Stem Cells and Limb Regeneration: The Possibilities and Limitations

Introduction

I will be mostly focussing on the use of stem cells and their research as the method of attaining regrowth of limbs as it is the most researched and thought to be the most likely to create results. This is due to studies into some of the animals whom are capable of limb regeneration, such as lizards and axolotls, which were found to always retain their pluripotent stem cells, which have the same potency as our embryonic stem cells. So, for example, if the tail of a leopard gecko was cut off the pluripotent stem cells would then rush to the stump to then form a regeneration blastema which will then get all the pluripotent stem cells located there to differentiate and create the necessary cells to form tissues, bones, etc. However, through evolution humans don’t require this as instead of focussing a very large amount of energy to regrow limbs naturally which would also take a considerably longer time due to us being much larger members of the animal kingdom, we regrow skin to cover the wound and prevent infection, therefore not requiring these pluripotent stem cells past the embryonic stages. Due to this fundamental discovery of the differences between how humans and a few select animals cope with a loss of a limb, researchers have realized that stem cells are the best chance for the regrowth of limbs, which is the reason I will mostly be discussing stem cells as the major method of regrowth of limbs.

There are three main types of stem cells used in research, and therefore will be the only ones I will talk about, which are: Adult/tissue stem cells, embryonic/pluripotent stem cells, and induced pluripotent stem cells/iPSCs. Adult stem cells come from different parts of the body, they’re specific to that certain part of the body(eg. Liver stem cells can regenerate liver tissue). These cannot become other specialized tissue and are limited to only their specialized tissue. Pluripotent stem cells are the most powerful stem cell used. This is because they can be seen as “blank slates” due to the fact that they have the ability to become any specialized cell and are not limited to becoming one specialized tissue unlike adult stem cells. However, the method of attaining these stem cells causes many issues for people in a similar manner to how abortions do. This is because traditionally embryonic cells were only obtainable through growing a human embryo into a cluster of cells of which then contain an inner cell mass. It is the inner cell mass which contains an abundance of embryonic stem cells. However, after this inner cell mass is removed, the embryo is ultimately destroyed which causes many moral issues due to the destruction of this embryo which could have created life. This removal process can also cause problems to the patient due to the medication required to be taken during the process such as ovarian hyperstimulation. This is a reason why iPSCs were created which are pluripotent cells which have been derived from adult tissue using newly discovered scientific technology. They are capable of becoming any cell type similar to pluripotent stem cells. Reprogramming stem cells in order to then create iPSCs then involves genetic manipulations, this can therefore cause differentiations that aren’t present in pluripotent stem cells naturally. This method to create iPSCs is very costly however in order for the process to be underdone correctly and safely. Due to this, embryonic stem cells are more accurate and economically efficient but at the cost of it having many moral issues, whereas iPSCs don’t but at a larger price with the possibility of creating incorrect results due to the differentiations not present in pluripotent stem cells naturally. Adult stem cells are the easiest to attain and offer minimal ethical issues however due to their lack of potency their isn’t much research that can be done and would be incredibly difficult to get any promising results from especially on the topic of regrowth of limbs, and would almost certainly take much longer to get these results.

Due to moral issues with attaining these stem cells many people disagree with their use and believe that we should not due to their being no necessity to having the capability of regrowing limbs, which has been shown with us adapting through prosthetics which are being improved every year. People also disagree due to morals and religious beliefs which gives cause to people wanting this research to stop altogether. During the entirety of this essay, I will be going over these points, arguing their validity and in the end whether I believe we should continue this research and regrow limbs.

