15 February 2008

The immune system from embryonic stem cells

Embryonic stem cells are considered as a renewable source of primitive cells, theoretically capable of turning into cells of all organs and tissues. In addition to plasticity, these cells have another important characteristic – they express few histocompatibility antigens that cause rejection of transplanted tissues, which greatly facilitates the search for suitable donors.

In earlier works, an international group of researchers working under the leadership of Professor Nicholas Zavazava from the University of Iowa demonstrated the possibility of transformation of embryonic stem cells by introducing the HOXB4 gene into them, the protein of which directs the differentiation of non-specialized cells into hematopoietic cells and significantly enhances their proliferation. The introduction of such cells to mice with bone marrow devastated by radioactive radiation restored hematopoiesis, however, scientists did not analyze their ability to restore a normally functioning immune system, especially the ability to provide animals with protection from viruses and respond to vaccination. It was necessary to verify the ability of embryonic stem cells to restore the immune system lost during irradiation, since the embryos in the uterus do not need it.

In a new paper, the results of which are published in the journal Blood (Kun-Ming Chan et al., Hematopoiesis and immunity of HOXB4-induced embryonic stem cell-derived hematopoietic progenitor cells), the authors used HOXB4-containing embryonic stem cells to replace the bone marrow devastated by irradiation of transgenic mice that initially did not have a functional immune system. Transplantation of these cells ensured the restoration of stable hematopoiesis. Laboratory testing confirmed that the precursors of the blood cells formed in this case were transplanted embryonic stem cells.

After that, the authors infected the animals with LCMV, a common rodent virus, and observed changes in the activity of T cells, reflecting the effectiveness of the development of antiviral immunity. Despite the fact that the number of T cells forming was small, they reacted adequately to the virus entering the body. In addition, the appearance of B-lymphocytes and other immune cells necessary for the full functioning of the immune system was recorded in animals. In addition, vaccination of animals caused the formation of immune cells specific to the injected antigen. Compared with the control group, the experimental mice developed a less pronounced immune response to infection and vaccination, but it was registered and quite effective.

In addition, within 200 days after transplantation, none of the 70 animals had the formation of either malignant or benign tumors (the tendency of undifferentiated embryonic stem cells to malignancy is the main obstacle to their use in medicine).

The results obtained demonstrate for the first time the ability of embryonic stem cells expressing the HOXB4 protein to differentiate into full-fledged cells of the immune system. Experts believe that this work is a significant step in the development of cell therapy.

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