Interspecies chimerism is a phenomenon of an organism consisting of tissue and genetic information from two different species. Currently, many researchers look into the use of interspecies chimerism with human pluripotent stem cells (hPSCs) to generate functional human cells, tissues or organs in large animals, which is expected to solve the problem of the shortage of functional tissues and organs. However, hPSCs interspecies chimerism faces large barriers due to the extremely low chimeric contribution of hPSCs.
Recently, research teams led by Prof. PAN Guangjin and Prof. LAI Liangxue from the Guangzhou Institutes of Biomedicine and Health (GIBH) of Chinese Academy of Sciences (CAS) made new progress on hPSCs interspecies chimerism. This work developed an enhanced hPSCs in interspecies chimerism that allows to obtain functional human blood cells through interspecies chimerism technology for the first time. The related results were published online on April 14, 2022 in Stem Cell Reports.
The teams discovered that the rapid apoptosis of hPSCs in the interspecies embryos was mainly due to the growth disadvantage and a “loser” state competing with the host animal stem cells. A new factor MYCN combined with anti-apoptotic gene BCL2 effectively overcame apoptosis of hPSCs and markedly promoted chimerism formation. Strikingly, the teams isolated live human blood progenitor cells from blood-deficient mice through interspecies chimerism using hPSCs for complementation. The obtained cells can be further cultured and differentiated into different blood cells in dish.
This work presents an important mechanism to understand the interspecies chimerism barrier using hPSCs. The enhanced hPSCs for interspecies chimerism lays a significant foundation for acquiring human cells, tissues and organs for transplantation purposes in the future.
This research was funded by the Strategic Pilot Project of CAS, the National Key Research and Development Program, the National Natural Science Foundation, and the Science and Technology Program of Guangdong Province. The interspecies chimerism experiments using hPSCs have been approved by the Ethnical Committee on Animal Experiments at GIBH. Also, all the experiments were performed according to ISSCR guidelines.
Obtaining Functional Human Blood Cells via Interspecies Chimerism (Image by GIBH)
Pan Guangjin, Ph.D Principal Investigator
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Guangzhou, China, 510530