For

Stem cell research, as previously mentioned, is the main and most likely idea to attain regrowth of limbs due to using the idea of biomimicry and copying how specific animals are capable of regrowing their limbs through the use of pluripotent stem cells. Therefore, researchers are attempting to find a way to recreate what the regeneration blastemas can make through many different experiments on many different animals with this regenerative ability to hopefully discover regeneration. But why is attaining limb regrowth important? This is because the number of amputees globally is increasing. Right now in the USA, there are around 2.1 million amputees with at least one limb missing which is equal to a total of 0.63% of the population. Additionally, it is predicted that by 2050 this number will increase up to 0.96%. This increasing number is due to the increased number of people that go through an amputation each year which right now is around 185,000 people, with the most common amputation being a below-the-knee amputation, covering around 71% of all dysvascular amputations. Those who undergo these amputations in the USA will then have a total lifetime healthcare cost of around $510,000 on average which is around $150,000 more than the total lifetime cost of somebody without limb loss. This additional cost, which is often very sudden, can cause many people issues as many in the US already struggle with health care expenses so with the addition to the money needed to pay for the care and treatment of being amputated, many people can be put into great debt. The effects of becoming an amputee aren't just financial, it can also greatly psychologically affect people. This is the case as according to research, around 30% of people who suffer from loss of a limb also suffer from depression, anxiety, or both of these compared to the entire population whom only around 18% of having as a whole. This research shows how the loss of a limb can not only put you in a state of financial issues and also then statistically increases your chances of attaining a psychological condition such as depression and anxiety on average by 12%, which is a large margin. So, by creating a means to reduce this physiological and possibly even one-day financial cost would be highly beneficial. This would be done through the eventual recreation of their limb, which would likely be done through stem cells. Using stem cells would create a near identical limb to the original, or in the case of people who suffer from congenital amputation they would be able to witness an entirely new limb, as they would have been born missing a certain limb. Whilst many people then go and get prosthetics to counteract this loss of a limb, they can often be bulky and stand out which, especially in the case of children, can cause bullying and feelings of isolation and body image issues which many already suffer from and affects girls a great deal already, these sorts of things in many cases can cause children to leave their current schools and develop psychological issues. During an interview done with three different amputee women, the group who conducted the interview asked them several questions such as about the issues they faced growing up to which they 2 of them responded about being picked on and how their childhood experiences caused them lots of discomfort and hard experiences which caused them emotional issues. However, the other one responded about how shocked people were due to her absence of depression or crying, but stated that the only problem for her was that she “just wanted to get rid of the pain”. This lead me to think about how amputees don’t just get affected psychologically but also often have lingering pain throughout their entire life. The main example of this would be residual limb pain. This is a pain that originates at the remaining part of the limb. It can be created by a multitude of conditions related to the surgery undertaken or it can be caused by conditions that affected you prior to the amputation.

This mostly only occurs on amputees who used to have limbs and so doesn’t affect people with congenital amputation due to this lack of a limb being caused naturally. But, for those who undergo any sort of surgery to attain their amputation would be at risk of suffering from this, as this limb pain can be caused by a multitude of things including: surgical trauma, which is where the bone of the residual limb was not properly trimmed, neuromas, which is a collection of nerve endings which are very sensitive, heterotrophic bone, which is when an excess bone is formed around the bottom of the amputated limb and finally entrapment of the nerve, which is where there are sensitive nerves concentrated in the scar tissue. Due to any of these causes, a person's life can be made miserable through constant pain and suffering. So, due to this for many, I believe that the chance to regrow a lost limb would be a dream come true for them as it would prevent this paint from occurring or remaining and would then give them the added bonus of fitting in more in society and reducing the level of bullying, which would then decrease their depression, anxiety and other psychological issues which could have been caused through this process.

So far, stem cells have been unable to achieve regrowth in humans, however, this doesn’t mean stem cell research hasn’t come remarkably far. As of now stem cells are mostly just used for curing hematological malignancies which are “cancers that begin in the cells of blood-forming tissue (e.g., bone marrow), or in the cells of the immune system”. So whilst they are useful in achieving this, it’s still essential that the cancer is found early on and not let to get to a later stage of development. A few years ago, the department of defense joined the field of regenerative medicine receiving a massive total of around $265 million whilst including $80 million in public and private funds and around $100 million in NIH grants held by the researchers. With all this funding they were aiming to use embryonic stem cells to achieve “regrowing severed fingers, recreating shattered bones, reconstructing mutilated faces and covering burn victims with genetically matched skin”. This shows how much funding went into for these specific uses of stem cell research, and yet for the past few years, they still haven’t achieved any of their main aims fully despite estimating that it would only take up to 5 years to discover a means for this level of regrowth. However, it was through this research that we were able to figure out a means to help to treat cancers, especially for the case of hematological malignancies to which this research was invaluable. This, to me shows the complexity of this stem cell research and how it will take us more time to get where we aim to be, but we are still making huge strides towards improvement on the way.

