a sufferer of d.m.t.o. has to take insulin injections regularly for the rest of their lives. Another key factor to consider is for what period of time will the cells remain fully differentiated? If this is not answered, then the potential for cells to become carcinogenic and for tumours to form is always a risk. it is im[ Yet, research has not quite reached that advanced stage but it is important to drive home the idea that despite the encouraging reports, collectively, there will be future complications and difficulties which must be overcome.

Article by Abiram Ganeshanathan, London

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