Muscle tissue successfully xenotransplanted in new study

The possibility of using animal parts to overcome human organ shortages moves one step closer following the successful transplant of rabbit skeletal muscle tissue into rats, by a team led by the UCL Institute of Child Health.

Not only did the xenotransplanted muscle tissue retain its biomechanical properties, but it also triggered an anti-inflammatory and immunosuppressive response, preventing the typical immune system ‘attack’ that can lead to organ rejection.

The critical shortage of human organs available for transplantation has stimulated researchers to explore synthetic and animal-derived body parts, but the latter brings with it the risk of organ rejection and the necessity for lifelong medications in order to prevent such rejection. A further problem is replacing functional tissue, which remains a major challenge in medicine.

In the study, published in the journal PNAS (Proceedings of the National Academy of Sciences of USA) and funded principally by the Medical Research Council (MRC) and Sparks Charity, skeletal muscle tissue was removed from rabbits, washed with detergents to strip it of cells - in a process known as decellularization – and then transplanted into rats with and without muscle stem cells.

The team examined the immune response of the rats to the rabbit tissue. They found a significantly lowered immune response, with less T-cell activity (a type of immune cell instrumental in rejection) and evidence of delayed biodegradation; a process by which the immune system normally erodes transplanted organs. Two weeks following the operation, new blood vessels had grown between the host and transplanted tissues, with the donated muscle stem cells still intact after a month.

Animal-derived tissue is already used in some surgical procedures. Bovine (from cows) or porcine (from pigs) heart valves are sometimes used to repair children’s hearts at Great Ormond Street Hospital. Similarly, the small intestine from a pig, stripped of cells, can be used to rebuild abdominal wall defects in children. However, animal-derived materials do not have a long lifespan in the human body – researchers believe that the human body slowly rejects them, which may explain why these heart valves only last about ten years. The advantage of the new approach developed in the study is that it may prevent implanted tissues from being rejected in the future.

Dr Jonathan Fishman, MRC-Sparks Clinical Research Training Fellow, UCL Institute of Child Health and first author of the study, says: “Our study used a regenerative medicine approach to explore ways of overcoming both the current lack of available organs for transplantation and organ rejection. Given the long waiting lists for organs, we need to explore the option of using animal organs and tissues to meet the gap between supply and demand. While some patients might not like the idea of having an animal part inside them, animal tissue is already used to repair some heart defects.”

Dr Paolo De Coppi, Consultant Paediatric Surgeon at Great Ormond Street Hospital who coordinated the study, says: “The anti-rejection drugs currently taken by transplant patients are toxic to the kidneys and can increase the risk of children developing infections or cancer, so we need to find ways to develop organs that don’t trigger rejection. The goal for surgeons is to one day have off-the-shelf organs ready to transplant within a matter of days. However, although we have successfully transplanted a tissue-engineered trachea, it remains very difficult to find matched human donors for neonates or infants who are born with a severe malformation. Animal-derived tissue may offer a solution, but we are not there yet. The next stage of our research is to assess whether the effects observed in our study can be reproduced in larger animals and ultimately humans.”

Professor Gudrun Moore, Chief Scientific Advisor at Sparks says: “Funding research that helps prevent, diagnose, treat and cure conditions affecting the health of children is at the heart of what Sparks does.  We are very excited by this cutting edge research which brings us one step closer to regenerating fully functional muscles without the fear of rejection.  This has great potential for children who need a transplant, but for whom the options are currently limited.”