Regenerative medicine is the study of methods to regenerate human cells and tissues, while tissue engineering aims to create 3D models to restore or maintain tissues and organs. The drive for advancements in this research is fuelled by the organ shortage crisis. Medical school interviewers will often ask applicants about the research they have been reading, medical ethics and NHS hot topics. 

What is Regenerative Medicine?

Regenerative medicine is a term first coined in 1999 and is a discipline concerned with developing methods to treat patients with damaged cells or tissues, usually by either replacing the damaged tissue or repairing it. Multiple methods have been developed including stem cell transplantation, using cytokines or the use of biomaterials. 

Current clinical guidelines aim to treat degenerative disease, such as Parkinson’s or osteoarthritis, with symptom management from a palliative point of view, whereas regenerative medicine aims to cure these illnesses.

For example, Parkinson’s disease arises from loss of dopaminergic neurones in the substantia nigra. Current NHS treatment for Parkinson’s involves

  • Physiotherapy
  • Dopamine agonists
  • Surgery

All of them aim to manage symptoms of the disease. However, the aim of regenerative medicine is to cure Parkinson’s by using stem cell therapy to replace destroyed neurons. 

Tissue Engineering Fundamentals

Cardiac tissue cannot spontaneously regenerate like the majority of tissue within the human body, hence patients who survive major heart attacks will likely suffer with a degree of heart failure for the rest of their lives.

The goal of tissue engineering is to use bioengineering to grow live tissue in a laboratory to transplant to humans, thus restoring dead or damaged tissue within their body. 

There are multiple methods of tissue engineering currently being developed. In a healthy human, the body is full of extracellular matrices made from proteins that provide support to cells and are vital to successful cell growth and movement. Scaffolds are artificial, biocompatible matrices that imitate extracellular matrices and play the same role in cell growth.

They are typically made from:

  • Polymers
  • Biodegradable metals
  • Bio-ceramics
  • Carbon-based nanomaterials.

Scaffolds can either be directly implanted to the patient, or combined with donor cells which develop to make artificial tissue suitable for transplant.

It is important for tissue engineering materials to be biocompatible- meaning a material that can function inside the body without a negative systemic response. You can think of this as a similar principle to organ rejection post-transplant. Implantation of materials that are not biocompatible can result in catastrophic outcomes for the patient.

While tissue engineering currently plays a small role in standard NHS practice, we are starting to develop treatments that will revolutionise healthcare once approved. Great Ormand Street Hospital in London has played a large role in developing whole organs (‘organoids’) in a lab, which we may be able to transplant to infants with congenital defects.

They have also managed to successfully transplant a bioengineered trachea into a young child with long-segment tracheal stenosis.

Role of Stem Cells

Stem cells are incredibly unique in their properties and as a result have saved the lives of many patients worldwide. Stem cells are able to go on to produce a vast amount of different types of cells, unlike other cells in the body.

There are two main categories of stem cells:

  • Embryonic
  • Adult stem cells

Adult stem cells are made in the bone marrow and released to either form specialised cells (e.g. B cells, neurons, etc) or multiply to form more stem cells. Embryonic stem cells are found in the inside of human blastocysts- clusters of cells produced by an egg five to six days after fertilisation. 

Embryonic stem cells are ‘pluripotent’ while adult stem cells are mostly ‘multipotent’. Pluripotent stem cells can develop into any cell found in the human body, whereas multipotent stem cells, while still able to differentiate into multiple different types of cell, are only able to form a number of specific cell types.

Both pluripotent and multipotent stem cells are useful in tissue engineering. 

That being said, there is a type of adult stem cell known as ‘induced pluripotent stem cells’ which are multipotent adult stem cells which have been modified in a lab to behave like pluripotent embryonic stem cells. These cells are not as well known by laymen as they were only first mentioned in the literature in 2006. 

While stem cell research is currently one of the largest areas of development, we are only routinely offering stem cell therapy for bone marrow transplants for patients diagnosed with blood disorders, such as lymphoma and leukaemia. This is done via transplantation of a healthy donor’s haemopoietic stem cells from their bone marrow into the patient. 


