Stem cells have always been an intriguing topic to me, particularly their therapeutic potential. The idea of being able to use one undifferentiated cell to create whole new organs or body parts is fascinating. After our lecture on stem cells and their therapeutic use, I decided to research the different ways that stem cells are currently being used in medicine, and one case in particular stood out.

The Story

Lesley Calder was diagnosed with acute myeloid leukaemia in 2019. Chemotherapy treatment was unsuccessful for her cancer, and she was left with the only option of a stem cell transplant. Lesley’s three siblings volunteered to be tested, with the slim chance of finding a sibling match (~25%). By some miracle, 2 siblings were full matches and 1 was a half match. Lesley’s sister Annie was chosen to be the donor, and amazingly, Lesley has since made a full recovery.

Using Stem Cells to Treat Cancer

A stem cell is defined as a cell that can self-renew indefinitely and has the capacity to differentiate into many cell types. Their normal function within the body is to replace old, damaged or defective cells to maintain normal tissue function.

Stem cell transplants are used to treat diseases where the bone marrow is damaged or defective, meaning that healthy blood cells can no longer be produced. This is the case in blood cancers (e.g. leukaemia and lymphoma), which primarily affect white blood cells. The loss of blood cells is further exacerbated by intensive cancer treatment (e.g. chemotherapy), which can also damage/destroy healthy cells. The transplantation of stem cells produces new blood cells, and helps to defend against the cancer.

Stem Cell vs. Bone Marrow Transplants

Before this research, I had only heard about bone marrow transplants, and didn’t know stem cell transplants existed, which made me wonder what the difference is. They are essentially the same thing, but differ in the locations where the cells are collected. A stem cell transplant involves collecting stem cells from the bloodstream, which is less invasive than a bone marrow transplant, which involves collecting a person’s bone marrow from within their bone (usually pelvic).

Information from Cancer Research UK says that stem cell transplants are the more common of the two, which I found surprising, considering I hadn’t heard of them. This is because stem cell transplants are: less invasive, easier to perform, have a higher yield of cells and have a quicker blood count recovery.

The Problem & Final Thoughts

Through this research, I have found that over 70% of patients who require a stem cell transplant will not find a compatible donor in their family. Additionally, only 3% of the UK population (and <6% of people in Northern Ireland) are registered to be stem cell donors, making the chances of finding a compatible match even lower. For the majority of patients, like Lesley, a stem cell transplant is their only chance at recovery, and their chances of success are slim.

Lesley’s story prompted her son Max to join the stem cell donor register in hopes of helping others like his mum, and he has already been called upon to donate. By sharing her story, I hope to inspire others to join the register as well, as I will definitely be doing. Anyone aged 17-55 and in good health can sign up here. For more information on stem cell transplants, visit NHS, Cancer Research UK or Leukaemia & Lymphoma Society.

In the UK, 12 million people are affected by hearing loss. 80 million are over the age of 60. Over 900,000 people are severely or profoundly deaf, they are unable to hear any speech. During this module, lectures were given on cochlear implants. My interests on these grew so I decided to do some further research. Cochlear implants are used by 12,000 people in the UK.

How do they work?

A cochlear implant is an electronic device that helps with understanding speech and sensing sounds. There are 4 parts: a microphone, a speech processor, a transmitter and receiver-stimulator and an electrode array. The external speech processor captures sound and converts it into digital signals. The digital signals are sent to the internal receiver-stimulator. The signals are converted into electrical energy which is sent to the electrode array that’s inside the cochlea. The electrode array stimulates the auditory nerve by bypassing damaged hair cells. The auditory nerve transmits signals to the brain. These signals are recognised as sound.

Cochlear Implant

Image of CI

Who gets them?

Cochlear implants are given to those that are congenitally deaf, had an infection associated hearing loss such as measles, trauma associated hearing loss like a head injury, age associated hearing loss and people who do not benefit from hearing aids which can be confirmed by specialised hearing tests.

Benefits and challenges

Cochlear implants are given from 6 months old. This is beneficial for children as they are learning to speak and process language. People will be able to hear speech without reading lips including phone calls. They can hear everyday sounds like the noise made when there is a green man at the traffic light. This improves their safety. Cochlear implants help people develop their speech and pronunciation as they can hear their own voice, improving their communication.

