On February 22, the reporter of Science and Technology Daily learned from the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences that the research team of Wang Jinyong and the team of Zhang Mengyun, a professor of Guangzhou Medical University, cooperated to manipulate the combined expression of three important hematopoietic regulatory genes Runx1, Hoxa9 and Hoxa10 through stem cell gene editing for the first time, and successfully obtained artificial bone marrow seed cells with transplantation ability in mouse experiments, And after transplantation, it can achieve high chimerism in wild animals, long-term and multi-lineage hematopoiesis. The relevant results were recently published in the journal of the International Stem Cell Society, Stem Cell Report. Bone marrow transplantation, namely hematopoietic stem cell transplantation, is mainly used to treat multiple malignant blood tumors, Mediterranean anemia and other blood monogenetic diseases. However, the cell source of hematopoietic stem cell transplantation is mainly the bone marrow, peripheral blood or umbilical cord blood of blood or non-blood donors who have successfully matched. There are many restrictions on the source, limited quantity and high cost. Patients receiving allogeneic bone marrow transplantation often have immune rejection, which affects the quality of life. "Pluripotent stem cells, including natural human embryonic stem cells and induced pluripotent stem cells, are a kind of stem cells that can be cultured and expanded for a long time and can differentiate into all types of human cells." Wang Jinyong said that combining with gene editing technology, it can theoretically induce stem cell differentiation to obtain artificial bone marrow seed cells, thus enabling many patients to get rid of the dilemma of finding donor bone marrow. To measure the usefulness of artificial bone marrow, it is necessary to transplant it successfully in animals with complete immune system. The research team has constructed an embryonic stem cell line that can induce the expression of the combination of transcription factors Runx1, Hoxa9 and Hoxa10 through homologous recombination, and based on the two-step strategy of "regeneration of seed cells in vitro and maturation in vivo", transplanted the hematopoietic seed cells generated by differentiation in vitro into the pretreated wild-type mice. The results showed that the transplanted hematopoietic seed cells could produce complete mononuclear myeloid lineage, B-cell lineage and T-cell lineage in the peripheral blood, bone marrow, spleen and other tissues and organs of recipient mice for a long time. The results of single cell sequencing and clustering further showed that the regenerated myeloid cells, B cells and T cells in the peripheral blood of the recipient mice after transplantation had similar transcriptional spectrum characteristics with the cells from natural development. In order to analyze the cytological mechanism of long-term implantation of artificial bone marrow seed cells, the research team further detected myeloid progenitor cells and lymphoid progenitor cells derived from stem cells in the bone marrow of recipient mice. The second transplantation experiment confirmed that these regenerated progenitor cells have the ability to regenerate multiple blood lineage cells for a long time. "These artificial bone marrow seed cells have been successfully implanted in animals and kept stable for more than 6 months under the premise of the host immune system competition, which is equivalent to more than 20 years of human beings, and have differentiated and exported a variety of mononuclear, granulocyte and lymphocyte." Wang Jinyong said, moreover, no tumorigenic phenomenon was found in many batches of independent transplantation experiments, which preliminarily confirmed the safety of artificial bone marrow seed cells. The research results bring hope for the artificial bone marrow seed cells to replace the traditional source of bone marrow transplantation cells, and it is expected to establish the artificial bone marrow stem cell bank in the future to provide "spot" treatment for many patients
Edit：Ying Ying Responsible editor：Zhou Shu
Source：digitalpaper.stdaily.com
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