Assessment of synthetic red cell therapy for extremely preterm ovine fetuses maintained on an artificial placenta life-support platform

Haruo Usuda, Masatoshi Saito, Hideyuki Ikeda, Shinichi Sato, Yusaku Kumagai, Yuya Saito, Shinichi Kawamura, Takushi Hanita, Hiromi Sakai, Shigeo Kure, Nobuo Yaegashi, John P. Newnham, Matthew W Kemp, Shimpei Watanabe

Research output: Contribution to journalArticlepeer-review


Background: Artificial placenta therapy (APT) is an experimental care strategy for extremely preterm infants born at 21–24 weeks’ gestation. In our previous studies, blood taken from the maternal ewe was used as the basis of priming solutions for the artificial placenta circuit. However, the use of maternal blood as a priming solution is accompanied by several challenges. We explored the use of synthetic red cells (hemoglobin vesicles; HbV) as the basis of a priming solution for APT used to manage extremely early preterm ovine fetuses. Methods: Six ewes with singleton pregnancies at 95 d gestation (term = 150 d) were adapted to APT and maintained with constant monitoring of key vital parameters. The target maintenance period was 72 h in duration. A synthetic red cell solution consisting of HbV, sheep albumin and electrolytes was used as priming solutions for the APT circuit. Fetuses were evaluated on gross appearance, physiological parameters and bleeding after euthanasia. Results: Two out of six APT fetuses were successfully maintained for the targeted 72 h experimental period with controllable anemia (>10 g/dl) and methemoglobinemia (<10%) using an infusion of blood transfusion and nitroglycerin delivered >1 h after APT commencement, a sufficient period of time to cross-match blood products and screen for viral agents of concern. Conclusions: Extremely preterm sheep fetuses were maintained for a period of up to 72 h using APT in combination with circuit priming using a synthetic red cell (HbV) preparation. Although significant further refinements are required, these findings demonstrated the potential clinical utility of synthetic blood products in the eventual clinical translation of artificial placenta technology to support extremely preterm infants.

Original languageEnglish
Pages (from-to)653-665
Number of pages13
JournalArtificial Organs
Issue number4
Publication statusPublished - 2022 Apr


  • artificial placenta
  • ex-vivo uterine environment therapy
  • extremely preterm infants
  • hemoglobin vesicles
  • premature lamb
  • synthetic red cells

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering


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