From ex ovo to in vitro: xenotransplantation and vascularization of mouse embryonic kidneys in a microfluidic chip

Micaela Oliveira, Partha Protim Sarker, Ilya Skovorodkin, Ali Kalantarifard, Tugce Haskavuk, Jonatan Mac Intyre, Elizabath Nallukunnel Raju, Samin Nooranian, Hiroki Shioda, Masaki Nishikawa, Yasuyuki Sakai, Seppo J. Vainio*, Caglar Elbuken*, Irina Raykhel*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Organoids are emerging as a powerful tool to investigate complex biological structures in vitro. Vascularization of organoids is crucial to recapitulate the morphology and function of the represented human organ, especially in the case of the kidney, whose primary function of blood filtration is closely associated with blood circulation. Current in vitro microfluidic approaches have only provided initial vascularization of kidney organoids, whereas in vivo transplantation to animal models is problematic due to ethical problems, with the exception of xenotransplantation onto a chicken chorioallantoic membrane (CAM). Although CAM can serve as a good environment for vascularization, it can only be used for a fixed length of time, limited by development of the embryo. Here, we propose a novel lab on a chip design that allows organoids of different origin to be cultured and vascularized on a CAM, as well as to be transferred to in vitro conditions when required. Mouse embryonic kidneys cultured on the CAM showed enhanced vascularization by intrinsic endothelial cells, and made connections with the chicken vasculature, as evidenced by blood flowing through them. After the chips were transferred to in vitro conditions, the vasculature inside the organoids was successfully maintained. To our knowledge, this is the first demonstration of the combination of in vivo and in vitro approaches applied to microfluidic chip design.

Original languageEnglish
Pages (from-to)4816-4826
Number of pages11
JournalLab on a Chip
Volume24
DOIs
Publication statusPublished - 2 Sept 2024
MoE publication typeA1 Journal article-refereed

Keywords

  • Animals
  • Mice
  • Lab-On-A-Chip Devices
  • Kidney/blood supply
  • Transplantation, Heterologous
  • Chorioallantoic Membrane
  • Neovascularization, Physiologic
  • Organoids/cytology
  • Chick Embryo
  • Chickens

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