Bioengineered uterine tissue supports pregnancy in a rat model

Mats Hellström, Juan M. Moreno-Moya, Sara Bandstein, Eva Bom, Randa R. Akouri, Kaoru Miyazaki, Tetsuo Maruyama, Mats Brännström

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Objective: To create a bioengineered uterine patch for uterine repair of a partially defect uterus. Design: Three different decellularized uterine scaffolds were recellularized in vitro with primary uterine cells and green fluorescent protein- (GPF-) labeled bone marrow-derived mesenchymal stem cells (GFP-MSCs). The patches were transplanted in vivo to investigate their tissue adaptation and supporting capacity during pregnancy. Setting: Research laboratory. Animal(s): Female Lewis rats (n = 9) as donors to generate whole-uterus scaffolds using three different protocols (n = 3 per protocol); Sprague Dawley rats (n = 40) for primary uterus cell isolation procedures (n = 10) and for transplantation/pregnancy studies (n = 30); and male Sprague Dawley rats (n = 12) for mating. Intervention(s): Decellularization was achieved by whole-uterus perfusion with buffered or nonbuffered Triton-X100 and dimethyl sulfoxide (DMSO; group P1/P2) or with sodium deoxycholate (group P3). Primary uterine cells and GFP-MSCs were used to develop uterine tissue constructs, which were grafted to uteri with partial tissue defects. Main Outcome Measure(s): Recellularization efficiency and graft quality were analyzed morphologically, immunohistochemically, and by real-time quantitative polymerase chain reaction (PCR). The location and number of fetuses were documented during pregnancy days 16-20. Result(s): Pregnancy and fetal development were normal in groups P1 and P2, with fetal development over patched areas. Group P3 showed significant reduction of fetal numbers, and embryos were not seen in the grafted area. Quantitative PCR and immunohistochemistry revealed uterus-like tissue in the patches, which had been further reconstructed by infiltrating host cells after transplantation. Conclusion(s): Primary uterine cells and MSCs can be used to reconstruct decellularized uterine tissue. The bioengineered patches made from triton-X100+DMSO-generated scaffolds were supportive during pregnancy. These protocols should be explored further to develop suitable grafting material to repair partially defect uteri and possibly to create a complete bioengineered uterus.

Original languageEnglish
JournalFertility and Sterility
DOIs
Publication statusAccepted/In press - 2016 Jan 21

Fingerprint

Uterus
Pregnancy
Dimethyl Sulfoxide
Multifetal Pregnancy Reduction
Octoxynol
Fetal Development
Sprague Dawley Rats
Deoxycholic Acid
Cell Separation
Cell Transplantation
Green Fluorescent Proteins
Mesenchymal Stromal Cells
Real-Time Polymerase Chain Reaction
Fetus
Perfusion
Transplantation
Bone Marrow
Immunohistochemistry
Outcome Assessment (Health Care)
Transplants

Keywords

  • Decellularization
  • In vivo
  • Recellularization
  • Tissue engineering
  • Uterus

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Hellström, M., Moreno-Moya, J. M., Bandstein, S., Bom, E., Akouri, R. R., Miyazaki, K., ... Brännström, M. (Accepted/In press). Bioengineered uterine tissue supports pregnancy in a rat model. Fertility and Sterility. https://doi.org/10.1016/j.fertnstert.2016.03.048

Bioengineered uterine tissue supports pregnancy in a rat model. / Hellström, Mats; Moreno-Moya, Juan M.; Bandstein, Sara; Bom, Eva; Akouri, Randa R.; Miyazaki, Kaoru; Maruyama, Tetsuo; Brännström, Mats.

In: Fertility and Sterility, 21.01.2016.

Research output: Contribution to journalArticle

Hellström, M, Moreno-Moya, JM, Bandstein, S, Bom, E, Akouri, RR, Miyazaki, K, Maruyama, T & Brännström, M 2016, 'Bioengineered uterine tissue supports pregnancy in a rat model', Fertility and Sterility. https://doi.org/10.1016/j.fertnstert.2016.03.048
Hellström M, Moreno-Moya JM, Bandstein S, Bom E, Akouri RR, Miyazaki K et al. Bioengineered uterine tissue supports pregnancy in a rat model. Fertility and Sterility. 2016 Jan 21. https://doi.org/10.1016/j.fertnstert.2016.03.048
Hellström, Mats ; Moreno-Moya, Juan M. ; Bandstein, Sara ; Bom, Eva ; Akouri, Randa R. ; Miyazaki, Kaoru ; Maruyama, Tetsuo ; Brännström, Mats. / Bioengineered uterine tissue supports pregnancy in a rat model. In: Fertility and Sterility. 2016.
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