The University of Southampton

Tag: tissue engineering

From stealing organs to growing organs from pigs: the lengths humans will go to survive.

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As a registered organ donor before the opt-out system, I could not fathom why people would not want to donate their organs. It baffled me, and yet in 2019, I was in a debating competition where I had to oppose the idea of organ donation as an opt-out system – my point was simple. Surely the argument that this is a violation of a donor’s autonomy and implies given consent, would always triumph over the utilitarian view, that it should be the greatest good for the greatest number, right?

The original donor card required for the opt-in system.

In 2020, the UK introduced a new law, the ‘opt-out’ system. Many believed this diminished a donor’s autonomy, yet, by definition, there is still a choice in opting out. The new law made sense to me, when around 6,945 people are currently awaiting a transplant in England, I found it hard to understand the counter-argument.

Dr. Jon Dawson covered the ideas of organ donation and autonomy throughout his lectures. I saw a wide range of views in one group of students of a similar age and with the same privilege of higher education. Dr. Dawson put forward the Alder Hey case, where about 850 organs were being harvested after death without any form of consent from either the patients or guardians.

A video briefly describing the Alder Hey Scandal.

There was a large consensus that this was not okay from the class, the lack of adequate consent when removing organs and tissue from patients was barbaric, nonetheless arguments can be made that people uneducated in the opt-out system are therefore giving ill-formed consent.

This case made me think of the book Never Let Me Go by Kazuo Ishiguro, where clones are created for the purpose of organ donation, and once they have donated around three of their organs, their short lives are over. Although this dystopian novel seems far stretched, the premise behind it still stands. Especially as since 2015, advancements in tissue engineering has shown animals as a viable surrogate for growing organs.

In 2019, Hiromitsu Nakauchi had the first approved experiments to allow a human-animal hybrid to grow fully. This sounds like some werewolf science-fiction, Morbius esc (awful movie); however, this could be the key to the current organ shortage. In an ideal world, we could grow the organ required at the drop of a hat- but here is a scientific solution where we could grow organs within animals and harvest them without invasive surgery on humans, or an ethical debate of autonomy.

Now, PETA and animal rebellion may be opposed to this idea, but I think animals will forever hold a place in scientific research, so could this be a legal viable solution? What do you think?

Well, in January 2022, the first pig to human transplant was done; a genetically engineered pig’s heart was harvested and placed into a patient. Although this required a lot of medication and extra resources, the heart did work prolonging the patients life for two months. This was a major breakthrough- can we now combat our organ shortage through animals?

Whether genetically modified pigs or human-animal hybrids hold the future in organ donation, ethics must be considered- we can not return to being so desperate as to take organs without consent. The podcast below is an informal discussion on organ donations with the opinions of two biochemists discussing frankly the possible future of organs, ethics and consent for further insight into this medical and ethical minefield.

https://open.spotify.com/episode/4inRLDaXEcnROyTexaC3WQ?si=7988ff562cb04df4
STEM Sundays a podcast by Lara Etheridge and Yasmin Yardley discussing organ donations, ethics and movies.

Commercial Autogenic Cell Therapy Evolution at a Glance.

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The lectures I recently received about tissue engineering piqued my interest, specifically with the commercial availability of autogenic cells such as CarticelTM and as I looked further the development of such products was very interesting.

The 4 generations of autogenic chondrocyte implantation (ACI):

First Generation:

A 1st generation ACI procedure is shown in the video below where you can see the harvesting of periosteal tissue from the tibia, suturing of the periosteum into the knee joint, securing with fibrin glue and finally the injection of chondrocytes below this periosteal patch. Genzyme is a company which delivers this service and has reported success rates of 70-90%. Problems with this procedure include overgrowth of the implanted cells which can degrade joint function and cause pain; however this can be easily fixed by the shaving away of excess cartilage. Procedures of this type cost around $40,000, far too expensive for many people, especially in countries without nationalised healthcare such as America where insurance may not cover the procedure.

Second Generation:

Carticel is an example of 2nd generation ACI. A biopsy of cartilage is taken from lesser weight bearing areas so that chondrocyte cells can be isolated and expanded over a period of 4-6 weeks. The expanded cells are reinserted into the damaged joint to form new, healthy cartilage. On their website, Carticel states that their product is intended for the repair of “symptomatic cartilage defects of the femoral condyle caused by acute or repetitive trauma, in patients who have had an inadequate response to a prior arthroscopic or other surgical procedure”. According to the Bioinformant, Carticel autologous chondrocyte implantation costs between $15,000 and $35,000. This cost raises ethical questions because a large subset of people who would benefit from this procedure cannot afford it.

