In the race to develop assisted reproduction and stem cell-related technologies to save the northern white rhino from extinction, the BioRescue consortium announces a major breakthrough: the creation of primitive germ-like cells (PGCLSs) from induced pluripotent stem cells of the northern white rhino. rhino Nabire. This milestone was led by experts from Osaka University in Japan and has never been achieved before in large mammals. There is one final step you need to master in producing artificial rhino gametes (eggs and sperm) from preserved tissue. If successful, this will increase the availability and genetic diversity of embryos and will be a cornerstone for saving the northern white rhino. The scientists describe culture systems and processes for the induction of PGCLCs from stem cells in a paper just published in the journal Science. Science Advances.
Thirty-three-year-old Najin and her daughter Fatu are the last surviving northern white rhinos on the planet. With only two females of its kind left, the northern white rhino’s only hope lies in advanced assisted reproductive technologies. Scientists of the BioRescue consortium have already produced northern white rhino embryos through in vitro fertilization of oocytes with sperm. The embryos will be born by southern white rhino surrogate mothers. Very important for embryo production is the availability of oocytes (egg cells) and sperm. The female Fatu is the only donor of the remaining natural oocytes and only four males have frozen sperm in the program – and some of these males are closely related to Fatu. BioRescue scientists aim to overcome this bottleneck with stem cell-associated techniques (SCAT): Using the stored and preserved tissue of rhino skin, it should in principle be possible to generate induced pluripotent stem cells (iPCSs), primitive germ cells, and finally artificial gametes. This could increase the number of individuals in the founding group of a future population to 12 and allow for the production of much larger quantities of oocytes. According to their most recent paper published in the journal “Science Advances,” the team has now successfully grown primitive germ cells (PGCs) from embryonic stem cells (ESCs) and induced pluripotent stem cells (predecessors of egg and sperm). iPSCs).
In sexually reproducing organisms like humans, rhinos or mice, primitive microbes next. In order to develop from stem cells, they need a very specific environment in which signals from hormones or proteins trigger the necessary morphological and functional transformation. This also includes the migration of cells throughout the body (PGC migration). BioRescue scientists Masafumi Hayashi and Katsuhiko Hayashi and their team from Osaka University have succeeded in creating such an environment in a culture system for the first time in large mammals. They set up culture systems for the southern white rhino, where embryonic stem cells are available, and for the northern white rhino, where they used induced pluripotent stem cells derived from tissue samples. To be successful, they needed to identify the signals that should be delivered to the system at certain time points and the order in which they should trigger the development of PGCLCs.
The scientists relied on information from the mouse model: In 2016, Katsuhiko Hayashi and her team were able to create primitive germ-like cells and finally germ cells from mice that were fertilized in the lab, resulting in healthy offspring. In the case of white rhinos, Hayashi works closely with Sebastian Diecke’s Pluripotent Stem Cells Platform at the Max Delbrück Center at BioRescue and reproduction specialists Thomas Hildebrandt of Leibniz-IZW, both of the paper’s recent authors and Cesare. Welsh from Avantea.
The BioRescue team produced PGCLCs from the northern white rhino, Nabire, under a defined condition, through repeated remediation. As PGCs are the constitutive population of gametes, this achievement opens up a way to generate functional gametes from induced pluripotent stem cells of northern white rhinos, which will contribute to the effort to rewind their extinction. Once the creation of artificial gametes is successful, this plan combines with BioRescue’s procedures for natural gametes: Just like oocytes from Fatu and thawed sperm from frozen samples, the artificially created eggs and sperm are fertilized in vitro. in the laboratory. Embryos created in this way will be safely stored in liquid nitrogen until transfer to the surrogate mother is possible.
The southern white rhino embryonic stem cells used in Japan come from the Avantea lab in Cremona, Italy, where it was grown by Cesare Galli’s team. The newly derived northern white rhino PGCs, meanwhile, originated from the skin cells of Fatu’s aunt Nabire, who died in 2015 at Safari Park Dvůr Králové in the Czech Republic. Sebastian Diecke’s team at the Max Delbrück Center was responsible for transforming them into induced pluripotent stem cells.
All BioRescue procedures are accompanied by ethical risk assessments conducted under the guidance of the Ethics Laboratory for Veterinary, Conservation and Animal Welfare at the University of Padua, Italy.
materials provided by Leibniz Zoo and Wildlife Research Institute (IZW). Note: Content can be edited for style and length.