Against

I am then going to talk to about the negatives of using stem cells, mostly focusing on the ethical issues and giving examples of how they have affected people, but I also want to write down the religious issues with it and how it goes against certain groups beliefs. Then I want to talk about the alternatives and what we are currently doing to counteract having a loss of a limb, focussing mostly on the different prosthetics and why each would be used.

Whilst the pros of regrowing limbs, many people disagree with the methods of attaining it. This can be due to a multitude of reasons including religion and morals with many people believing that these should cause stem cell research to end all together. I believe that the biggest reason as to why people oppose stem cell research is due to the method of collection of embryonic stem cells. The reason for this is that in order to collect embryonic stem cells, the human embryo will become destroyed in the end, of which could have become a new life. Both certain religious people and people with similar moral beliefs to that of abortions are against stem cell research because of this. For catholic Christians and people with similar moralities, they believe that human life begins at conception, which causes the research to be the equivilant to murder due to the result of the death of the embryos. This claim is further supported by the late Pope John Paul II who stated in his 1995 encyclical, The Gospel of Life “Human embryos obtained in vitro are human beings and are subjects with rights; their dignity and right to life must be respected from the first moment of their existence”.

Bibliography

1. Americans for cures. What are the different kinds of stem cells? [online] Available at: https://americansforcures.org/stem-cells/what-are-the-different-kinds-of-stem-cells/
2. Murnaghan I, (8 Nov 2019) , New Harvesting Techniques [online] Explore Stem Cells Available at: http://www.explorestemcells.co.uk/newharvestingtechniques.html
3. MITK12Videos, (2015). Why Can We Regrow A Liver(But Not A Limb)? [Youtube] Available at: https://www.youtube.com/watch?v=erMCADOJcHk
4. Chong, I. (2006) Investigations Document Still More Problems for Stem Cell Researchers. Science, [online]. New Series, Vol. 311(No. 5762) pp. 754-755. Available at: https://www.jstor.org/stable/3843577?Search=yes&resultItemClick=true&searchText=%22Stem+cell+researchers%22&searchUri=%2Faction%2FdoBasicSearch%3FQuery%3D%25E2%2580%259CStem%2Bcell%2Bresearchers%25E2%2580%259D&ab_segments=0%2Fbasic_SYC-4631%2Ftest&refreqid=search%3A2c9129100d89b7f66174207fa1e325b1&seq=1#metadata_info_tab_contents
5. BioTech Possibilities (2019), Here Are a Few Surprising Limb Loss Statistics [online] Available at: https://biotechpossibilities.com/here-are-a-few-surprising-limb-loss-statistics/
6. Young E. (2009), Growing Up With Limb Loss, Amputee Coalition [online] Volume 19 · Issue 2 Available at: https://www.amputee-coalition.org/resources/growing-up-with-limb-loss/
7. Amputee Coalition, Pain Management of Residual Limb Pain [online] Available at: https://www.amputee-coalition.org/limb-loss-resource-center/resources-for-pain-management/management-of-residual-limb-pain/
8. Pritha Ray, Abhijit De and Aparna Khanna (2015), Application of Adult Stem Cells in Medicine, Stem Cells International [online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539501/
9. Science Direct, Hematologic Malignancy [online] Available at: https://www.sciencedirect.com/topics/medicine-and-dentistry/hematologic-malignancy
10. Holden C. (2008), Rebuilding the Injured Warrior, Science [online], New Series, Vol. 320, No. 5875 (Apr. 25, 2008), p. 437 (1 page) Available at: https://www.jstor.org/stable/20055055?Search=yes&resultItemClick=true&searchText=%28Regrowing&searchText=arms%29&searchUri=%2Faction%2FdoBasicSearch%3FQuery%3D%2528Regrowing%2Barms%2529&ab_segments=0%2Fbasic_SYC-4631%2Ftest&refreqid=search%3Aac476357b50f8952f9238fac527267dc&seq=1#metadata_info_tab_contents
11. Pew Research Center (2008), Stem Cell Research at the Crossroads of Religion and Politics [online] Available at: https://www.pewforum.org/2008/07/17/stem-cell-research-at-the-crossroads-of-religion-and-politics/