US and Chinese scientists said Thursday they have discovered an effective strategy that could prevent the human immune system from rejecting the grafts derived from human embryonic stem cells, a major problem now limiting the development of human stem cell therapies.

Using a novel "humanized" laboratory mice, the researchers found that one combination of two immune suppressing molecules worked perfectly to protect cells derived from human embryonic stem cells from immune rejection.

Human embryonic stem cells have the capacity to differentiate into a variety of cell types, but these foreign cells are often rejected by the human immune system because they are different from our own body's cells, or "allogenic."

One way to reduce the body's "allogenic immune response" is to suppress the immune system with immunosuppressant drugs.

But the long term use of toxic immunosuppressant drugs for patients pose serious health problems, including the increased risk of cancer and infection, said Xu Yang, a professor of biology at the University of California San Diego, who collaborated with scientists from China's Jilin University and Shenzhen Children's Hospital on the study.

Researchers had long been searching for a human immunity relevant model that would allow them to develop strategies to implant allogenic cells derived from embryonic stem cells safely.

"The problem is that we only had data from mouse immune system and those are not usually translatable in humans, because human and mouse immune systems are quite different," said Xu. "So what we decided to do was to optimize the humanized mouse that carries a functional human immune system."

To do that, they took immune deficient laboratory mice and grafted into their bodies human fetal thymus tissues and hematopoietic stem cells derived from fetal liver of the same human donor.

Ultimately, the mice contained a functional human immune system capable of mounting a vigorous immune rejection of foreign cells derived from human embryonic stem cells.

With these "humanized" mouse models, the researchers tested a variety of immune suppressing molecules alone or in combination.

They found that a combination of CTLA4-lg, an FDA-approved drug for treating rheumatoid arthritis, and a protein called PD-L1 allowed the allogeneic cells to survive in humanized mice without triggering an immune rejection.

"If we express both molecules in cells derived from human embryonic cells, we can protect these cells from the allogenic immune rejection," said Xu. "If you have only one such molecule expressed, there is absolutely no impact. We still don't know exactly how these pathways work together to suppress immune rejection, but now we've got an ideal system to study this."

Xu said they will next test the strategy on monkeys. He also believed the discovery and the development of their humanized mouse models may offer the much needed tools to develop ways to activate immune response to tumors, because these molecules are known to be important in allowing tumors to evade the human immune system.

The findings were published online in the US journal Cell Stem Cell.