The University of Southampton

Author: Madeline Heenan

The Ideal Stem Cell

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I have had an interest in stem cells since beginning my degree. Following a lecture on stem cells I attended, I found myself more curious about their applications and how they are attained. I was told umbilical cords are a good source of embryonic stem cells which are pluripotent (the most useful!) and my mum in fact told me she left my umbilical cord and placenta with the nurses to be used to harvest stem cells for those who need it. These cells are typically used in cancer, immune deficiency and genetic disease treatments. I found this super fascinating and I was proud that I, somewhat, contributed to that.

Stem Cells in Therapies

Stem cells used in disease treatment are already naturally lineage restricted, such as the transplantation of haematopoietic stem cells for blood cancers as discussed in our lecture. At the same time, some therapies may benefit from more undifferentiated stem cells, like human embryonic stem cells (hESCs) or potentially more ethically attained induced pluripotent stem cells (iPSCs). The limitations of using these pluripotent cells is that they result in the creation of a heterogeneous mixture including undesired cells, which as discussed in an article I saw, are difficult to expand and maintain in vitro, making in vivo applications more difficult. Further advantages and disadvantages of these cells are shown in the following image:

Scientists have weighed up these pros and cons and are now creating a different kind of stem cell that is much more specific for those cells that don’t have endogenous multipotent stem cells already.

Parkinson’s and Stem Cells

To investigate this further, I looked specifically at the use of lineage restricted stem cells in the treatment of Parkinson’s Disease (PD) which I have a personal interest in. For context, PD is a neurodegenerative disease characterised by progressively worse tremors and slow movements. It is unclear its direct cause, but stem cells are a trending mode of treatment. Scientists use pluripotent stem cells and treat them to become dopamine-producing neurones. Following legal guidelines from the Human Fertilisation and Embryology Act 1990, researchers have used embryonic cells from IVF programmes before 14 days of embryonic age. They also used iPSC since their discovery. But, these do not cure Parkinson’s. So what can be done to try to cure this disease?

An article I saw on researching this issue discusses their success with the use of lineage-restricted undifferentiated stem cells, from pluripotent cells. They found that 69% of these cells differentiated into the desired cell type (dopamine releasing neurones), a significant number compared to only 25% of hESC. This is a great result! They have kickstarted the research into lineage-restricted stem cells for PD (and I’m sure it has inspired people to try the method for other diseases )and emphasises how stem cell engineering is becoming a vital tool and could lead to potential cures for various diseases. I learnt there is more to stem cells than just pluripotency and they are more intricate than I had thought.

My final thoughts

I believe stem cell engineering and the potential around the creation of the ‘ideal stem cell’ is something that more people need to be educated on. There are still unresolved ethical questions but only through more education and understanding will we find the best ways to manage all expectations. It is exciting to think about the future applications of stem cells, what discoveries will be made and the overall benefits to all from this work.

Metal implants: Good or Bad?

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A metal implant is a biomaterial commonly used in orthopaedic surgery to help bones heal, or replace them entirely. Alloys are most typically used. They are designed to be non-corrosive, hard and durable – everything needed from the implant. In the photo below, the hip replacement one is probably the most recognisable, which 71,000 people in the UK have.

https://www.sciencedirect.com/science/article/abs/pii/S1286011518302479

Deciding on the make of the implant is very important. An article I read discussed how doctors need to consider what metals the patient has already been exposed to and what metals will be problematic, however a rejection can occur without any previous hypersensitivity. It suggests management strategies in the case the implant causes immune rejection. It states “Successful medical management with oral atropine sulphate has been reported in a patient with titanium pacemaker as well as with oral corticosteroids in a patient with titanium bioprosthesis for a spinal fracture”. This highlighted the importance of figuring out what metal to use in an implant, something I had not considered in much detail. The following link describes some types of implants: https://youtu.be/FfRZuNaKGdU?si=dT2X0tKhaC6ayGcF.

Image showing examples of types of implants

Patient’s reaction to the metal implantation varies dramatically. Some people show no rejection of the metal, others can show hypersensitivity to the metal and their body actually rejects it, causing intense pain and inflammation for the individual, potentially to the point that the implant has to be removed, but then what do they do to fix the issue?

Fixing the issue, but not completely…

Something which is used to reduce the risk of implants failing is covalently immobilising biomolecules onto the metal surface. An article in the Biomedical Engineering Advances journal believes that using a covalently attached immobilised biomolecule or not is a main determinant in the efficiency of the implant. Of course, this depends on what biomolecules are used and the patient’s individual differences, everyone’s immune system will react differently to the same thing. An example of an immobilised biomolecule is fibronectin, this forms an amide bond with the metal surface, others investigate Arg-Gly-Asp-containing peptides and ubiquitin.

A downside to the use of metal implants is stress shielding. This occurs when the bone density decreases as the stress load on the bone is reduced, due to the presence of the implant. This is a major issue for implants that will not be lifelong (a lot of implants – they do not last forever). This issue may not be apparent until after the metal implant is removed, such as after a severe femur break and the leg is significantly weaker and smaller.

So, what happens when metal implants do fail?

Well, in the UK, patients who’s implants fail, or cause harm, are able to bring legal action against the manufacturers and they are held accountable. The Nuffield Council on Bioethics in June of 2019 estimates ‘over 300 UK patients whose hip implants had failed brought legal action against the manufacturer under the Consumer Protection Act 1987’.

My opinion?

I believe there are lots of ethical considerations that need to be discussed at greater length. Since metal implants have lots of uncertainty surrounding their lifetimes and consequences (as most of it has not yet been seen) it makes it difficult for patients and doctors to make the correct decision, however this does not mean informed consent is dismissed.

human embryo-like model derived from stem cells

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i recently read an article about the development of stem cells that resemble, roughly, a 2 week old human embryo at the university of Cambridge.

i found this really interesting as the article discusses how many pregnancies are lost within this initial 2 week period for unknown reasons. the engineering of these stem cells into embryo-like cells is important as it now allows for research into why so many embryos fail at this stage.

this is also really useful for investigating the role of developmental genes as they can be genetically modified, something which is difficult to do with the natural embryo. research involving natural embryos is currently illegal after 14 days of development, since the embryo cannot form a twin within this first stage – which i didn’t know so that’s also pretty interesting to me.

the embryos were engineered by over-expressing a transcription factor with embryonic stem cells, which allowed the cells to self-organise into a 3D structure which resembles the post-implantation embryo containing extra-embryonic tissue and a pluripotent epiblast-like cluster.

an example of research already conducted using these cells was the inhibitory role for SOX17 in the specification of anterior hypoblast-like cells.