Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation.

Cell stem cell 2023 Sep 07

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Heterologous organ transplantation is an effective way of replacing organ function but is limited by severe organ shortage. Although generating human organs in other large mammals through embryo complementation would be a groundbreaking solution, it faces many challenges, especially the poor integration of human cells into the recipient tissues. To produce human cells with superior intra-niche competitiveness, we combined optimized pluripotent stem cell culture conditions with the inducible overexpression of two pro-survival genes (MYCN and BCL2). The resulting cells had substantially enhanced viability in the xeno-environment of interspecies chimeric blastocyst and successfully formed organized human-pig chimeric middle-stage kidney (mesonephros) structures up to embryonic day 28 inside nephric-defective pig embryos lacking SIX1 and SALL1. Our findings demonstrate proof of principle of the possibility of generating a humanized primordial organ in organogenesis-disabled pigs, opening an exciting avenue for regenerative medicine and an artificial window for studying human kidney development. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Jiaowei Wang, Wenguang Xie, Nan Li, Wenjuan Li, Zhishuai Zhang, Nana Fan, Zhen Ouyang, Yu Zhao, Chengdan Lai, Hao Li, Mengqi Chen, Longquan Quan, Yunpan Li, Yu Jiang, Wenqi Jia, Lixin Fu, Md Abdul Mazid, Yanling Zhu, Patrick H Maxwell, Guangjin Pan, Miguel A Esteban, Zhen Dai, Liangxue Lai. Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation. Cell stem cell. 2023 Sep 07;30(9):1235-1245.e6