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慢性粒细胞白血病患者骨髓间充质干细胞的生物学特性及其造血调控 被引量:2

Biological characteristics and regulatory effects of bone marrow mesenchymal stem cells on hematopoietic stem cells in patients with chronic myelocytic leukemia
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摘要 背景:由于慢性粒细胞白血病存在造血微环境异常和免疫异常,推测间充质干细胞可能在慢性粒细胞白血病的病理过程中扮演了一个重要角色。目的:观察慢性粒细胞白血病骨髓间充质干细胞的生物学特征和对造血调控的影响,比较其与正常人骨髓来源的间充质干细胞的异常。方法:分离正常人和慢性粒细胞白血病患者的骨髓间充质干细胞,分别检测它们的形态、表型、生长曲线和对T细胞活化的能力;将它们分别与脐带血干细胞共培养,检测共培养体系中对集落形成的影响和相关分子表达的差异。结果与结论:慢性粒细胞白血病患者和正常志愿者骨髓来源的间充质干细胞的细胞形态、表型和干细胞的倍增时间均没有差异,慢性粒细胞白血病患者的骨髓间充质干细胞抑制T细胞活化的能力减弱;共培养体系中,悬浮细胞簇增加,说明造血干细胞与间充质干细胞之间的黏附性减弱,同时蛋白和RNA水平显示慢粒组中基质金属蛋白酶9升高,同时使ICAM-1的KitL从膜形式转变为可溶性形式。结果提示,慢性粒细胞白血病骨髓间充质干细胞是细胞分化发育的微环境,其基础的机制在于基质金属蛋白酶9对细胞外基质的降解和黏附分子的裂解,改变骨髓微环境对造血干细胞黏附,增殖和分化的支持作用,导致造血干细胞异常增殖和动员,降低了恶变细胞对免疫细胞的敏感性导致免疫逃逸。 BACKGROUND:Chronic myelocytic leukemia had abnormal hematopoietic microenvironment and abnormal immunology.We presumed that mesenchymal stem cells(MSCs) may play an important role in pathological process of chronic myelocytic leukemia.OBJECTIVE:To investigate biological characteristics of chronic myeloid leukemia hemangioblasts and its regulatory effects,and to compare the differences with bone marrow mesenchymal stem cells(BMSCs) from normal donors.METHODS:MSCs were isolated from normal donors and BMSCs from patients with chronic myelocytic leukemia.The differences in morphology,phenotype,cell growth and T lymphocyte activation were examined.Obtained cells were cocultured with umbilical cord blood stem cells.The effects on colony formation and differences in relative molecule expression were determined in coculture system.RESULTS AND CONCLUSION:There were no differences in morphology,phenotype and doubling time of MSCs from patients and normal donors.Inhibitory ability of BMSCs on T cell activation was weakened in chronic myelocytic leukemia patients.In coculture system,suspended cells became more,which indicated that the adherence between hematopoietic stem cells and MSCs was weakened.Simultaneously,protein and RNA levels revealed that matrix metalloproteinase-9 levels increased,and KitL of intercellular adhesion molecule-1 changed from membrane form into soluble form.The results showed that BMSCs of chronic myelocytic leukemia patients were the microenvironment of cell differentiation and development.Its basic mechanisms were the degradation of matrix metalloproteinase-9 on extracellular matrix and split of adhesion molecule.Changes in bone marrow microenvironment support effects on adhesion,proliferation and differentiation of hematopoietic stem cells lead to abnormal proliferation and mobilization of hematopoietic stem cells,decrease sensitivity of cancer cells on immunocytes,resulting in immune escape.
出处 《中国组织工程研究与临床康复》 CAS CSCD 北大核心 2010年第45期8377-8381,共5页 Journal of Clinical Rehabilitative Tissue Engineering Research
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