Type 1 diabetes is a prevalent chronic illness with 1.4 million new cases in the USA per year. (ADA). It is a product of an insufficiency of insulin, caused by the autoimmune destruction of the insulin-secreting pancreatic β-cells. There is no current cure for Type 1 diabetes, however, there are a number of treatments to help cope with it.

Islets of Langerhans are cells from human donors in the pancreas that secrete insulin and glucose and can continually control blood sugar levels when implanted in the liver. Islet transplantation for diabetes has shown to be less invasive and result in fewer complications in comparison to traditional transplantations.

One potential cure for Type 1 diabetes is human embryonic stem cells (hES), which are cells that have the ability to efficiently and rapidly differentiate and are functionally similar to adult human islets. This suggests that hES cells may be a  renewable supply of human β-cells that can aid to the development of cell therapy for diabetes (Kroon et al. 2008). A limitation in this domain is that there is a scarcity of donor tissue (Champeris Tsaniras and Jones, 2010), which can restrict the use of such therapies. This reflects the need for more donors to help treat those with this chronic illness.

In more recent literature, protocols have been created/improved to drive human pluripotent stem cell–derived pancreatic β cell growth (SC-β cells) through the stages of its development (definitive endoderm, primitive gut tube, pancreatic progenitors, endocrine, and β cells). Hogrebe et al. (2021) postulated the importance of the influence of microenvironment and cytoskeletal signalling on endocrine induction (both of which can influence the generation of these cells) that generate highly functional SC-β cells.

This not only simplifies differentiation methodology, but also improves outcomes for multiple cell lines. This is advantageous as cell lines have a longer life span, proliferate more quickly and are easily manipulated. These are important for complex tissues and allow for better examinations of alterations in structure, genetic makeup, and biology of the cell. Using this new information, Hogrebe et al. (2021) created the six-stage SC-β cell differentiation protocol for generating highly functional SC-β cells. This protocol recreates stages of embryonic development to achieve high SC-β cells maturity and differentiation efficiency. A limitation to note, however, is that this multi-stage process takes 5 weeks to complete, which can create possible problems that affect the successful generation of stage SC-β cells. Despite this, this paper has lay the groundwork for effectively generating stage SC-β cells from cell lines that didn’t work for other protocols. Overall, this has posed a positive impact on this research field and has pathed the way for improved protocols for cell generation and potential cures for Type 1 diabetes.

Final considerations:

Earlier in the module, my interest was captured when the lecturer mentioned stem cells and diabetes in week 2. With family attachments to diabetes, I felt an appeal to research further into this field. I never fully understood the burden diabetes can have on an individual, and I feel as if others don’t quite understand either. Therefore, reading more into this literature has only enriched my knowledge further and given me the opportunity to better understand the struggle.

One aspect that sparked my interest when doing my research is that there are developments for potential cures, which I didn’t realise there could be one. With advancing technology anything is clearly possible!

My take home message from doing this research is to encourage more people to donate donor tissue to help those with diabetes and that bioengineering technology and developments are only growing, which gives hope to those currently suffering with this chronic illness.

Reference list:

Champeris Tsaniras, S., & Jones, P. M. (2010). Generating pancreatic β-cells from embryonic stem cells by manipulating signaling pathways, Journal of Endocrinology, 206(1), 13-26. Retrieved Mar 6, 2023, from https://joe.bioscientifica.com/view/journals/joe/206/1/13.xml

Hogrebe, N.J., Maxwell, K.G., Augsornworawat, P. et al. Generation of insulin-producing pancreatic β cells from multiple human stem cell lines. Nat Protoc 16, 4109–4143 (2021). https://doi.org/10.1038/s41596-021-00560-y

https://diabetes.org/about-us/statistics/about-diabetes#sthash.F8fRkPqd.dpuf#:~:text=Prevalence%3A%20In%202015%2C%2030.3%20million%20Americans%2C%20or%209.4%25,American%20children%20and%20adults%20have%20type%201%20diabetes. accessed 6th March, 2023.

Kroon, E. et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat. Biotechnol. 26, 443–452 (2008).

Xin-Xin Yu, Cheng-Ran Xu; Understanding generation and regeneration of pancreatic β cells from a single-cell perspective. Development 1 April 2020; 147 (7): dev179051. doi: https://doi.org/10.1242/dev.179051

“The wrongs which we seek to condemn and punish have been so calculated, so malignant, and so devastating, that civilization cannot tolerate their being ignored, because it cannot survive their being repeated.”

