Researchers at UT Southwestern find way to help donor adult blood stem cells overcome transplant rejection

Alec Zhang and Junke Zheng
Drs. Chengcheng ‘Alec’ Zhang (right) and Junke Zheng demonstrated in mice that adult blood stem cells can be regulated to head off transplant rejection.

The study, published Aug. 5 in Cell Stem Cell, showed for the first time that adult blood stem cells can be regulated to overcome an immune response that leads to transplant rejection. It also opens up further studies in stem cell immunology, said Dr. Chengcheng “Alec” Zhang, assistant professor of physiology and developmental biology at UT Southwestern and senior author of the study.

“We speculate that a common mechanism exists to regulate immune inhibitors in different types of stem cells,” he said.

Nearly 1 million people in the U.S. are living with or in remission from blood cancers; more than 135,000 are expected to be diagnosed this year. Blood and bone marrow stem cell transplants are needed when a patient’s body stops making enough healthy blood cells.

In this current study, UT researchers developed a culture “cocktail” that successfully supported adult blood stem cells from humans and from mice, and found that they express immune inhibitors on their surfaces that protect them from immune attack. Using the increased number of cultured blood stem cells, the scientists were able to overcome the protein barrier that alerts the immune system to foreign material and significantly repopulated healthy cells in the rodent transplantation recipients.

“We revealed that the expansion of adult blood stem cells through culture and an increase in cell surface expression of an immune molecule are the keys for this to happen,” Dr. Zhang said.

Other UT Southwestern researchers involved in the study were Dr. Junke Zheng, instructor of physiology and lead author; Dr. Masato Umikawa, a visiting instructor now an associate professor of cell biology at the University of the Ryukyus in Nishihara, Japan; Dr. Shichuan Zhang, postdoctoral researcher in radiation oncology; Dr. HoangDinh Huynh, postdoctoral researcher in physiology; Robert Silvany, senior research associate in physiology; and Dr. Benjamin P.C. Chen, assistant professor of radiation oncology. Dr. Lieping Chen, director of cancer immunology at the Yale Cancer Center and former professor of oncology and dermatology at the Institute for Cell Engineering in the Johns Hopkins University School of Medicine, also participated.


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