Advertisement
Research associate Jason Reed performs cell culture maintenance in the Sacha lab, at the OHSU Vaccine and Gene Therapy Institute, November 3, 2017. Photo: OHSU/Kristyna Wentz-Graff

Stem cells continue to show great promise in some unconquerable conditions – but they also show some stubborn problems, like rejection. Complicating matters further is that preclinical research models have failed to provide answers to why the treatments can work high-profile medical miracles, but go so disastrously wrong in cases that appear identical.

But now, a team at Oregon Health and Science University says they have demonstrated a new research model in a very specific group of primates, they report in the journal Nature Communications.

“These results establish a new preclinical allogenic hematopoietic stem cell transplantation model for evaluation of (graft-vs.-host disease) prophylaxis and next-generation (stem cell) therapies for solid organ tolerance, cure of non-malignant hematological disease, and HIV reservoir clearance,” they write.

Thirteen monkeys from an exotic tropical place were the subjects of the latest experiments.

The cynomolgus macaques from Mauritius (also known as crab-eating monkeys) showed a better model than previously-used monkey species (like rhesus macaques) to find good donor matches. The benefits of the crab-eating monkeys is that they were geographically isolated and have highly limited immunogenetic diversity, which allowed for purer models, they write.

“Our studies have revealed conditions that generation rapid onset graft rejection… which can be exploited for subsequent studies,” they write. “Overall, this minor antigen alloreactivity mirrors the immune response in patients receiving hematopoietic stem cell transplantation grafts from major histocompatibility complex-matched unrelated and related donors and thus augurs well for the clinical relevance of this model.”

The OHSU team said in a statement that the breakthrough with the monkey models could shed light on one of the unexplained “cures” of the last decade: the phenomenon of “the Berlin patient.”

Timothy Ray Brown, an American, was diagnosed with HIV in 1995, and then developed leukemia about a decade later.

In 2007, Brown received a hematopoietic stem cell transplant for his cancer from a donor who had a rare genetic variant of a cell surface receptor that is HIV resistant.

Over the next three years, doctors determined that the virus had essentially been eradicated from his body.

Although assumed to have been the donated cells that wiped out the retrovirus from Brown’s body, new theories (and cases of the “cure”) have some scientists hypothesizing that it was instead the intense immune response triggered by the graft-vs.-host rejection battle that beat back the virus.

Advertisement
Advertisement