There are a few risks, one is meningitis which can occur after implant surgery. This is prevented by vaccinations beforehand. Another, is the results vary depending on the person. Some people’s hearing significant improves while others don’t receive such satisfaction. Cochlear implants are not an instant fix, time is needed for the brain to get used to how they work.

Technology

Cochlear implants are becoming more advanced with technology. Sound processors can be waterproof meaning children and adults can enjoy swimming and even bathe without worrying about any damages. They can be paired with phones through Bluetooth. Sounds can be wirelessly streamed to the processor. An example is the Nucleus® 8 Sound processor which uses improved technology to sense changes in the environment and can adjust listening settings.

Nucleus® 8 Sound processor

Advanced bionics have a cochlear implant called the HiRes Ultra 3D cochlear implant. This device works with technology, making speech clearer and music with better quality sound.

My opinion

Overall, my thoughts on cochlear implants are that they are amazing as they can help deaf people have a better quality of life. I think that they are accessible in the UK due to the NHS and I was surprised to discover that in the US, they can cost between $50,000-100,000. I was appalled by this as many adults and families with children cannot afford such high prices so they won’t get the benefits of cochlear implants. I love that with technology, the external parts of cochlear implants are smaller so people can participate in sports easily. I’ve been to competitions where I saw children with sound processors and I was happy to see them get the same opportunities and experiences as everyone else. I’m excited to see how cochlear implants will further advance.

The pillars of consideration to providing this surgery involve: beneficence, assessing whether patient’s lives will get better through surgery; non-maleficence, assessing whether risks and potential complications of surgery are worth it (in both short and long term rehabilitation); autonomy, allowing patients evaluation on the most appropriate treatment including informed consent, ensuring patients are comprehensively aware of all courses of treatment and associated risks and benefits; professionalism, in adhering to the highest standards of practise; justice, providing equitable distribution and access to resources regardless of their demographic.

Working in trauma and orthopaedics, I often consider whether prosthetic joint replacement is beneficial in the context of neurodegenerative disorders. I have had difficulty in assisting patients that undergo, for instance, hip replacement and day one post-operatively forget they have undergone the surgery. This can involve mobilising prematurely, potentially jeopardizing the integrity of treatment they have received by dislocating or loosening the implant, delaying the healing process, increasing infection or thromboembolic risks, advertently causing more pain and discomfort. This occurs regularly and can be problematic, with excessive treatment and only DOLS (deprivation of liberty safeguards) to prevent postoperative complications. This can traumatise patients who aren’t aware of their circumstances leading to feeling of emotional discomfort, isolation, and lashing out against those trying to help them.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619389/ – find here a comprehensive pubmed publication into the impact of parkinsons disease on the outcomes of total knee replacement

Despite obligations to provide every patient treatment without discrimination, even with ability to use longer term implants like metal on plastic for patients that expect to benefit from the replacement more (those more mobile) compared to shorter term ceramic prosthetics, how far is the surgery beneficial at all considering the cost and compounding factors to those that will not fully understand or appreciate their treatment and could potentially put it in jeopardy?

https://ebjproliancesurgeons.com/blog/understanding-the-different-types-of-hip-implants/ – find here criteria and description for different joint prosthetic media

Could investment for those with neurodegenerative disorder be better spent on research that can prevent higher incidence of falls, reducing the need for surgery at the source? Could it be better invested in mitigating incidence of falls in care by providing more effective infrastructure in place for this? Could investment be better spent elsewhere where the NHS falls behind for those that may truly understand and appreciate their treatment? This decision operates on a fine line and operates on the boundary of what is ethically right.

Ultimately, I have learnt that our obligations to everyone regardless of their demographic or cognitive state are considered equal. Besides, are we not obliged to those suffering from neurodegenerative disorder that were part of the generation that built and paid for the NHS throughout their lives? However, paradoxically, I would consider higher selectivity in providing such surgical treatments as i believe it could be more beneficial elsewhere in patient outcomes and development would lead to better future outcomes for these patients.

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/414360 – find here a comprehensive study into decision making, procedure, and outcomes of joint surgery in elderly patients with osteoarthritis

With over 3 billion people in the world living with a neurological condition, the pressure for improvements to be made in this field continues to increase. With my grandfather being one of the many people affected, I am personally intrigued in current and future developments to come. Let’s delve into the interdisciplinary approach of biomedicine and engineering for the recovery of neural diseases.

