The University of Southampton

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Engineering Bronchial Tissue through the use of Scaffolds to Treat Asthma

Following the lecture on tissue engineering, I felt inspired by the emerging technologies and how these might lead to new therapies. I began to reflect on my own health condition of asthma, and became curious if this relatively-new innovation could be the answer to my future health. Having lived with this condition for almost 21 years, I have always wondered could we, one day, cure asthma entirely?

I began to research the future of tissue engineering in relation to lung conditions, and was particularly interested in Hafeji et al.,’s (2019) paper, Scaffolds for Tissue Engineering of the Bronchi, which has inspired this blog.

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.

Want to know more about how Asthma works? Check out this video!

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.

The fibre-structure of collagen

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:

Grow yourself a backbone!

Familiar with that phrase? Well, Scientists have given this saying a whole new meaning… A future where damaged spinal cords can be regenerated through the medical application of stem cells isn’t as far away as it once seemed…

So what is a stem cell?

Stem cells are cells produced by the bone marrow that can differentiate into a specialised cell type, and are even capable of self renewal. They can be isolated from adult tissues or grown within a laboratory. The stem cells that are isolated from adult tissues are referred to as multipotent, meaning they can only change into a particular type of cell. We also get pluripotent stem cells, which are often derived from embryonic cells. However, these can cause quite the debate, with views on ethics differing. Therefore, the use of Induced Pluripotent Stem Cells (IPSCs) is often preferred. Like embryonic stem cells, IPSCs are also pluripotent, meaning they can divide indefinitely and differentiate into almost any cell type, but they don’t raise the same ethical concerns due to originating from adult tissue.

Restoring mobility and function to those with spinal cord injuries

Therapies involving stem cells hold great promise for treating a variety of medical conditions, particularly spinal cord injuries. Stem cells taken from a patient’s skin or blood cells are used to create IPSCs. These are then coaxed into becoming progenitor cells, which are specialised to differentiate into spinal cord cells. Once these progenitor cells are transplanted back into the patient, they can regenerate part of the injured spinal cord, offering hope for recovery. Sounds great, right?

What could possibly go wrong?

Undifferentiated IPSCs pose a risk to patients, with a chance of forming tumours. This limits the therapy’s safety and efficacy, questioning the future of stem cell treatment. Luckily, researchers have developed what’s known as a microfluidic cell sorter, which you can imagine to be like a sieve. This device removes undifferentiated cells without harming fully-formed progenitor cells. It can sort over 3 million cells per minute and can be scaled up by chaining multiple devices together, sorting more than 500 million cells per minute! Plus, the plastic chip that houses the sorter can be mass-produced at low cost, making widespread implementation feasible. Cheap and cheerful!

So how does it work?

The microfluidic cell sorter operates based on the size difference between residual, undifferentiated pluripotent stem cells and progenitor cells. Pluripotent stem cells tend to be larger because they have numerous active genes within their nuclei. As cells pass through microfluidic channels at high speeds, centrifugal forces separate them based on their size. By running the sorter multiple times at different speeds, researchers are able to remove these larger cells that are associated with a higher tumour risk. Problem solved!

The future…

Although the sorter doesn’t eliminate 100% of undifferentiated cells, it significantly reduces the risk, massively enhancing the safety of stem cell treatments. Further studies including large-scale experiments and animal models are underway to validate these findings. If successful, this sorter could improve efficacy and safety, paving the way for broader applications of this revolutionary technique. The development of this microfluidic cell sorter shows a significant advancement in the field of stem cell therapy. It brings us closer to realising the full potential of stem cells and the use of other regenerative medicines for conditions like spinal cord injuries. With research ongoing and technological innovations forever evolving, the future of improved healthcare looks promising.

Looks like you will be able to grow a backbone after all…

Links:

https://stemcellthailand.org/induced-pluripotent-stem-cells-ips-ipscs-hipscs/

https://www.nhs.uk/conditions/stem-cell-transplant/#:~:text=Stem%20cells%20are%20special%20cells,cells%20%E2%80%93%20which%20help%20fight%20infection

https://www.youtube.com/watch?v=i7EN6l9wqDU

https://cells4life.com/2024/02/the-tiny-device-set-to-improve-stem-cell-therapy/

https://novavidath.com/services/stem-cell/?lang=en

https://doi.org/10.1002/path.1187