A newly discovered type of stem cell may allow human organ tissue to be grown inside large animals for research and therapeutic applications. A team of developmental biologists at the Salk Institute for Biological Sciences in La Jolla, California apparently stumbled upon the yet unknown genre of stem cell while seeking to implant human stem cells into mouse embryos. The research was published in last week’s issue of Nature. “I found the paper fascinating,” said George Daley, a stem cell biologist at Children’s Hospital Boston and Harvard Medical School. “It highlights a new type of pluripotent stem cell, which is among the most exciting aspects of stem cell biology over the last several years.”
Stem cells are classified by the unique ability to differentiate into any type of tissue – this is known as pluripotency. As reported in Nature, Juan Carlos Izpisua Belmonte (a developmental biologist at the Salk Institute) and his colleagues tell of a new type of pluripotent cell, which is easier to grow in the lab and also graft into embryos. The team refers to this kind of cell as a ‘region-selective pluripotent stem cell (rsPSC)’.
Initially, Izpisua Belmonte and his team were attempting to transplant already known types of human stem cells into mouse embryos in vitro. For each attempt, cells were grown up in media containing varieties of growth factors and chemicals. In particular, one combination helped the cells thrive and proliferate. When this was investigated, the team discovered that the stem cell displayed different patterns of metabolism and gene expression compared to other pluripotent cells and they were more challenging to graft to the mouse embryo. “We believe that [rsPSCs] should have the ability to differentiate more efficiently into somatic cells . . . because they are right at the junction of pluripotency and differentiation,” said study coauthor Jun Wu, a research associate in the Belmonte lab.
The next step was reportedly to investigate what might help this cell-type’s ability to graft. So, the researchers injected these cells into three different regions of a young mouse embryo. A day-and-a-half later they found that only cells that were injected into the tail or rear of the embryo were able to integrate. This created a ‘chimaeric embryo’ – an organism with varying DNA origins. Therefore, since these cells seemed to prefer a certain area of the embryo, the team coined them as region-selective.
Izpisua Belmonte speculates that developing embryos might contain several kinds of pluripotent stem cells, including rsPSCs. However, their precise part in development remains elusive for now. Nevertheless, understanding their role more deeply may allow biologists to study the early embryonic stages of development by transplanting human embryonic stem cells into animal embryos.
Following that, the researchers decided to use enzymes to edit the genomes of the rsPSCs. Gene editing in this way might help biologists to grow human cells inside of other species’ and produce transgenic chimaeras. Paul Tesar, a developmental biologist at Case Western Reserve University in Cleveland, Ohio, explains that this may be challenging considering that it is unknown whether the animal’s immune system may passively accept the rsPSCs or if the immune system may react to it. Belmonte too reportedly understands these concerns and adds that there may be ethical questions to ask for gene editing and creating human-animal hybrids. The lab is currently aiming to work on implanting pig embryos with human stem cells.
According to Tesar, because these region-selective cells grow much more quickly and stably than other pluripotent cells, they may be even more useful in developing new therapies. Stem cells have already been trialled and used in a variety of clinical research, such as growing spinal cord-like tissue from scratch, and are a valuable cell source for regenerative medicine techniques. “That changing culture conditions [may] generate different kinds of stem cells is [unsurprising],” said Paul Knoepfler, a stem cell biologist at the University of California, Davis. “[However] it is exciting. I expect that more new cell types [might] be found in the future.”
How might this innovation be efficiently regulated to ensure its safety in clinical use?