Third Generation:

Spherox is a company which offers 3rd generation ACI with a £10,000 price tag, however the Royal Orthopaedic Hospital (ROH) in Birmingham has provided this procedure and it is now eligible for patients on the NHS according to the ROH website. Spherox works in a different way to Carticel, by taking chondrocytes and producing spheroids of neocartilage composed of expanded autologous chondrocytes and their associated matrix. A sample of healthy tissue is taken from the patient in keyhole surgery and the sample is grown into chondrocyte spheroids. When the spheroids are implanted into the patient’s knee cartilage, they bind to the defective tissue and produce new cartilage tissue. For NHS patients in the UK, Spherox has far fewer ethical concerns regarding cost because the price of the operation is less than the cost caused by such injuries if left untreated to both the NHS and the patient’s quality of life.

The Future:

4th generation ACI therapy has not yet entered mainstream medicine, however various trials are underway. Some research is investigating the role of gene therapy in cartilage repair producing “temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage”. According to this paper, the use of elastin as a scaffold is being investigated, as well as the use of a nonviral gene delivery system to allow mesenchymal stem cells to produce osteogenic growth factors.

Restoring My Old Self- Is tissue Engineering Really the Key?

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From beginning this module, I was exposed to various different topics all under the field of engineering replacement body parts ranging from ethics in research to orthopaedics. However I was surprised to find myself knowing nothing about tissue engineering until the lecture we had on it had taken place. Which was what had inspired me to do some research on the topic.

WHAT IS TISSUE ENGINEERING

Falling under the field of regenerative medicine, tissue engineering bares the goal: to assemble functional constructs that restore, maintain, or improve damaged tissues or whole organs.

It could potentially be used in surgeries in which necrosis (premature cell death in tissues) occurs. It has very considerable potential, for which scaffolds from human tissue are thrown away because of necrosis, and in combination with a patients own cells, could make synthesized organs that won’t be rejected by the immune system.

Because tissues are groups of cells grouped together, its obvious there would be certain cells needed so that tissue engineering can be brought about, the types are:

  • Adult/fetal cells
  • Adult/fetal stem cells
  • Pluripotent stem cells

And these cell sources can be divided based on their origin:

  • Allogenic cells- from a human donor
  • Autogenic cells- the donor and recipient are the same
  • Syngenic cells- from an identical twin
  • Xenogenic cells- from an animal
Allogenic cells
– Adult cells- currently have greatest clinical use
– Using fibroblasts which come from banks (of human donors)
– Available commercially Have a high growth potential		Autogenic cells
– Involved biopsy of cartilage (examination of sample cells from a patient to determine presence/extent of disease)
– From which chondrocytes are isolated and cultured, then implanted (with a biomaterial) back into a damaged joint to form a functional cartilage
– But its controversial and has mixed results
Syngenic cells
Aren’t used commercially		Xenogenic cells
– Aren’t used commercially at all
– Hybrid embryos are allowed to be created
Table summarizing the 4 origins of cell sources

TISSUE ENGINEERING IN PRACTICE

 A science paper published on the National Institute of health mentions: “currently, tissue engineering plays a relatively small role in patient treatment. Supplement bladders, small arteries, skin grafts, cartilage, and even a small trachea have been implanted into patients, but the procedures are still experimental and very costly. “

This means, they have been successful in implanting small tissues into patients, however it comes at a price. On the other hand, more larger organ replacements like the heart and lungs, although have been successfully synthesized in the lab, have yet to be successful in replacing the organ in a patient. But steady progress has been made.  

From another point of view:

A different means in which tissue engineering can provide a useful solution in is plastic surgery:

  • another paper published by the National Institute of Health mentions:

“As a group, reconstructive surgeons are facing more challenging composite defects than ever before coupled with internet and media savvy patients with increasing expectation.”

 And goes on to say:

“Among these approaches, the most attractive concept is tissue engineering.”

 Indicating in order to overcome the increasing expectations of patient’s expectations, and the number of potential patients in the future, by using the concept of tissue engineering. They can meet these demands, and “restore both form and function” to the area in which surgery takes place.

CONCLUSION

To conclude, tissue engineering has brought about potential solutions to various issues in both the medical and cosmetic field. Ranging from lack of potential donors in both of these fields (which means they won’t have to standby and wait for donors in transplant surgeries), to overcoming the severely high demand to of potential patients in the future expecting full restorations in reconstructive surgeries. Meaning, tissue engineering could become a key in which modern medicine can be revolutionized.