SEOUL NATIONAL UNIVERSITY HOSPITAL

Professor Kim Hyo-Soo at the Seoul National University Hospital (SNUH) developed a screening method of long-term repopulating hematopoietic stem cells (LT-HSCs) which are young and excellently differentiated, and published the findings in Cell Stem Cell, a prominent journal in the field of stem cell research.

Developing an innovative source technology to make blood stem cells awake and put them to sleep

Facilitating commercialization by securing a large amount of long-term repopulating hematopoietic stem cells

Applicable to the development of medicine for leukemia and pernicious anemia as well as artificial blood

A research team led by Professor Kim Hyo-Soo of the Department of Internal Medicine at the Seoul National University Hospital (SNUH) (including Professors Hur Jin and Baek Sung Hee (School of Biological Sciences, SNU)) developed an innovative source technology that selectively sorts out long-term hematopoietic stem cells that produce diverse blood cells in the body securing a large amount in best conditions.

Bone marrow inside the bone acts as a niche for stem cells, especially blood stem and progenitor cells. The research team identified for the first time that KAI1/CD82 molecule is found only on long-term repopulating hematopoietic stem cells (LT-HSCs) out of blood stem and progenitor cells which are forebears of blood cells in the bone marrow. Furthermore, they discovered that the KAI1 molecule interacts with DARC/CD234 protein of the macrophage, a type of immune cells, to activate the TGF-beta1/Smad3 axis, maintaining LT-HSCs in dormant status.

The academic community found a way to wake up dormant blood stem cells in the bone marrow and amplify their number, but the blood stem cells amplified in this way tend to lose the ability to generate blood cells in the long term. In other words, the awaken blood stem cells have a weak blood-forming ability even after being applied to patients. To overcome this issue, it is needed to understand how to secure a great number of amplified cells and put them to sleep to be stored. This study suggests a solution to this challenging problem. A core technology was discovered to put the amplified blood stem cells to sleep while maintaining their functions and youth and then store them by treating DARC protein, which is either expressed by macrophages or culturing with DARC expressing macrophages.

This new technology can be utilized to develop a medicine for bone marrow failure syndromes such as leukemia and pernicious anemia or to increase the success rates of bone marrow transplant. If the method of amplifying and storing LT-HSCs is commercialized, it would be possible to create a blood stem cell bank that can quickly provide LT-HSCs to patients in urgent need. Moreover, it will serve as the foundation for forming immune cells and artificial blood.

Professor Kim Hyo-Soo said, "Since we have developed a source technology of controlling hematopoietic stem cells applicable to both mice and humans, the development of medicine for leukemia and pernicious anemia as well as the clinical application of optimized bone marrow transplant will be facilitated." He asserted his plan to conduct a clinical study and commercialize the source technology in five years. He also emphasized the government's continuous support as the ground for achieving such a great performance. "The generous support of the Ministry of Health and Welfare allowed us to hire Professor Hur Jin, who made this long-term challenge bear fruit."

This study was carried out for five years based on [1] the Innovative Research Institute for Cell Therapy (A062260) and Korea Health Technology R&D Project (HI14C1277) through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, [2] the Bio and Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIP) (NRF-2015M3A9B4051041), (NRF-2015M3A9B4051198) [3] the Creative Research Initiatives Program (2009-0081563) of the NRF. Findings were published in the Cell Stem Cell (5-year IF=24.565), a world-class journal in the field of stem cell research, on March 18, 2016.