Neurological disorders

The brain and spinal cord are the control centres of the body, sending and receiving sensory and motor information. When this system dysfunctions, it leads to disease. A few examples of neurological disorders are the following:

•Spinal injuries: caused by traumatic damage to the spinal cord, resulting in loss of motor or sensory function, often causing paralysis or impaired mobility.

•Neurodegenerative diseases: include the progressive conditions affecting nerve cells, leading to deterioration of cognitive or motor function, as seen in Alzheimer’s, Parkinson’s and Huntington’s disease.

•A stroke: the sudden interruption of blood supply to the brain, causing rapid loss of brain function, leading to paralysis, speech and vision problems, or death.

The use of biomaterials

The use of human embryonic stem cells for therapeutics to aid brain disorders has come with success but raises ethical questions. It can be argued that the development of biomaterials is a better approach.

•For the treatment of spinal injuries, neural grafts and biomaterial scaffolds are employed for functional recovery, physical support and help foster axonal regeneration. Strategies like electrical stimulation and growth factor delivery further aid neuronal regrowth.

•Neurodegenerative diseases prompt the development of 3D brain tissue models, organoids and neural implants to understand disease mechanisms whilst stem cell therapies, including induced pluripotent stem cells (iPSCs), restore neural function.

•Stroke therapies utilise biomaterial scaffolds and injectable hydrogels to promote neuroprotection and enhance functional recovery.

Hydrogels: application in stroke recovery

Hydrogels provide therapeutic benefits through drug delivery, tissue regeneration and wound healing, including direct injection into stroke cavities and forming protective barriers in the brain post-stroke.

Derived from natural or synthetic polymers, they form a 3D structure, absorbing biological fluids within the body. They are flexible and resemble tissues which can be tailored for specific applications. They also play a crucial role in aiding neurological regeneration for stroke patients through multiple mechanisms.

Firstly, they provide a scaffold for cells to adhere to and grow within, facilitating cell migration and tissue regeneration. Secondly, hydrogels can deliver therapeutic agents (growth factors and stem cells), promoting neuronal survival, angiogenesis and modulation of the inflammatory response, essential for recovery. Thirdly, their biocompatibility ensures sustained release of therapeutics without adverse immune reactions. Lastly, their physical properties can mimic the brain’s native tissue environment, fostering appropriate cellular behaviour and functional recovery. In essence, hydrogels offer a versatile platform for neurological regeneration.

Things to consider

Concerns linger over longevity, immune rejection, and unforeseen risks of biomedical interventions. Legally, adherence to regulatory frameworks, patent protection and insurance coverage are paramount for ensuring safety and accessibility. Ethically, emphasis lies on informed consent, equitable access, especially in developing nations and addressing social injustices. Who deserves this treatment and why?

My final thoughts

Whilst all sides present a fair argument, I am inclined to take the equitable approach in providing access to these treatments. The choice should be with the patient, neither the law or the socioeconomic circumstances of the individual should intrude on their autonomy or dictate their access to treatment. However in reality this is not always the case.

The long term effects of using biomaterials, particularly hydrogels are a controversial topic. Nevertheless, their use for stroke treatment has shown promising potential, with wider applications to other neurological cases. Caution should be taken with experimental treatments as their long term effects remains to be seen.

Hearing – a natural ability we possess and one of the five senses crucial to human experience. Yet, it is often overlooked. Hearing loss is an invisible disability affecting 1-in-6 adults in the UK. This sparked my curiosity about how hearing loss, whether congenital or acquired, impacts quality of life. Especially in terms of its social aspects. This article published in May 2022 states that factors such as “differences in cognitive abilities and age-related changes may exacerbate the problem”.

What Are Cochlear Implants?

A cochlear implant is a small yet complex electronic device designed to provide a sense of sound to individuals who are profoundly deaf or severely hard of hearing. It consists of an external component placed behind the ear and a second component surgically implanted under the skin.

How Do They Work?

As shown by the diagram above, cochlear implants consist of a microphone which captures sound from the surroundings. Detected sounds are sorted and organised by a speech processor. A transmitter and receiver/stimulator then receives signals from the speech processor and transforms them into electrical impulses. These impulses are gathered by an electrode array and transmitted to various sections of the auditory nerve and finally to the brain which recognises the electrical impulses as sound.

