The research team of Professor Pan Guangjin and Professor Lai Liangxue from the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences has made new progress in their collaborative research on human pluripotent stem cell (hPSC) interspecies chimera. They used the hPSC interspecies chimera technology in mouse and successfully obtained functional human-derived blood cells for the first time. The results were published on April 14 in the ISSCR journal Stem Cell Reports under the title "Generating Functional Cells Through Enhanced Interspecies Chimerism with Human Pluripotent Stem Cells".
Generating functional human cells, tissues, or organs within large animal hosts, such as pigs, using human pluripotent stem cell (hPSC) interspecies chimerism is a promising approach to address the critical shortage of transplantable tissues and organs. However, there are major obstacles and low efficiency in hPSC interspecies chimerism, which has severely hindered the progress in this field. The research team of Professor Pan Guangjin systematically studied the mechanism of these barriers. Their previous research found that the apoptosis of hPSCs in the early stages of interspecies embryos is an important factor hindering interspecies chimerism, and that BMI1 can improve the efficiency of hPSC chimerism in mouse, rabbit and pig embryos by inhibiting the apoptosis of hPSCs.
Based on this, the team further found that during the interspecies chimerism process, hPSCs are at a growth disadvantage compared to the host stem cells and undergo apoptosis during the cooperative differentiation process. They discovered a new factor, MYCN, which can effectively overcome the disadvantage and apoptosis of hPSCs in interspecies chimerism and significantly promote their interspecies chimeric ability. They further used a blood-deficient mouse model and isolated human blood stem/progenitor cells with good activity and continuous culture/differentiation potential from the chimeric embryos, demonstrating the feasibility of obtaining functional human-derived cells through interspecies chimerism. This lays the foundation for future acquisition of human cells, tissues and organs for transplantation.
This research was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences, the National Key Research and Development Program of China, the National Natural Science Foundation of China, and the Science and Technology Program of Guangdong Province. The research has undergone relevant ethical review and complies with ethical standards.
The Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences has made important progress in human pluripotent stem cell (hPSC) interspecies chimerism technology.
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