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从 到 :微流控芯片中鼠胚肾的异种移植和血管化。

From to : xenotransplantation and vascularization of mouse embryonic kidneys in a microfluidic chip.

机构信息

Microfluidics and Biosensor Research Group, Disease Networks Research Unit, Department of Biochemistry and Molecular Medicine, University of Oulu, Finland.

Developmental Biology Laboratory, Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.

出版信息

Lab Chip. 2024 Oct 9;24(20):4816-4826. doi: 10.1039/d4lc00547c.

DOI:10.1039/d4lc00547c
PMID:39290081
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11408908/
Abstract

Organoids are emerging as a powerful tool to investigate complex biological structures . 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 microfluidic approaches have only provided initial vascularization of kidney organoids, whereas 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 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 conditions, the vasculature inside the organoids was successfully maintained. To our knowledge, this is the first demonstration of the combination of and approaches applied to microfluidic chip design.

摘要

类器官正在成为研究复杂生物结构的有力工具。类器官的血管化对于重现所代表的人类器官的形态和功能至关重要,特别是在肾脏的情况下,其主要的血液过滤功能与血液循环密切相关。目前的微流控方法仅为肾类器官提供了初步的血管化,而由于伦理问题,将其移植到动物模型中是有问题的,除了异种移植到鸡胚绒毛尿囊膜(CAM)上。虽然 CAM 可以作为血管化的良好环境,但它只能在一定的时间内使用,受胚胎发育的限制。在这里,我们提出了一种新颖的芯片设计,允许不同来源的类器官在 CAM 上培养和血管化,并在需要时转移到其他条件下。在 CAM 上培养的小鼠胚胎肾脏通过内在的内皮细胞显示出增强的血管化,并与鸡的血管系统建立了联系,这可以通过血液流经它们来证明。在将芯片转移到其他条件下后,类器官内的血管系统成功地得到了维持。据我们所知,这是首次将和微流控芯片设计的应用相结合的演示。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/1e4019cc6425/d4lc00547c-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/b4c1c675e791/d4lc00547c-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/7e7d6012be73/d4lc00547c-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/10c908dff16c/d4lc00547c-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/bbc9eaf7e104/d4lc00547c-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/e61a8eb30dd2/d4lc00547c-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/e721ef4199e5/d4lc00547c-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/1e4019cc6425/d4lc00547c-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/b4c1c675e791/d4lc00547c-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/7e7d6012be73/d4lc00547c-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/10c908dff16c/d4lc00547c-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/bbc9eaf7e104/d4lc00547c-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/e61a8eb30dd2/d4lc00547c-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/e721ef4199e5/d4lc00547c-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d0/11408908/1e4019cc6425/d4lc00547c-f7.jpg

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Lab Chip. 2024 Oct 9;24(20):4816-4826. doi: 10.1039/d4lc00547c.
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