Quality of Life

During my research, I found that one aspect to consider within the deaf community is listening effort – referring to the cognitive exertion required to understand and process auditory information. If it is more challenging to hear, it must also be exhausting to communicate. While it may require some acclimating, with the use of cochlear implants, the ability to engage in social settings becomes possible. This can significantly improve quality of life for deaf individuals by reducing the need to be in a constant state of high listening effort.

Individuals with hearing loss often face challenges with employment leading to socioeconomic disparities. Statistics show that the employment rate for those with hearing loss stands at 65%, in contrast to 79% for those without any long-term health issues or disabilities. These figures reflect the situation in the UK – a well-developed country. However, differences in employment rates may be greater in less-developed countries with limited access to healthcare facilities and lack of awareness about hearing loss. A study from Cambridge University found that individuals with cochlear implants reported higher levels of employment and income.

The Downside

Perspectives on deafness vary among individuals. I found this article particularly captivating as it delves into how some may embrace deafness as a cultural identity. The deaf community have developed their own mode of communication over centuries through sign language. To them it is not simply a means of communication but also a part of belonging to a community.

The widespread use of cochlear implants raises concerns within this community about the potential loss of their language and culture. In fact some deaf parents go as far as to request pre-implantation genetic diagnosis (PGD) to ensure their children will be born deaf, and thus take part in their culture and lifestyle.

Conclusion

Cochlear implants overall represent a remarkable advancement in technology for individuals with hearing loss. While they may not be a cure-all, they have the potential to enhance quality of life by restoring access to sound and facilitating better communication. However, it is crucial to recognise that the decision to pursue cochlear implants is deeply personal and not every deaf individual may choose to use one.

Engineering Bronchial Tissue through the use of Scaffolds to Treat Asthma

So what is Asthma?

Asthma is a common lung condition that causes occasional breathing difficulties. Symptoms include wheezing, a tight-feeling chest, breathlessness and coughing. During an asthma attack, airways become inflamed and the walls of the bronchi constrict, as you can see in the image below. This reduces airflow into the alveoli.

Triggers include infections, allergies, pollution and exercise, but attacks can also occur randomly, which is what I personally tend to find. Asthma affects more than 300 million people world-wide, so finding a cure is essential.

So what is Tissue Engineering?

Tissue engineering refers to the assembly of functional constructs that restore, maintain, or improve damaged tissues or whole organs. In this process, cells are selected, cultured and proliferated. For cells to proliferate, a scaffold is required. A large variety of cells are used for regenerative tissue engineering. These include:

• Allogenic cells = cells harvested from other individuals of the same species, including embryonic and mesenchymal stem cells.
• Autologous cells = cells harvested from the patient and reintroduced in a secondary site.

Tissue engineering in Asthma

Majority of bronchial tissue engineering studies have involved autologous and allogenic cells, including the use of human bronchial epithelial cells (HBECs) and human bronchial fibroblastic cells (HBFCs). The earliest study of this took place in 1999, where Zhang et al., seeded HBECs into a collagen-scaffold gel after HBFCs were incorporated, resulting in a tissue-engineered bronchial mucosa. This scientific success has lead to the continued study of bronchial disorders such as asthma.

Collagen – the best scaffold?

The role of scaffolds in bronchial tissue engineering is to provide an environment that resembles a native extracellular matrix, promoting proliferation and differentiation. When selecting the material for a bronchial scaffold, biocompatibility and strength must be considered.

Collagen is one of the most abundant structural proteins within tissues, offering high-strength, biocompatibility and even promoting cell proliferation. Even its fibre-structure is ideal -trapping growth factors and allowing HBECs to migrate and attach on the surface, hence allowing visualization under a microscope and study of bronchial disorders. Perfect, right?

Not quite… Collagen as a scaffold has limitations. Often extracted from animal tissues such as pigs or cows, collagen has poor immunogenic properties, posing a risk of carrying diseases.Therefore, collagen must be combined with immunosuppressants which increases cost. This use of animals also creates ethical and religious debate which I worry may limit the demographic that this innovation could target.

