The University of Southampton

Tag: Stem Cells

iPSC’s: The Universal Cure to Human Disease?

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Induced Pluripotent Stem Cells (iPSC’s) are a type of stem cell that can be used as a replacement for embryonic stem cells in the research and treatment of human disease. As a Biomedical Science student who has an interest in pharmacology and drug therapies, I believe iPSC’s will lessen our reliance on conventional drugs by targeting diseases at their root cause: cellular dysfunction. The ability to replace damaged cells with new ones provides a novel mechanism for treating diseases, but is it the one size fits all solution to all of humanities ailments?

Introduction

iPSC’s are derived from normal human cells, such as fibroblasts, and are cultured with pluripotency inducing factors such as Oct4/Klf1/Sox2, which are delivered to the cells within a viral vector. This gives the cells the properties of potency and self-renewal that are indicative of pluripotent stem cells. They can then be differentiated into tissues that can be used for drug screening in the lab or inserted into the patient in order to replace missing or damaged cells/tissues. These cells are similar in properties to embryonic stem cells (ESC’s), which are the staple type of stem cell used in regenerative medicine. However due to ethical concerns over the use of ESCs from failed IVF cycles, iPSC’s offer a more ethically sound alternative to be used in regenerative medicine.

What are iPSCs? | I Peace, Inc | Regenerative medicine and drug discovery through iPSCs

A Simplified diagram of the conversion of somatic cells into iPSC’s

The potential

iPSC’s have the potential to cure a wide range of diseases, from replacing β-cells in the pancreas in Type 1 Diabetes to the replacement of dopaminergic neurones in the brain in Parkinson’s Disease. Diabetes is important to myself as I have many family members who suffer from Type 1 and Type 2 Diabetes, and from interviews with them I found that they struggle with the insulin injection as well as the constant measuring of blood glucose level via a finger prick test. So as a future medical researcher, iPSC’s excite me, as they open an avenue to where diabetes can be cured by replacement of lost β-cells, leading to an eradication of the hampered quality of life people with diabetes must undergo.

Explores the role of stem cells in diabetes treatment.

Explores the role of stem cells in diabetes treatment.

The Issues: Ethical

iPSC’s and their side effects do not line up with Aristotle’s view of ethics as a virtue; as they would not be classified as a high-quality treatment due to their tendency to form tumours, therefore its poor ability to carry out its regenerative function would prove them to not be an effective treatment option. As well as this, in my opinion the use of these cells in a widespread manner may lead to opening pandoras box, where people will look to improve the function of their healthy tissue instead of treating diseased tissue. For example, certain factors may be able to be added to iPSC’s in order to produce muscle tissue with an abnormally high amount of Type IIx muscle fibres, and once transplanted giving them a predisposition to being a successful power athlete such as a sprinter. This in turn will unlock the door to ‘perfect’ humans, a dystopian world with a socioeconomic divide between people who can afford to improve their bodies and those who cannot.

Conclusion

To conclude, iPSC’s are very promising and have a lot of potential for use in regenerative medicine. However, the technology still needs refining and legislations need to be put in place to ensure the technology is not applied outside of disease therapy.

New Stealthy Stem Cells?

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Developments in new gene editing techniques provides stem cells with the ability to bypass the immune system offering new applications in cell replacement therapy.

There are more than 10 million people worldwide currently living with Parkinson’s disease and 3 million people recorded to be living with type 1 diabetes globally in 2017. Both of these chronic diseases are currently incurable and require regular medication and treatment to control. Due to their life-long impacts, many people can relate to the implications these diseases have on both the individuals diagnosed and the family members or friends of the individuals. The negative effects can be physical, mental, social or financial and often a collection of them all.

So if there was a possible solution would you take it?

