![]() “The reprogramming process even in humans has a low success rate, which can be mitigated by starting with large numbers of cells, and has been the focus of much protocol optimization,” said Marisa Korody, a behavioral geneticist involved in San Diego Zoo’s northern white rhino project. After a little tweaking, they made remarkable progress: seven clones per 100,000 skin cells - a 700% increase in efficiency. At first, they were lucky to get just one stem cell from 100,000 skin cells. ![]() They spent years modifying Yamanaka’s technique so it would work on white rhino skin cells. In 2021, the researchers at San Diego Zoo added northern white rhinos to that list. Since Yamanaka’s discovery, scientists around the world have been studying how to use the Yamanaka factors to reset cells in dozens of animals: mice, humans, monkeys, cats, pigs, horses, chicken, quail, zebra fish, snow leopards, Bengal tigers, jaguars, Tasmanian devils, mink, and even the humble platypus. This earned him a Nobel Prize and kick-started a new age of stem cell and anti-aging reseach. He found only four regulatory molecules (called “ Yamanaka factors”) are necessary for this reset. In 2006, Shinya Yamanaka discovered how to access those genes, essentially resetting and de-programming the skin cell back into a stem cell. Those genes are just inaccessible to the cell. However, though the cells cannot turn into other kinds of cells, the information to do so is still contained in the cell’s genes. The same is true of nerve cells, muscle cells, and any other kind of fully differentiated cell. Once a skin cell is a skin cell, that is the end of the line it will not become any other type of cell. They just have skin cells, which makes things complicated. Theoretically, egg and sperm cells could be created if the researchers had northern white rhino stem cells. Stem cells are the starting point for all other cells, including egg and sperm cells. Step 1: Convert skin cells into stem cells ![]() And yet, in the last three years, the San Diego Zoo scientists have made significant progress on all of thm. However, there is a problem with this strategy: No one knows how to do any of these steps in white rhinos. (4) Transplant the embryo into a womb, where it will develop into a baby rhinoceros. ![]() (3) Fertilize the egg with the sperm to create an embryo. (2) Reprogram those stem cells to become egg and sperm cells. There are four (giant) steps required to create a herd of northern white rhinos from a vial of frozen skin cells: (1) Convert skin cells into stem cells. In that repository, there are skin cells from twelve northern white rhinos, enough genetic diversity to create a sustainable population. As of February 2022, there are a total of fourteen northern white rhino embryos created, 11 from eggs from Fatu inseminated by sperm from Suni and 3 inseminated by sperm from Angalifu.Those skin cells are stored at a special facility within the San Diego Zoo called the Frozen Zoo, which cares for over 10,000 living cell types representing nearly 1,000 animal species. In December 2020, 14 egg cells were retrieved from Fatu eight of them were fertilised by the sperm of the dead northern white rhino Suni, resulting in two viable embryos. In January 2020, it was announced that "another embryo" was created using the same techniques all three embryos are "from Fatu", until they can be placed into a surrogate mother, probably a southern white rhino. In September 2019, scientists announced that they fertilized in vitro the eggs with frozen sperm taken from dead males two of the resulting embryos were viable. In August 2019, ten egg cells (five from Najin and five from Fatu) were harvested to be artificially inseminated with the frozen sperm of a northern white rhino as part of a project by the Leibniz Institute for Zoo and Wildlife Research, Dvůr Králové Zoo, Kenya Wildlife Service, and Avantea. The DNA of a dozen northern white rhinos has been preserved in genetic banks in Berlin and San Diego. Subsequently, in the future, it might be possible to specifically mature the cells into specific cells such as neurons and muscle cells, in a similar way in which Katsuhiko Hayashi has grown mouse oocytes out of simple skin cells. At the end of 2015, scientists from the Leibniz Institute for Zoo and Wildlife Research, San Diego Zoo Global, Tiergarten Schönbrunn, and Dvůr Králové Zoo developed a plan to reproduce northern white rhinos using natural gametes of the living rhinos and induced pluripotent stem cells.
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