The Wake Forest Institute for Regenerative Medicine (WFIRM) has announced that uterine tissue made from bioengineering technology can successfully repair a rabbit’s uterus and produce a living offspring. Although the study produced only part of the uterine tissue and did not produce the entire uterus, the team hopes to replace uterine transplants with this technology in the future, but the prospect of the application is clearly controversial.
In 2011, Anthony Atala, M.D., lead researcher and director of WFIRM research, presented artificially bred kidneys at the TED conference. Photo: Wikipedia
Today, Nature-Biotechnology published a study announcing that the “artificial womb” repaired using bioengineering technology has allowed rabbits to produce surviving offspring.
The study was carried out by the Wake Forest Institute for Regenerative Medicine (WFIRM). The team inoculated the experimental animals’ own cells into biodegradable stents and cultured them to show that the bioengineered uterus can develop natural tissue-like structures that support normal reproductive function.
For more than two decades, the team has invented artificial bladders, artificial vaginas and urethras, and this time they hope the technology will eventually replace uterine transplants, giving women with uterine dysfunction a chance to give birth. However, it is worth noting that artificial organs as a whole have not yet entered large-scale clinical applications, and with the artificial uterine technology is maturing, this ethical dispute will become a problem that can not be ignored.
Custom-made wombs for rabbits
In this study, the team randomly divided the rabbit into four groups: (1) tissue engineering uterine group, implanted with the animal’s own cells after the removal of part of the uterus, implanted with the animal’s own cells inoculation stents;
Rabbits have long been used in reproductive biology research and are ideal for uterine tissue regeneration because their uteruses are relatively large compared to other experimental animals. The female rabbit’s uterus consists of two separate uterine corners and a cervix, each with the ability to make a pregnancy. In this experiment, one side of the uterus was completely removed from one side of the three experimental groups and the uterine corner on the other side was partially removed.
Biodegradable polymer stent constructs are individually customized for each animal. The researchers extracted cells from each rabbit’s uterine structure to grow regenerative uterine tissue and inoculate the stents. Six months after the stent implant surgery, the rabbit mates naturally with the male rabbit that can be bred.
Experiments showthat that after 6 months of implantation, tissue engineered uterine develops structures similar to those of natural tissue, including the epithelial and adenosic epithelial, mucous membranes with blood vessels, and double uterine muscle layers. In the three experimental groups, only rabbits implanted with cell-inoculated stents successfully became pregnant, gave birth in full-term months and gave birth to surviving offspring.
A bioengineered genetically modified ct image of the rabbit’s uterus, in which a fetus is conceived. Photo credit: Wake Forest Institute for Regenerative Medicine (WFIRM)
“Research shows that engineered uterine tissue can support a normal pregnancy and allow the fetus to develop normally, and that the size and weight of the offspring is comparable in size and weight to that of a normal uterine fetus,” said Anthony Atala, M.D., lead researcher and director of WFIRM research. With further improvements, this method may help women with uterine abnormalities become pregnant. “
The road to research and development of artificial organs
About 6% of women who are treated with infertility suffer from uterine dysfunction. The researchers say they are planning further preclinical studies to prepare for future clinical trials. They hope this method will eventually replace uterine transplants that rely on organ donation. So far, only about 70 uterine transplants have been performed worldwide, and fewer than 10 babies have been born in the United States through transplants. The bioengineering technique, which uses the patient’s own cells to create uterine tissue, not only eliminates dependence on organ donation, but also avoids the risk of rejection.
The WFIRM team has a long history of manufacturing organs using 3D printing, tissue engineering, and more. Atala himself is a urologist, and as early as 1999 he led the team to complete the first artificial organ transplant, replacing seven patients with bladders grown from their own cells. The team then invented artificial vaginas and male urethras for small-scale clinical trials. In 2008, they made artificial penises that were successful in the rabbit model, and all 12 rabbits in the experimental group tried mating, eight of them completed mating, and four successfully conceiveed and gave birth to cubs.
Next, The Atala team began experimenting with the manufacture of organs such as kidneys and hearts, and conducted organ-like studies. In 2016, they published a report in Nature Biotechnology that used a complex, specially tailored 3D printer that prints out ears, bones and muscle structures to replace injured or diseased tissue. In March, the team announced the invention of a chip with multiple types of organ tissue that can be used to quickly detect the toxicity of candidate drugs to humans, the paper was published in Biomanufacturing.
Photo credit: The Guardian
Of course, there is still a long way to go between animal models and human clinical trials. Douglas Gibson, a researcher at the University of Edinburgh, commented: “One of the core differences (in humans and rabbits) is that humans have spontaneous ovulation and menstrual cycles, and the uterus has periodic changes in the process, but rabbits do not have menstrual cycles. This difference is likely to have an impact when trying to develop artificial human uteruss in a similar way. Gibson was not involved in the study.
And it is important to note that the artificial organ technology of the Atala team as a whole has not been widely used. “While the results of these clinical studies (artificial bladder, etc.) have been satisfactory so far, none of these techniques are significantly better than current standards of care or fully meet their expectations,” said Dusko Ilic, professor of stem cell science at King’s College London. It is also in urgent need of many improvements to replace traditional surgical reconstructive techniques and make tissue engineering cost-effective and risk-free for patients. Ilik was also not involved in the study.
Ethical Controversy of Artificial Wombs
Artificial wombs face much more ethical controversy than other artificial organs. In April 2017, the team at Children’s Hospital of Philadelphia announced that the survival of ultra-premature lambs was maintained with an external artificial uterus, setting a new record for in vitro survival time for embryos. If this kind of device can be applied to the clinic, it will greatly improve the survival rate of premature babies. Thus, in October 2019, the EU Horizon 2020 Program allocated 2.9 million euros (approximately RMB23.2 million) to support the study of artificial uteruses.
While current in vitro artificial wombs are being studied to save super-premature babies, the sight of lambs wrapped in transparent devices has also caused some unease, reminiscent of scenes in “The Hacking Empire.” Some scholars have pointed out that the practical application of such technology may exceed expectations, for example, if the technology is shown to save premature babies at 23 to 24 weeks of pregnancy, then parents and doctors may try to use it to care for a more premature fetus;
The same is true of the recently published artificial uterine tissue implanted in the body. Although its original intention was to provide women with uterine diseasewho who wish to have offspring of organ transplantation, it will also encounter more practical problems at the application level and may lead to more discussion in the future.