Thursday , January 20 2022

Hematologic tumor patients found clues to prevent transplant complications’


[그림=서울대병원 신동엽 연구팀은 생리적 저산소환경에서 체외 조혈모세포의 T림프구 전구세포와 T세포 증폭 생산 가능성을 확인했다.]

A domestic medical team has found a way to resolve the complications that may occur during hematopoietic stem cell transplantation.

Shin Dong-yeop’s research team in the Department of Hematology and Oncology at Seoul National University Hospital published these findings on the 4th.

The research team confirmed that it can effectively produce ‘lymphocyte progenitor cells’ from hematopoietic stem cells in vitro. When a hematopoietic stem cell transplant is performed by a hematopoietic stem cell transplant, a T-lymphocyte progenitor cell is transplanted simultaneously to reduce fatal infections that may occur after transplantation.

The research team stated, “The results of this study are expected to have a major impact on the future development of T cell therapy and patients receiving hematopoietic stem cell transplant.”

Hematopoietic stem cell transplantation is a treatment for transplantation of healthy hematopoietic stem cells after cancer cells and hematopoietic stem cells have been removed from hematopoietic patients. It is a very effective and important treatment for the cure of various types of blood cancer such as aplastic anemia, myelodysplastic syndrome such as myelodysplastic syndrome, refractory / refractory leukemia, lymphoma, and multiple myeloma.

However, this method carries a very high risk of complications and can only be treated in a selected patient group. In particular, immune impairment due to inadequate development of the T lymphocyte system causes fatal complications such as cytomegalovirus infection, leading to death.

T lymphocytes, commonly referred to as T cells, are involved in cellular immunity, attack and destroy cancer cells, and play an important role in the prevention of various viral infections. If these T cells are not working properly, the immune system is destroyed. T lymphocytes differentiate from hematopoietic stem cells and develop from the thymus through T lymphocyte progenitor cells.

The development process of T lymphocytes differs from that of other immune cells, so it has been difficult to produce effectively with conventional methods. Although the method by co-culture with mouse-derived thymocytes has been partially successful, it is a technique that cannot be applied to patients. The research team first focused on the development of technology for the application of patients, excluding mouse-derived cells and proteins, and conducted the experiment.

To establish the conditions for the production of T lymphocyte progenitor cells, the research team extracted umbilical cord blood hematopoietic stem cells with high purity, and then created a thymus mimic environment using recombinant proteins and human-derived cytokines.

Mixing cell culture conditions in a physiologically hypoxic environment under these heterogeneous cell culture culture conditions resulted in enhanced amplification and production of T lymphocyte progenitor cells. It has been confirmed that this phenomenon is further doubled by ascorbic acid (vitamin C), a representative antioxidant.

The research team verified these findings through a three-dimensional culture of organoids (artificial thymus) for one month. It was confirmed by intracellular cytokine production experiment that T lymphocyte progenitor cells produced in vitro under conditions of physiological hypoxic environment and ascorbic acid develop into T lymphocytes that act as true immune cells. That is, the possibility of swelling of T lymphocyte progenitor cell and T cell production in vitro was confirmed by hematopoietic stem cells.

Professor Shin Dong-yeop said, “Having tested various substances and culture conditions more than 200 times to reduce fatal infections caused by T lymphocyte deficiency after hematopoietic stem cell transplantation, we found such an approach . ” It is expected to contribute to improving treatment outcomes for patients undergoing blast transplantation and upgrading the rapidly developing cell therapy technology in recent years. “

The results of this study were published in the recent issue of’Stem Cells’, a journal in the field of stem cells.

Moon Se-young Correspondent [email protected]

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