真性红细胞增多症患者骨髓单个核细胞植入再生障碍性贫血小鼠

背景：真性红细胞增多症患者骨髓的高增殖低凋亡特性使其造血干细胞植入NOD/SCID小鼠后成功分化出粒红系细胞，但其能否植入并改善再生障碍性贫血小鼠造血功能，目前国内外尚未有报道。 目的：探讨JAK2阳性真性红细胞增多症患者骨髓单个核细胞植入后对再生障碍性贫血小鼠造血重建的影响。 方法：应用注射用重组人γ-干扰素联合白消安的方法建立再生障碍性贫血小鼠模型，随机分为实验组(n=10)和对照组(n=10)，给药结束后第5天实验组经尾静脉输注真性红细胞增多症患者骨髓单个核细胞悬液，对照组同法输注等容积生理盐水。输注后第14天检测小鼠外周血常规、骨髓细胞形态、骨髓组织病理变化以及小鼠外周血和骨髓内CD45+细胞的百分含量。 结果与结论：输注后第14天，实验组小鼠血细胞计数三系减少，骨髓涂片可见散在淋巴细胞和早期造血细胞，骨髓组织活检可见骨髓增生减低，少量粒系细胞及幼红细胞，未见巨核细胞，与对照组比较，造血功能无明显改善。对照组小鼠外周血及骨髓均未检测到CD45+细胞，实验组小鼠外周血及骨髓均可检测到人源化的CD45+细胞，且骨髓中CD45+细胞比外周血高，提示JAK2V617F阳性真性红细胞增多症患者骨髓单个核细胞能成功植入再生障碍性贫血小鼠体内，但血常规、骨髓涂片及活检结果显示未能明显改善骨髓造血功能。  中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Transplantation of bone marrow mononuclear cells from polycythemia vera patients into aplastic anemia mice

BACKGROUND:As the high proliferation and low apoptosis of the bone marrow in polycythemia vera patients, hematopoietic stem cells transplanted into NOD/SCID mice can differentiate into erythroid cells, but whether hematopoietic stem cells transplantation could improve the hematopoietic function of aplastic anemia mice is not yet reported. OBJECTIVE:To investigate whether transplantation of bone marrow mononuclear cells with JAK2V617F mutation from polycythemia vera patients can influence hematopoietic reconstruction in aplastic anemia mice. METHODS:Severe aplastic anemia mouse models were established by using recombinant human interferon-γ plus busulfan, and then, these mouse models were randomly divided into experimental group (n=10) and control group (n=10). Bone marrow mononuclear cells isolated from polycythemia vera patients with positive JAK2V617F mutation were transplanted into the mice in the experimental group via tail vein at 5 days after drug withdrawal.  The same volume of normal saline was administered to the control group. Routine peripheral blood test, morphology of bone marrow cells, bone marrow biopsy, and percentage of CD45+ cells in the peripheral blood and marrow were determined at 14 days after transplantation. RESULTS AND CONCLUSION:At 14 days after transplantation, pancytopenia occurred in the experimental group, bone marrow smears showed scattered lymphocytes and hematopoietic progenitors, and bone marrow biopsy presented that hematopoietic tissues were reduced and a small amount of granulocyte cells and erythroblasts could be seen, but megakaryocytes were rare. In contrast to the control group, there was no improvement in the hematopoietic function of mice in the experimental group. CD45+ cells were detectable in the peripheral blood and bone marrow in the experimental group, but not in the control group; and a higher percentage of CD45+ cells was measured in the bone marrow than in the peripheral blood of experimental group mice. Experimental findings indicate that bone marrow mononuclear cells from polycythemia vera patients with positive JAK2V617F mutation can be engrafted into aplastic anemia mice, but cannot improve the hematopoietic function of mice.