TL;DR
Researchers from Guangzhou Institutes of Biomedicine and Health have successfully grown humanized kidneys in pig embryos for the first time. The study, published in Cell Stem Cell, used a three-step technique to overcome previous challenges in interspecies chimeras. While the long-term goal is human organ transplantation, the immediate applications include studying human organ development and diseases. Stem cell research and CRISPR technology is continuing to lead to new and more impressive achievements.
Living the Dream
It has long been the dream to produce human organs from other animals with pigs being the likely best “donor”. After years of high hopes and hard work, scientists at Guangzhou Institutes of Biomedicine and Health have achieved a groundbreaking feat by successfully growing kidneys with human cells inside pig embryos. This marks the first instance of a solid human organ being cultivated within another species. The study was published on September 7 in the journal Cell Stem Cell.
The team chose kidneys for their experiment because they are among the first organs to form and are the most frequently transplanted human organs. Previous attempts to grow human organs in pigs had failed due to challenges in integrating human cells into pig tissues.
The researchers, led by senior authors Liangxue and Guangjin Pan, developed a novel approach to improve the efficiency of interspecies chimeras. They identified key factors that would help human cells better integrate into pig tissues.
The methodology involved three crucial steps:
Using CRISPR technology, the team genetically modified a single-cell pig embryo to lack two essential genes for kidney development, creating a “niche” for human cells.
They then manipulated human pluripotent stem cells to be more receptive to integration and less prone to self-destruction. These cells were converted into “naïve” cells resembling early human embryonic cells.
Before implantation, the embryos were cultivated in conditions tailored to meet the unique needs of both human and pig cells.
In total, 1,820 embryos were implanted into 13 surrogate pig mothers. The pregnancies were terminated after 25 or 28 days to evaluate the success of the experiment. Five chimeric embryos were analyzed and found to have structurally sound kidneys, composed of 50-60% human cells.
The researchers also examined the ethical implications by checking if human cells had migrated to other tissues in the embryos. They found that human cells were primarily localized to the kidneys, minimizing ethical concerns.
Senior author Zhen Dai stated, “Creating a niche in the pig embryo allows human cells to naturally occupy these spaces.” The team is now planning to extend the development period of these kidneys and is also exploring the possibility of growing other human organs like the heart and pancreas in pigs.
While the ultimate aim is to use this technology for human organ transplants, the researchers admit that achieving this goal will be complex and time-consuming. In the interim, the technique offers a valuable platform for studying human organ development and diseases.
References
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; 30 (9): 1235 DOI: 10.1016/j.stem.2023.08.003