The University of Southampton

Author: Danica Nuqui

Minimally Invasive Knee Replacement Surgery?

Posted on by

Total knee replacement surgery (TKRS) involves the removal of damaged and painful areas of the knee joint and replace it with specialised metal and plastic. A lecture by Dr. Nick Evans reflected on the disadvantages and problems with prostheses. He highlighted that internal prostheses comes with many issues, such a finite lifespan and can only be used for certain problems. 

With this surgery comes many serious complications of joint replacement surgery, and these include: wound infection, blood clotting, malfunction of prosthesis or nerve injury. Upon reading these statistics, it made me feel inclined to research and find alternative, less invasive treatments for those in need of knee replacements.

image of a normal knee vs an arthritic knee

Knee osteoarthritis is a degenerative joint disease that breaks down joint cartilage and mostly affects middle-aged and older adults. It is the most common reason for knee replacement surgery, with 4.7 million estimated to have undergone TKRS in 2010. Mobility is significantly reduced and patients often experience constant pain even when resting. It is evident that this type of knee damage can be a burden for those suffering from it and I understand why people consider surgery to resolve it.

Common current treatment options

The most common surgical treatment for knee osteoarthritis is a cemented prosthesis. This is the process in which a layer of bone cement is placed in between the patient’s natural bone and prosthetic joint component. The advantages of cemented prostheses is that bone cement is fast-drying (10 minutes) upon application so there is confidence that the prosthetic is firmly in place, as well as early pain relief. However, with all surgery options, there are drawbacks. These include irritation of surrounding soft tissues and inflammation as a result of cement debris, and breakdown of cement can cause loose artificial joints in which patients would need to undergo another surgery. So if this current treatment for knee replacement is too invasive for the patient, then what other treatments are available that come with less serious complications and disadvantages?

a cemented prosthesis in the knee

Other treatment options

Something that shocked me was that there are many different alternative treatments for knee replacements. Here are some that particularly stood out to me, and ones that I would consider if I suffered from knee osteoarthritis. 

Cartilage regeneration is the replacement of cartilage instead of the entire joint for joints with limited arthritis. Autologous chondrocyte implantation (ACI) is a procedure that involves taking a sample of the patient’s cartilage cells, growing them in the lab and surgically replanting them into the knee. This may be a treatment offered for those effected by cartilage loss, with this implantation producing good/excellent results in 90% of patients with femoral condylecartilage loss (Minas and Chiu 2000). This may be promising for those who are looking at alternative treatment plans before fully committing to TKRS.

diagram of the process of ACI

Current research has revolutionised TKRS with a new technique called the minimally invasive total knee replacement (MITKR). This involves smaller incisions than regular TKRS, which requires less muscle dissection and results in quicker and less painful recovery. This approach is said to have potential for dramatically reducing pain for muscles and tendons that have previously been cut during the standard TKRS. These benefits for this surgery has paved the way for less complications like less blood loss during surgery, and increased range of motion sooner after surgery. Overall, this promising and innovative minimally invasive total knee surgery has the potential to be the more commonly used treatment over others like cement prostheses. Video of this procedure can be found here.

Concluding thoughts

As I researched more into the field of alternate knee replacement treatments, I didn’t think that there were this many other forms available. I believe that it is beneficial for those in need of knee replacements to have many treatments available, especially for those that are unsure about fully committing to TKRS due to its invasive nature and serious complications. I personally would choose MITKR over the standard knee replacement surgery if I suffered from knee osteoarthritis, with its promising benefits and minimally invasive nature. With developing surgical treatments, such as MITKR, I will definitely keep up to date on the current and emerging treatments for knee replacements to further enrich my knowledge.

Can Human Embryonic Stem Cells (hES) Be Used to Cure Diabetes?

Posted on by

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.

pancreatic β cells

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.

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

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.

six-stage SC-β cell differentiation protocol (Hogrebe et al. 2021)

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

Can Stem Cells Cure HIV?

Posted on by

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.