Artificial womb or placenta? Research goes back to the 50s


Last week, French media strongly echoed an American publication describing the development of premature lambs in an “artificial womb”. For Gènéthique, Jacques Suaudeau provided an analysis of the announcement, replacing it in its rightful context.  He believes “we are still ages away from an “artificial womb”.

 

First, what we have is not an “artificial womb” but an “artificial placenta” which can help only once the foetus has reached its final size because of the cannulation problems with the umbilical vessels. Besides, it is only a short-term solution because the system is prone to bacteria contamination.

 

The first attempts at using a foetal extracorporeal perfusion system, to insure a foetus’ survival goes back to the 50s. In 1958, Westin and his colleagues described an extracorporeal perfusion system for human foetuses[1]. Then, in 1965, Callaghan’s team tried to connect the umbilical vessels of lamb foetuses to an oxygen exchanger, inside an arterial-venous system, but without much success[2].

 

Progress was made in 1969 with the invention of the “ECMO” technique, an extracorporeal oxygenation system using a membrane oxygenator. Thanks to this circuit, two researchers, Zapol and Kolobow, maintained sheep foetuses alive for 55 hours[3]. Later on, the question presented less of an interest as the treatment for respiratory distress of new-born babies had progressed thanks to the administration of steroids, ventilation, and surfactants.

 

In 1979, Griffith and his team went back to this field of research [4]. In the 80s, a group led by Doctor Yoshinori Kuwabara carried out a series of experiments on artificial placentas, using Zapol and Kolobow’s framework as well as extracorporeal oxygenation[5]. They managed to keep the foetus alive for 165 hours. By modifying the incubator system in which the foetus was put, they managed to achieve 146 hours, and then 236 hours of survival  in 1989[6]. The difficulties that arose during these experiments led researchers to developing an extracorporeal artery-venous oxygenation circuit, without a pump, using the strength of the foetus’ heart to get the blood moving  through the respirator [7].  In 2015, Bryner’s team managed to keep the foetus alive for a whole week thanks to a device similar to the one used by Zapol and Kolobow[8].

 

The device recently described by Partridge and al (2017, AW Flake lab) uses a framework developed by Miura and his team in 2012[9] : no pump, the foetus’ heart sends the blood to the membrane oxygenator. They improved the “amniocentesis” in which the foetus lies to make it impervious to infectious agents. Indeed, infections were a problem to Zapo and Kolobow, but also because they had performed a non-sterile intervention. These improvements enabled Partridge’s team to extend the extra-uterine survival time to four weeks.

 

Such a device could be used for highly premature babies, but could provoke respiratory disorders because of a lack of surfactant. A lot of experimental work will be necessary before being able to insure the system is safe. If, because of a lack of surfactant, there really was a strong respiratory discomfort in the premature new-born baby, and that medical treatment didn’t seem to work, it would always be possible to put the premature new-born baby in ECMO after birth; a less risky option for the foetus than before birth.

 

Partidge and al’s results show clear progress but it is too soon to speak of a revolution: the success lies in the perfusion method used by Zapol and Kolobow.

 

Photo : Pixabay/DR

 

[1] Westin B, Nyberg R, Enhorning G. A technique for perfusion of the previable human fetus. Acta Paediatrica, July 1958, vol.;47, n°4, pp.339-349.

[2] Callaghan jc, Maynes ea, Hug hr., Studies on lambs of the development of an artificial placenta. review of nine long-term survivors of extracorporeal circulation maintained in a fluid medium. Canadian Journal of Surgery, April 1965, vol.8, pp.208-213.

[3] Doppman JL, Zapol W, Kolobow T, Pierce J. Angiocardiography of fetal lambs on artificial placenta. Investigative Radiology, May-June 1970, vol.5, n°3, pp.181-186.

 Zapol WM, Kolobow T, Pierce JEVUREK GG, Bowman RL. Artificial placenta: two days of total extrauterine support of the isolated premature lamb fetus, Science, 31 October 1969, vol.166, n°3905, pp.617-618.

[4] Griffith BP, Borovetz HS, Hardesty RL, Hung TK, Bahnson HT. Arteriovenous ECMO for neonatal respiratory support. A study in perigestational lambs. The Journal of Thoracic and Cardiovascular Surgery, April 1979, vol.77, n°4, pp.595-601.

[5] Kuwabara Y, Okai T, Imanishi Y, Muronosono E, Kozuma S, Takeda S, Baba K, Mizuno M. Development of extrauterine fetal incubation system using extracorporeal membrane oxygenator. Artificial Organs, June 1987, vol.11, n°3, pp.224-227.

[6] Kuwabara Y, Okai T, Kozuma S, Unno N, Akiba K, Shinozuka N, Maeda T, Mizuno M. Artificial placenta: long-term extrauterine incubation of isolated goat fetuses. Artificial Organs, December. 1989, vol.13, n°6, pp.527-531.

[7] Awad JA, Cloutier R, Fournier L, Major D, Martin L, Masson M, Guidoin R., Pumpless respiratory assistance using a membrane oxygenator as an artificial placenta: a preliminary study in newborn and preterm lambs, Journal of Investigative Surgery, Jan-Feb 1995 vol.8, n°1, pp.:21-30.

Arens J, Schoberer M, Lohr A, Orlikowsky T, Seehase M, Jellema RK, Collins JJ, Kramer BW, Schmitz-Rode T, Steinseifer U., NeonatOx: a pumpless extracorporeal lung support for premature neonates, Artificial Organs, November 2011, vol.35, n°11, pp.997-1001.

[8] Bryner B, Gray B, Perkins E, Davis R, Hoffman H, Barks J, Owens G, Bocks M, Rojas-Peña A, Hirschl R, Bartlett R, Mychaliska G., An extracorporeal artificial placenta supports extremely premature lambs for 1 week.

Journal of Pediatric Surgery, January 2015, vol.50, n°1, pp.44-49.

[9] Miura Y, Matsuda T, Funakubo A, Watanabe S, Kitanishi R, Saito M, Hanita T,. Novel modification of an artificial placenta: pumpless arteriovenous extracorporeal life support in a premature lamb model, Pediaticr Research, November 2012, vol.72, n°5, pp.490-494.