Nuremberg Trials

During the last lecture of Engineering Replacement Body Parts, the main topic was bioethics. Although I was never introduced to this topic before, in high school I had already heard about the “Nuremberg Trials”, and their importance in condemning people responsible for such atrocities during World War II. This is the reason why I decided to write this post about this historical event that completely changed our views about scientific progress and research. 

Crimes against humanity

Crimes against humanity refer to specific crimes against a large-scale attack targeting civilians, regardless of their nationality. These can include persecution, murder, sexual violence, enslavement, torture, enforced disappearance, etc. Unlike genocide, crimes are not necessarily committed against a specific national, ethnical, racial or religious group. These crimes can also be committed in peacetime by legal State policies as well as non-State armed groups or paramilitary forces. 

Since the 1945 Nuremberg Charter, the list of crimes against humanity expanded via diverse international treaties, such as the Statute of the International Criminal Tribunal for the former Yugoslavia (1993), the Statute of the International Tribunal for Rwanda (1994) and the Rome Statute of the International Criminal Court (1998). The Rome Statute is the most recent and expansive list of specific acts that may be considered against humanity.

Video introducing the Nuremberg Trials

18th October 1945

The International Military Tribunal (IMT) was composed of both Allied countries and representatives of Nazi-occupied countries and aimed at punishing the leaders and army of a regime. This was the first time in history. 22 Nazi Germany’s military, economic and political leaders were brought to trial in Nuremberg for crimes against peace, war crimes, and crimes against humanity. The tribunal delivered its judgement against the Nazi leaders on 30th September and 1st October 1946: 12 were sentenced to death, 3 to life imprisonment, 4 to imprisonment ranging from 10 to 20 years, and 3 were acquitted.

Subsequent Nuremberg Proceedings

Subsequent Nuremberg Proceedings were trials to determine the guilt for crimes against peace, war crimes, and crimes against humanity of defendants who represented many parts of German society, from jurists and politicians to businessmen, physicians, army officers and collaborators.

These trials included 23 leading German physicians and administrators who were accused of human experimentation utilising thousands of concentration camp prisoners without their consent or were involved in the Euthanasia Program. This programme aimed at systematically killing those they considered “unworthy of life” due to severe psychiatric, neurological, or physical disabilities. On 20th August 1947, after almost 140 days of proceedings, including the testimony of 85 witnesses and around 1,500 documents, the judges found 16 physicians guilty, and 7 were sentenced to death. 

I already knew about the Euthanasia Programme due to a school journey in Germany and Austria aimed at “experiencing” the journey of survivors of WWII. In this journey, I also visited an actual centre that was used during the Euthanasia Programme to exterminate all German and Austrian children with severe neurological disorders and autism: the “Hartheim Castle”. I still remember the net contrast between the appealing aspect of that castle and the very dark atmosphere inside.

In the ground floor of this castle, there is a very impressive memorial that was made after Americans occupied that place at the end of the war. This memorial is a continuous screen positioned along the walls and in the centre of a room. This screen quotes names of all people killed there, at least the ones we have memories of. These names were written very close to each other with a very small size, and still occupied an entire room. This view is still so vivid in memory and continues to impress me.  

While researching more about “crimes against humanity”, I realised that the Nuremberg code is not the only one that codifies specifically for crimes against humanity but there are more recent codes I had never heard of! Moreover, I had no idea about the existence of so many different types of crimes that can be considered against humanity. I thought that the only one was basically the extermination of part of society with specific traits or ethnicity (e.g., extermination of black people or Jewish). This proves that it is never wrong to reiterate such important ethical concepts. I felt also shocked by the very small number of people actually sentenced for those crimes, compared to the real number of people that should be held responsible. 

In conclusion, it is still incredible to me how the Nuremberg Trials, held more than 70 years ago, can still affect so much our scientific progress and research. I believe that this knowledge is essential for me to become a good biomedical scientist. I will always keep in mind this determining historical event while designing my own experiments as well as reviewing other scientists’ papers to avoid committing the errors of the past. That way, I can positively contribute to the scientific community in an ethical and respectful way. 

References

1. United States Holocaust Memorial Museum, “The Nuremberg Trials”: https://www.ushmm.org/collections/bibliography/the-nuremberg-trials

2. TRIAL International, “Crimes against humanity”:

Recently I read a news article about a man called Adam Castillejo who was cured from HIV by a stem cell transplant he received for a cancer that he had and is still virus free 30 months after stopping HIV medication! This compelled me to research further into this, as I personally would have never made this link. 

