Continued Efforts to Produce Universal Pluripotent Stem Cells
Publicity materials here note a recent research initiative to produce pluripotent stem cell lines that will not be rejected when transplanted into other individuals, or even between species. This technological capability is necessary to the development of new forms of regenerative medicine, allowing the production of universal donor cells and tissues at reasonable cost. While the results sound impressive, it is worth noting that several large and well-funded pharma companies have been developing earlier, first generation versions of this technology for some years, accompanied by many smaller research groups and companies. A number of different approaches have been tried, but the broader goal of their use in cell therapies and tissue engineering remains challenging and expensive under the present system of medical regulation. Progress is slow and painstaking, and it remains unclear as to whether regulators consider this technology even in principle safe enough for the clinic, after years of intense investment. The approach noted here will still encounter these issues if it is further developed.
Pluripotent stem cells can turn into any type of cell in the body. The findings offer a viable path forward for pluripotent stem cell-based therapies to restore tissues that are lost in diseases such as Type 1 diabetes or macular degeneration. "There has been a lot of excitement for decades around the field of pluripotent stem cells and regenerative medicine. What we have learned from the experiences of organ transplantation is that you have to have matched donors, but the person receiving the transplant often still requires lifelong immune suppression, and that means there is increased susceptibility to infections and cancer. We've been trying to figure out what it is that you need to do to those stem cells to keep them from getting rejected, and it looks like we have a possible solution."
To test their hypothesis, researchers used CRISPR-Cas9 technology, "genetic scissors" that allow scientists to make precise mutations within the genome at extremely specific locations. Using human pluripotent stem cells, the team located the specific genes they believed were involved in immune rejection and removed them: β2M, TAP1, CIITA, CD74, MICA, and MICB. Prior research into pluripotent stem cells and immune rejection looked at different parts of the immune system in isolation. The researchers instead opted to test their genetically modified stem cells in a complete and functional immune system.
"Transplantation across species, across the xenogeneic barrier, is difficult and is a very high bar for transplantation. We decided if we could overcome that barrier, then we could start to have confidence that we can overcome what should be a simpler human-to-human barrier, and so that's basically what we did." The research team tested the modified human stem cells by placing them into mice with normal, fully functioning immune systems. The results were promising - the genetically engineered pluripotent stem cells were integrated and persisted without being rejected.