The Future

Despite these limitations, the use of bronchial tissue engineering should not be underestimated. I believe tissue-engineered bronchial mucosa acts as an effective three-dimensional model for the further study of this disorder and paves the way for the development of future effective therapeutic interventions, offering hope to millions of people world-wide, including myself.

If, like me, you feel inspired by this, check out Dr Kotton’s current and ongoing research into “rebuilding lungs“. I’m excited to see how this progresses, perhaps making use of tissue-engineered bronchial mucosa as a combined model. The future of asthma treatment looks bright.

Links/Sources:

• https://www.sciencedirect.com/science/article/pii/S0091674901404192
• https://utswmed.org/medblog/pediatric-asthma-tips-parents/
• https://www.nhs.uk/conditions/asthma/
• https://www.hse.gov.uk/asthma/lungs.htm#:~:text=Cross%2Dsection%20of%20normal%20bronchiole,actually%20block%20the%20smaller%20airways.
• https://cks.nice.org.uk/topics/asthma/background-information/prevalence/
• https://www.nibib.nih.gov/science-education/science-topics/tissue-engineering-and-regenerative-medicine#:~:text=The%20goal%20of%20tissue%20engineering,limited%20use%20in%20human%20patients.
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475566/
• https://www.sciencedirect.com/science/article/pii/B9780081025611000166
• https://www.biolinscientific.com/blog/what-is-biocompatibility
• https://www.medicalnewstoday.com/articles/vegan-collagen
• https://mokosh.com.au/blogs/blog/the-ethics-of-collagen-supplements#:~:text=A%20significant%20concern%20around%20using,a%20potentially%20less%20controversial%20source.
• https://www.anec.org/en/structure-of-collagen.htm
• https://pubmed.ncbi.nlm.nih.gov/16024520/#:~:text=The%20bronchial%20mucosa%20contributes%20to,membrane%20progressively%20unfold%20on%20inflation.
• https://www.bu.edu/articles/2023/stem-cell-therapy-lung-health-and-disease/

Approximately 45% of the mass of the human adult body is muscle tissue.

Serge Ostrovidov, PhD et al.

Muscles are critical in locomotion, prehension, mastication, ocular movement, and other dynamic activities such as body metabolic regulation. Myopathy, traumatic injury, aggressive malignant tumour extraction, and muscular denervation are the most prevalent clinical indications for therapeutical or cosmetic reconstructive muscle surgery. There are three types of muscle tissue: smooth muscles in the stomach and intestines, cardiac muscle in the heart, and skeletal muscle throughout the body. Skeletal muscle, which we will focus on in this blog, majorly consists of myocytes, the multinucleated contractile muscle fibres.

Methodology of SMTE

While Skeletal muscle tissue engineering (SMTE) has been introduced to the world of biomedical engineering for more than two decades, it remains a significant challenge, with numerous techniques being developed constantly to accomplish this.

The muscle cells are first isolated from the patient or a donor, followed by culturing, where the cells effectively differentiate and develop in the nutrition-rich medium. The muscle tissue is then generated in three methods, which form different specialized muscle cells: myotube formation under controlled topography, cell sheet formation with a hydrogel matrix, and muscle bundle formation. The well-developed and functional tissue is then transplanted back to the patient.

Limitations

This is the traditional way of engineering skeletal muscle tissue, but it still faces some limitations. Though cells could be isolated from the patient, the tissues generated from a donor could trigger immune responses in the recipient’s body, causing rejection and the necessity for immunosuppressive drugs. These medications come with their own risk, like increased susceptibility to infections and organ damage. Moreover, traditional tissue engineering often focuses on preparing damaged muscle tissue rather than promoting regeneration. Thus, the regenerative potential of the SMTE tissue may be insufficient to restore full muscle function, especially in cases of extensive injury or degeneration quantitatively and qualitatively due to ageing. On the other hand, ensuring the long-term functionality of transplanted muscle tissue is also a significant challenge. Without adequate vascularization and support structures, it may encounter degradation or necrosis over time, leading to repeated interventions.

3D Print Muscle Tissue

I came across a piece of news published in 2023 written by Michael M., mentioning the researchers at the Terasaki Institute for Biomedical Innovation have developed a fascinating new technology of 3D printing skeletal muscle tissues with bioink invented by the researchers, which could mimic the natural muscle formation.