Stem cells are known for their ability to change into specialised cells that later develop to become blood cells, bones, and all human organs. Stem cells are cells produced by bone marrow and utilised to treat many medical diseases and conditions with their potential to repair, replace, restore and regenerate cells. They are most commonly used to replace damaged cells in cancer patients to fight such diseases.

I’m sure almost everyone has heard of HIV, but just to recap, HIV stands for a Human Immunodeficiency Virus that weakens people’s defence against infections and is most prevalent in male homosexual contact. At the end of 2018, it was found that an estimate of 1.2 million Americanshad HIV, with 76% of those being men. To shock you even more, HIV is top 15 for the leading causes of death globally in 2016. Now with that background knowledge of both, have you ever thought that stem cells can cure HIV? 

I particularly have never put two and two together, however, with recent news, it is stated that there are currently five people cured of HIV – most of them cured as a result of stem cell transplants. Current research has illustrated that stem cell transplants stop the HIV virus being able to replicate by replacing the patient’s damaged immune cells with specialised donor immune cells that resist the HIV infection. However, this treatment is aggressive and primarily used for cancer patients, and health professionals suggest not using this therapy for those on successful anti-retroviral treatment for HIV. 

The primary goal for treating HIV is the clearance of the virus from the body through augmentation of immune responses. For those who don’t know, CCR5 is a receptor that HIV uses to enter cells in the body. Those who are resistant to HIV appear to have two mutated copies of the CCR5 receptor, which means that the virus cannot penetrate the cells. Researchers have suggested the use of gene therapy (gene modification) to target the CCR5 receptor in HIV patients. Researchers are currently developing strategies to cure HIV, with the idea that stem cells are resistant to the virus, the cells produce lower amounts of infectious virus, or the cells specifically target the immune response against the virus.

Previous clinical trials have shown new advances in these stem cell-based approaches to curing HIV, with onein particular demonstrating that large-scale gene therapy trials can be done in a conventional and reproducible way. This efficient way to produce these specialised stem cells is ground-breaking and only further paves the way for a promising cure!

For me, I would have never thought stem cells to be the cure for HIV, or even the fact that this disease is curable with, although very few, survivors. I feel that this topic is very underdiscussed, especially since reading into this field, I have only further enriched my knowledge. New and current emerging information on HIV and gene therapy has laid the groundwork for the potential development of a cure for HIV, however, long-term follow-up is needed.

Manuel is only four-year-old when he is diagnosed with acute myeloid leukemia. Manuel is an Italian boy who survived cancer thanks to a stem cell transfusion from a Spanish donor and ten years after the transplantation, his family decided to visit the center where the stem cells that gave Manuel a second life originated. A moving moment for Mother Simona, who received a token of love in the form of a contribution that she, too, decided to make in 2007, with the birth of her second child.

For about 35 years now, in a completely non-invasive and safe way, it has been possible to donate mother’s umbilical cord from which special cells are taken, stored, and used to treat diseases of people from anywhere in the world. These “special cells” are called Hematopoietic stem cells and can change into any sort of blood cell and can be utilized for transplants that help cure diseases such as blood problems, immunological deficiencies, metabolic diseases, and some forms of malignancies. At the end of the birth, after the cut, about 1 liter of blood is taken through a puncture to the umbilical cord. The sample obtained is sent to the collection bank, assessed if suitable and then frozen pending use. Banking cord blood has been compared to a “biological insurance policy” and there are two types of banks to go to: private and public, but which is the best solution to ensure safety for your child?

The choice should always lean towards donation and the reason is primarily scientific as there is no scientific evidence that private conservation is useful in the treatment of various diseases treatable through transplantation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1601996/). When a mother decides to donate to a private bank, the treatment is carried out for a fee and the cells are kept for a period of about 20 years, after which, by paying a further amount, the storage time can be extended. The cells are accessible only to the patient from whom they were taken or from a family member, with the intention of treating a possible future disease. The point is that in the case of oncological or genetic diseases, one’s cord blood cells could already be carriers of those genetic “defects” that have led to the disease. In these cases, the persistence of diseased cells in the product which is reinfused involves the risk of the disease reappearing. The only justified case for turning to private banks could be the presence of a hereditary risk, which can be treated with autologous stem cells. On the other side, donating to a public institution is free and guarantees a second life to a patient with a match who really needs it. If every mother decided to turn to public bodies, the material kept in the banks would increase and there would be much more chances that every applicant could find a compatible donor.

Donate is life, love and a responsible gesture towards the world and everyone should be aware of it.

The video below shows the process of how to harvest stem cells from umbilical cord blood and keep them in the bank