Organ transplant rejection might eventually be preventable by giving recipients an immune-suppressing vaccine derived from induced pluripotent stem cells, according to a study led by Japanese researchers.

In mice, the treatment allowed permanent acceptance of heart grafts by selectively inhibiting the immune response to the donor graft, said the study, published April 20 in Stem Cell Reports. The work might also be applicable to autoimmune diseases, the study said.

The study can be found at j.mp/ipscden. The co-first authors were Songjie Cai, Jiangang Hou, and Masayuki Fujino. The senior author was Xiao-Kang Li. All are of the National Research Institute for Child Health and Development in Tokyo.

The IPS cells were matured into donor-type regulatory dendritic cells (DCregs) which in turn caused production of tolerance-inducing regulatory T cells, or Tregs, that allow the graft to be treated as self.

While the technology looks good, a UC San Diego stem cell researcher said it faces a number of hurdles that make practical use of it difficult, especially the difficulty in producing the donor-derived regulatory cells in time to be of use in a transplant.

Use of these Tregs and immature DCregs for transplant has been investigated for several years now. In theory, they would provide a better method of preventing rejection than immunosuppressive drugs that knock down immune functioning across the board.

However, activating Tregs must be done precisely, or other T cell types will be activated, increasing the risk of rejection.

The study found that donor-type dendritic cells reliably activated Tregs and not the other types. Peptide antigens from the graft directed naive CD4+ T cells to mature into donor-specific Tregs, providing a selective immune signal to tolerate the graft.

Use of IPS cells for producing these immune regulatory cells is quite novel, said Dan Kaufman, director of cell therapy at UC San Diego, and affiliated with the universitys Sanford Stem Cell Clinical Center.

Obviously, it fits my interest in making immune cells from ES and IPS cells, Kaufman said. The ability to use these cells to suppress transplant rejection seems quite strong. I think the data is all good.

That said, the findings could be strengthened by extending the work from animals to human xenografts, he said. That would demonstrate that human IPS cells can similarly function, although it would be challenging.

Another limitation is the need to use donor-derived cells to induce immune tolerance.

How you would translate that would be unclear to me, Kaufman said.

Are you going to get a heart and then make IPS cells from that donor, which obviously you couldnt do in a reasonable time frame? Could you create a bank of these types of cells that might be suitable for certain patient populations with certain HLA types? Im not sure. I think that gets a little more speculative.

Another speculative possibility is to make the donor-derived IPS cells grow into an organ, and then also create the immune-regulating cells from these IPS cells to selectively induce tolerance.

But were still, I think, a long ways off from having IPS-derived organs, he said.

Autoimmune disease treatment with this technology is worth exploring, Kaufman said. In that case, the IPSCs would be made from the patients themselves.

More than 118,000 Americans are on the waiting list for an organ transplant, according to the Organ Procurement and Transplantation Network.

bradley.fikes@sduniontribune.com

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Stem cell-based treatment prevents transplant rejection, in animal study – The San Diego Union-Tribune

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