The science of muscle 3D printing

The three parts of the bioink are polylactic acid (PLGA) microparticles, myoblast cells, and a hydrogel based on gelatin. The PLGA microparticles sustainably release growth factor-1 (IGF-1), an insulin-like hormone that’s necessary for healthy bone and tissue growth. The production process of muscle tissue is more complex than it looks. Myoblast cells were deemed viable three days after printing and successfully developed into complete synthetic muscle tissue over the next ten days, eventually contracting on their own, just like normal muscle tissues! In order to determine if the cultured tissue was viable in living organisms, the tissue was implanted into mice. The researchers were then able to confirm that the cultured tissue was successfully accepted by the body and combined with the existing muscle tissues.

Summary

The ability to 3D print muscle tissue represents a significant advance in medicine. Using this technology, muscle mass replacement could be revolutionized by mimicking the natural process of muscle development. Prior to the possibility of treating humans, further clinical studies and testing will be necessary to confirm the safety of this process before the possibility of treating humans. What’s for sure, however, is that 3D printing muscle tissue has a highly promising future in medicine. I, as a biomedical science student, am also looking forward to the further development of skeletal muscle engineering.

References:

1. Ostrovidov, S., PhD et al. (2014). Skeletal Muscle Tissue Engineering: Methods to Form Skeletal Myotubes and Their Applications. Tissue Engineering Part B Review, 20(5), pp. 403-436. doi: 10.1089/ten.teb.2013.0534

Our lecture surrounding ethical dilemmas within the scientific community has really stuck in my brain. Ultimately everyone views situations differently due to individual moral compasses. It also highlighted a key argument: what do you do with good data from bad studies? During the lecture, I concluded that ignoring the data doesn’t undo the crimes committed however it could lead to advances in the medical and scientific field. To see if others shared my views I googled, “unethical studies that generated good data”.

My research revealed it was only in 1945 during the Nuremberg trials that there was an ethical awakening due to prisoner exploitation within concentration camps for medical research. This established the Nuremburg code, which set out to prevent such atrocities from happening again. Unfortunately, studies were conducted before these laws or by people who have no regard for ethical laws now.

Henrietta Lacks

The Henrietta Lacks study is a poignant example of this moral dilemma. Lacks, was in hospital with cervical cancer, unknowingly cancer cell samples were taken and given to researchers. Experiments led to the finding of HeLa cells which became a catalyst for medical advancements in cancer treatments and immunisation.

How do HeLa cells work?

By understanding their function and immortality it is clear they’ve saved countless lives, but the unethical methods by which data was obtained has resulted in controversy.

The lack of consent and financial restitution towards the family outline the ethical complexities of using this data. Surprisingly, Lacks family have started a movement  #HeLa100, promoting the use of HeLa cells, and wish for her legacy to continue. Arguably, there is now familial consent so can the data be classed as ethically sound?

He Jiankui

The He Jiankui gene editing study also interested me, as unlike Henrietta’s story this is more recent, 2018. Jiankui lead unauthorised experimentation on embryos to try and counter HIV, by modifying embryonic genomes to become resistant against HIV – using techniques shown in the diagram. This produced potential benefits within gene editing technology. However rigorous investigations after the research was published led to this statement  “He had defied government bans and conducted the research in pursuit of personal fame and gain” resulting in a sentence of 3 years imprisonment. Fortunately the embryos in question have become three healthy children.

This creates the dilemma – can we use these techniques?

My thoughts

Upon reflection, I think both studies generated data that has led to great scientific discoveries, which fortunately haven’t had negative consequences. It is estimated that HeLa cells have gone on to save over 10 million people worldwide. I think that statement alone argues that we should be using this data even if it was obtained by unethical means. These cells have also contributed towards development of vaccines, preventing the spread of disease and minimizing impact – e.g. the COVID-19 vaccinations.

I also believe that although He Jiankui conducted an unethical study, it’s positive outcome brought about an unbelievable breakthrough in gene editing science. It could create treatments for inherited disorders, that are currently incurable.

Overall, I think the data generated from these studies has led to life changing scientific breakthroughs that if ignored could result in unnecessary deaths and stress on hospitals. But this is just my view, so I would like to put this out there what would you do with good data from bad studies – would you use it?