CAJ | 학술논문

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。
배경：진성홍세포증다증환자골수적고증식저조망특성사기조혈간세포식입NOD/SCID소서후성공분화출립홍계세포，단기능부식입병개선재생장애성빈혈소서조혈공능，목전국내외상미유보도。목적：탐토JAK2양성진성홍세포증다증환자골수단개핵세포식입후대재생장애성빈혈소서조혈중건적영향。방법：응용주사용중조인γ-간우소연합백소안적방법건립재생장애성빈혈소서모형，수궤분위실험조(n=10)화대조조(n=10)，급약결속후제5천실험조경미정맥수주진성홍세포증다증환자골수단개핵세포현액，대조조동법수주등용적생리염수。수주후제14천검측소서외주혈상규、골수세포형태、골수조직병리변화이급소서외주혈화골수내CD45+세포적백분함량。결과여결론：수주후제14천，실험조소서혈세포계수삼계감소，골수도편가견산재림파세포화조기조혈세포，골수조직활검가견골수증생감저，소량립계세포급유홍세포，미견거핵세포，여대조조비교，조혈공능무명현개선。대조조소서외주혈급골수균미검측도CD45+세포，실험조소서외주혈급골수균가검측도인원화적CD45+세포，차골수중CD45+세포비외주혈고，제시JAK2V617F양성진성홍세포증다증환자골수단개핵세포능성공식입재생장애성빈혈소서체내，단혈상규、골수도편급활검결과현시미능명현개선골수조혈공능。
BACKGROUND:As the high proliferation and low apoptosis of the bone marrow in polycythemia vera patients, hematopoietic stem cels transplanted into NOD/SCID mice can differentiate into erythroid cels, but whether hematopoietic stem cels transplantation could improve the hematopoietic function of aplastic anemia mice is not yet reported. OBJECTIVE:To investigate whether transplantation of bone marrow mononuclear cels 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-γplus busulfan, and then, these mouse models were randomly divided into experimental group (n=10) and control group (n=10). Bone marrow mononuclear cels 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 cels, bone marrow biopsy, and percentage of CD45+ cels 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 smal amount of granulocyte cels 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+ cels 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+ cels was measured in the bone marrow than in the peripheral blood of experimental group mice. Experimental findings indicate that bone marrow mononuclear cels from polycythemia vera patients with positive JAK2V617F mutation can be engrafted into aplastic anemia mice, but cannot improve the hematopoietic function of mice.