Hopping rabbits herald breakthrough in tissue engineering

A team of NIH-funded scientists and veterinarians at Columbia University, the University of Missouri, Clemson University, and the Medical University of South Carolina, have this week announced a significant advance in tissue engineering, for the first time they have used cutting–edge tissue engineering technology to produced a moving joint, in this case the hip, in rabbits.  A press release on the NIH website discusses the work in some detail, and those with a subscription can read the original research article in the Lancet.  This is not the first paper to describe the production of bone or cartilage using tissue engineering, but it is the first time that the two tissues have been regenerated together to produce a moveable joint, and represents a significant step forward in terms of the complexity of tissue that can now be engineered.

Rabbits are a popular experimental model for the study of bone repair and regeneration; the structure of their bones is very similar to that seen in larger animals including humans, for example unlike some smaller rodents they have structures known as  Haversian canals that affect bone growth and repair, while their size allows more complex surgery than is possible with smaller rodents.

Tissue engineering techniques we have discussed previously, such as the artificial lung, involved seeding a scaffold, were created by stripping cells from donor tissue, seeding with stem cells, and then allowing the cells to grow in vitro to produce a functioning organ. The technique reported this week differs in that the scaffold was made from an artificial bio-polymer, and rather than implant stem cells into the scaffold and growing the tissue in vitro, they coated the scaffolds with the growth factor known as TGFβ3 and then implanted it into the rabbits. TGFβ3 attracts bone and cartilage precursor cells to the scaffold, where they multiply and after a few weeks have formed a functioning joint.  When they compared scaffolds coated with TGFβ3 to bare scaffolds, they observed that more precursor cells were recruited to the scaffold when TGFβ3 was present, and that the rabbits transplanted with TGFβ3-coated scaffolds moved more easily when assessed one to two months after surgery, indeed the joints were able to support the weight of the rabbits without any limping.

Rabbits play an important role in medical research. Image courtesy of Understanding Animal Research.

This technique is significantly simpler than those approaches that require stem cell seeding and in vitro growth prior to transplant, and might be especially useful for younger hip transplant patients, individuals aged 65 or younger. Younger patients would be expected to recover more quickly, have fewer co-morbidities that would be aggravated by staying in bed for a prolonged time to allow the tissue to regenerate, and would benefit more from not having to have hip operations every 10-15 years as is currently the case with metal hip joints.  For more elderly patients metal hip joints are likely to remain the best option.

So does this technique replace that used in the tissue engineering studies we have previously discussed? Well, the answer is no, for some applications either approach might work, but for others, for example the artery and lung transplants, the tissue needs to be capable of functioning immediately following transplant. One aspect that is being evaluated elsewhere is the use of biopolymer scaffolds, which are being used with stem cells to produce replacement blood vessels, and may provide a more flexible and reliable alternative to the use of decellularized tissue.

It’s an interesting development, and one that again highlights how quickly things are happening in the field of tissue engineering. Of course it will be some time before clinical trials in humans start, before then this technique must be evaluated in a larger animal, probably a pig, to determine whether tissue regeneration on the scaffold is rapid and effective enough in a model of comparable sizes to humans. Only if these tests are successful will this technique warrant evaluation in a human clinical trial.

Paul Browne

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