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Advances in Growing Organs for Transplantation

Organoids are lab-grown, three-dimensional tissues derived from either pluripotent or multipotent stem cells. This process is called ‘organogenesis’ and is aided by bioengineering techniques. The long-term goals of organoid research are to use organoids to explore disease mechanisms but also to potentially transplant the organoids into patients. Currently, 

There have been multiple exciting breakthroughs in organoid research. For example, David Breault of Harvard Stem Cell Institute has devised a method to create beta cells out of intestinal cells. These beta cells are able to produce insulin, meaning this advancement could change the lives of diabetic patients. 

Organoids also show promise in replacing animal models for testing and development of new drugs. This is particularly exciting as many members of the public are uncomfortable with ‘animal testing’, which so far has been the only option for ensuring drugs are safe to give to humans. It is also very useful for studying treatments of rare diseases, where animal testing generally won’t suffice.

While these developments are exciting, they beg the question: have we successfully transplanted any organoids into living patients successfully? The simple answer is: yes. Lab-grown tissues, for organs such as bladder and trachea, have been successfully transplanted into patients.

The advancements are showing great promise for the future, however, there are multiple hurdles for scientists to overcome before this becomes standard practice, especially the concern of toxicity after implantation of foreign materials. 

Bioengineering Techniques: 3D Printing

Bioengineering is an area of engineering concerned with designing materials for biological systems. There are multiple subspecialist areas of bioengineering, including regenerative medicine and tissue engineering, biomechatronics, and biotechnology. 

3D bioprinting is an area of bioengineering that aims to use bioink to create artificial organs or tissues in an effort to solve the organ donor crisis.

Some 3D printed tissues have been transplanted already, namely a 3D printed ear that had been developed from the patient’s own cells. That being said, we are still relatively far from being able to transplant 3D printed major organs.

3D bioprinting is extremely complex and involves many challenges. While we may be able to produce an organ that looks like a heart, we still have the challenge of achieving a vascular supply to the organs, ensuring the organ is functional, and ensuring drugs will interact with the organ in the same way they would with a normal heart.

Ethical and Regulatory Considerations

While stem cell research has the potential to save many lives, there are some important ethical issues that require consideration.

  • Firstly, extracting embryonic stem cells kills the blastocyst which they are derived from which many people view as a form of abortion. Abortion is a procedure that most mainstream religious groups fundamentally disagree with, meaning that embryonic stem cell research is considered extremely unethical to these groups.

Some cultures are uncomfortable with this to the extent that President Bush has publicly stated that he does not support embryonic stem cell research as it is equivalent to taking a human life.

  • On the other hand, it is argued that the use of embryonic stem cells is no different ethically than discarding unused embryos at IVF clinics, which is a procedure that many people agree should be available to couples facing fertility issues. 

As stem cell research involves the use of human embryos, all research is regulated by the Human Fertilisation and Embryology Act of 1990. This is the same body that regulates invitro fertilisation (IVF) procedures. The act regulates what institutions/organisations are allowed to use embryos or donated sperm/egg cells to ensure all procedures are of an ethical nature. 

  • Statistics published by the 2004 Public Attitudes to Science Survey showed that 66% of the UK public do not feel that they are well informed about stem cell research, and only 57% believe that the benefits of the research outweigh the risks. This survey prompted campaigns aimed at members of the public in an effort to improve public education on the topic. 

Future Directions and Potential Impacts

While we have made excellent developments in regenerative medicine, there is plenty of scope for further advancements in the future. One particular area of development is for patients with nerve injury. Hydrogels are electrically conductive biomaterials that can aid the remyelination of nerve cells. This may be particularly useful in patients diagnosed with demyelinating diseases, such as multiple sclerosis. 

There is a big push to further develop organoids so they can better emulate normal organs in their anatomy, functionality, and physiology. It will not be possible to transplant an organoid heart, for example, without these properties being met. 

Further progression in this field will not be successful without multidisciplinary input. Regenerative medicine research requires input from bioengineers, mathematicians, clinicians, and patients in order to develop high-quality treatments. 


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