June 29, 2020

expert reaction to study reporting a bioengineered scaffold that repairs the uterus and supports live births in rabbits

A study, published in Nature Biotechnology, looked at a bioengineered scaffold that repairs the uterus and supports live births in rabbits.

Dr Douglas Gibson, Research Fellow, University of Edinburgh, said:

“The press release is a balanced and accurate summary of the research, and this is good quality research that is backed up by the data.

“The work expands on existing evidence that the uterus can regenerate after small injuries and shows that a tissue engineered scaffold can help replace a large section of rabbit uterus.  The new section is similar to normal tissue, functional and able to support a rabbit pregnancy.

“Although ~6% of women have uterine factor as a cause of their infertility this could be because of a structural or functional disorder of the uterus.  This research is likely to be most applicable to structural problems possibly as a result of surgery or injury.  This approach could not be used to replace a uterus that has been removed (transplant) as it requires some functional uterus to be present.

“Although the rabbit is more similar to humans than rodents in some aspects, the reproductive approach is very different in rabbits compared to humans.  The key difference is humans spontaneously ovulate and menstruate in a monthly cycle and their uterus goes through monthly phases of remodelling, whereas a rabbit does not.  This is likely to make a difference to any attempts to develop a similar approach for human uterus.”

Prof Darren Griffin, Professor of Genetics, University of Kent, said:

“This is a highly significant finding with great potential for future human application.  For women who suffer infertility due to a severely damaged uterus or because of a hysterectomy then adaptations of this approach may well find clinical application.  Currently, the best treatment available for this problem (which affects about 1 in 16 women with fertility problems) is transplantation of a donor uterus.  As with all transplantation treatments however, the dual problems of lack of donors and tissue rejection are genuine barriers.

“This research in rabbits uses a biodegradable scaffold with the rabbit’s own cells added – this formula is already being researched for other organs in people, so it makes sense that this could be used to reconstruct a uterus.

“Rabbits are however well known for their fecundity, and we do not yet know how successful this approach will be for humans.  Time will tell.

Prof Dusko Ilic, Professor of Stem Cell Science, King’s College London, said:

“The work is coming from Anthony Atala, who is known for his past attempts of urogenital system reconstruction; he pioneered the tissue engineering of bladder¹, urethra², and vagina³.  Even though the first clinical studies showed encouraging results, thus far, none of these techniques were clearly superior to current standards of care or lived to their promise.  To replace the traditional surgical reconstructive treatments and make the tissue engineering technology cost-effective and risk-free for patients, further advancements are desperately needed and mandatory.

“Although the preclinical development presented here with a notion that bioengineering uterine tissue could provide a treatment option for women with uterine factor infertility is an attractive and novel technology, it may not be as close to translation as the authors and many of us would like to see.”

1 Atala, A., Bauer, S. B., Soker, S., Yoo, J. J. & Retik, A. B. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367, 1241–1246 (2006).

2 Raya-Rivera, A. et al. Tissue-engineered autologous urethras for patients who need reconstruction: an observational study. Lancet 377, 1175–1182 (2011).

3 Raya-Rivera, A. M. et al. Tissue-engineered autologous vaginal organs in patients: a pilot cohort study. Lancet 384, 329–336 (2014).

Prof Gudrun Moore, Professor of Molecular Genetics, UCL, said:

“I think this is an excellent study using rabbits as a model, with detailed histochemical and biochemical analysis and all the appropriate controls.  I believe this type of experiment offers real hope for the 6% of women with uterine infertility and pushes forward the field in the hope that one day the use of biodegradable polymer scaffolds seeded with autologous cells taken from the uterus of infertile women may help achieve normal pregnancies and births, although we need a lot more research first.

“More preclinical studies are needed to increase the number before clinical studies can be performed in humans.”

Prof John Hunt, Medical Technologies Innovation Facility, Nottingham Trent University, said:

“Only rabbits with cell-seeded constructs had normal pregnancies (four in ten) in the reconstructed segment of the uterus and supported fetal development to term and live birth.  This conclusion in the precise detail is crucial as the reproductive outcomes data (Table 1) indicate that unseeded scaffolds are essentially equivalent to cell seeded scaffolds in terms of these outcomes.

“The fetal development in the replaced part of the uterus beyond the excellent tissue reconstruction is the valuable nugget of evidence that demonstrates the tissue engineering approach is capable of regenerating tissues that are functional and correct to the site they were implanted.  If this is to be translated forward to humans, it would need to be demonstrated that the person receiving this construct can not only bear offspring but also would have a pain free normal life without complications of fibrosis and inflammation.  We know from this work in rabbits that the addition of cells to scaffolds provides function, but equally as important is to know that it can provide improved integration of the implant in to the person, which would result in a significantly better quality of life in the long term – so we need more research first in order to know that.

“It would be very interesting to follow the animals through a full long life with multiple successful pregnancies and determine this regeneration – humans live a lot longer than rabbits.  The next experiment is not a partial replacement of the uterus but a total replacement of the uterus.  This would provide the evidence for the need to provide the cell loaded scaffold, rather than just the scaffold.”

‘A tissue-engineered uterus supports live births in rabbits’ by Renata S. Magalhaes et al. was published in Nature Biotechnology at 16:00 UK time on Monday 29 June 2020.

DOI: 10.1038/s41587-020-0547-7

Declared interests

Dr Douglas Gibson: “None to declare.”

Prof Darren Griffin: “No COI.”

Prof Dusko Ilic: “I declare no conflict of interest.”

Prof Gudrun Moore: “I have no conflicts of interest.”

Prof John Hunt: “Strategic Research theme lead for Medical Technologies and Advanced Materials and the Academic lead for Medical Technologies Innovation Facility (MTIF).”