Research has suggested a new strategy that could provide an endless supply of replacement body parts for individuals suffering from debilitating disorders and diseases. Scientists can now grow stem cells in the laboratory and engineer them into specialised cell types. Which can eventually be transplanted into humans and potentially cure diseases, once believed to be incurable. For Parkinson’s disease this could mean cultivating neurones to combat the progressive damage made by the disease over the years to different parts of the brain, or for type 1 diabetes insulin-producing pancreatic cells could completely reverse the effects of the disease and lastly heart muscle cells to could be transplanted to enhance cardiac function. These are just a few examples of the life-changing effects this new treatment could have.

In genetically modified mice predisposed to autoimmune diabetes, pancreatic cells undergo infiltration and destruction by “killer” T-cells, leading to a decline in insulin production (pictured on the left). However, administration of MOTS-c injections mitigated T-cell infiltration, consequently averting disease onset (pictured on the right).

Credit: Newcomb (2021)

How this is possible…

Utilising gene-editing techniques like CRISPR-Cas systems, stem cells can be manipulated to possess immune-evading traits, effectively bypassing recognition mechanisms. Moreover, these engineered cells can integrate fail-safe features to guarantee cells can be eliminated in the case of unforeseen issues. Consequently, such ‘stealth’ cells hold promise to support various cell-replacement therapies.
In most cases, the process starts with the disruption of at least one component of the cell’s major histocompatibility complex (MHC). This complex functions like a molecular identity card, showcasing distinct cellular information fragments that inform the immune system’s T lymphocytes, its frontline defenders, and whether the cell is hostile.
To mitigate potential susceptibility to natural killer cells (NK), certain researchers have suggested the reintroduction of genes encoding particular MHC antigens. These antigens enable the cell to modulate NK cells without eliciting T-cell responses that may induce apoptosis (cell death). NK cells serve as the effector lymphocytes of the innate immune system, tasked with regulating various tumour types and microbial infections to restrict their dissemination and consequent tissue harm. Alternatively, other strategies may involve introducing genes that produce ‘checkpoint’ proteins, specialised molecules aimed at directly suppressing NK cell activity.

Are there any downfalls to this ground-breaking new strategy?

Unfortunately, therapies stemming from stem cells require customisation for each patient, a process that is both time-consuming and costly. Alternatively, these treatments can utilise donor cells; however, due to the tendency of the immune system to reject foreign cells, such ‘allogeneic’ therapies require the administration of immune-suppressing medications alongside treatment. However, this approach escalates the risk of complications like infection and cancer.

Ultimately, the optimal safety strategy, as well as the ideal extent of gene editing required to suppress immune responses, may vary depending on the disease. For instance, pre-made cell therapy for cancer may not require the same design features as one tailored for diabetes, given the differences in the immune system’s response and the distinct risk-benefit considerations for each ailment. In essence, there is no ‘one-size-fits-all’ solution.

With the true test of human trials likely to follow soon the future of this treatment is looking hopeful.

Acknowledgements:

Dolgin, E. (2024). Stealthy Stem Cells to Treat Disease. Nature. [online] doi:https://doi.org/10.1038/d41586-024-00590-y.

Green, A. (2008). Descriptive Epidemiology of Type 1 Diabetes in Youth: Incidence, Mortality, Prevalence, and Secular Trends. Endocrine Research, 33(1-2), pp.1–15. doi:https://doi.org/10.1080/07435800802079924.

Newcomb, B. (2021). Small Protein Protects Pancreatic Cells in Model of Type 1 Diabetes. [online] USC Leonard Davis School of Gerontology. Available at: https://gero.usc.edu/2021/08/12/mots-c-mitochondria-type-1-diabetes/ [Accessed 5 Mar. 2024].

Parkinson’s Foundation (2024). Statistics | Parkinson’s Foundation. [online] www.parkinson.org. Available at: https://www.parkinson.org/understanding-parkinsons/statistics#:~:text=Parkinson.

Vivier, E., Tomasello, E., Baratin, M., Walzer, T. and Ugolini, S. (2008). Functions of Natural Killer Cells. Nature Immunology, 9(5), pp.503–510. doi:https://doi.org/10.1038/ni1582.