Background Overwhelming evidences on chronic myeloid leukemia （CML） indicate that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell （HSC） origin of C...Background Overwhelming evidences on chronic myeloid leukemia （CML） indicate that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell （HSC） origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated. Methods We have previously isolated fetal liver kinase-l-positive （Flkl＋） cells carrying the BCR/ABL fusion gene from the bone marrow of Ph＋ patients with hemangioblast property. In this study, we isolated CML patient-derived FIk1＋CD31-CD34- mesenchymal stem cells （MSCs） and detected their biological characteristics and immunological regulation using fluorescence in situ hybridization （FISH） analysis, fluorescence activated cell sorting （FACS）, enzyme-linked immunoadsorbent assay, mixed lymphocyte reaction assays; then we compared these characters with those of the healthy donors. Results CML patient-derived FIk1＋CD31-CD34- MSCs had normal morphology, phenotype and karyotype while appeared impaired in immuno-modulatory function. The capacity of patient FIk1＋CD31-CD34- MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. Conclusions CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than hematopoietic stem cells （HSCs）. MSCs might be a potential target for developing efficacious treatment for CML.展开更多
目的观察术中富集骨髓千细胞构建的组织工程骨在山羊脊柱横突间融合的成骨效果，为组织工程骨探索一种新型的构建方法。方法将多聚左旋赖氨酸（poly—L—lysine，PLL）修饰于山羊脱钙骨基质（demineralized bone matrix，DBM）制备成基...目的观察术中富集骨髓千细胞构建的组织工程骨在山羊脊柱横突间融合的成骨效果，为组织工程骨探索一种新型的构建方法。方法将多聚左旋赖氨酸（poly—L—lysine，PLL）修饰于山羊脱钙骨基质（demineralized bone matrix，DBM）制备成基质材料（PLL—DBM）；以山羊横突间隙为植骨模型，观察PLL-DBM富集骨髓细胞构建的组织工程骨（ⅠA组）的成骨能力；对照组为自体髂骨组（ⅠB组）、DBM富集骨髓组（ⅡC组）、空白DBM组（ⅡD组）。于术后第16周取融合段标本行X线片、三维CT及CT值检测和生物力学检测，对比分析、评价其成骨能力。结果X线表现：ⅠA组、ⅠB组融合范围基本相同，明显较ⅡC组宽，ⅡD组基本无融合。三维CT：ⅠA组的CT值为（696．76±102．75）HU，ⅠB组的CT值为（766．03±69．24）HU，二者差异无统计学意义（P〉0．05），均明显较ⅡC组高（P〈0．05），ⅡC组CT值较ⅡD组高（P〈0．01）。生物力学性能：ⅠA、ⅠB两组最大载荷、抗弯强度比较差异均无统计学意义（P〉0．05），ⅠA组较ⅡC组高（P〈0．01，0．05），ⅠB组较ⅡC组高（P〈0．01），ⅡC组较ⅡD组高（P〈0．01）。结论PLL—DBM术中富集骨髓干细胞快速构建的组织工程骨是一种理想的组织工程骨，其成骨能力与自体髂骨相当。展开更多
文摘Background Overwhelming evidences on chronic myeloid leukemia （CML） indicate that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell （HSC） origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated. Methods We have previously isolated fetal liver kinase-l-positive （Flkl＋） cells carrying the BCR/ABL fusion gene from the bone marrow of Ph＋ patients with hemangioblast property. In this study, we isolated CML patient-derived FIk1＋CD31-CD34- mesenchymal stem cells （MSCs） and detected their biological characteristics and immunological regulation using fluorescence in situ hybridization （FISH） analysis, fluorescence activated cell sorting （FACS）, enzyme-linked immunoadsorbent assay, mixed lymphocyte reaction assays; then we compared these characters with those of the healthy donors. Results CML patient-derived FIk1＋CD31-CD34- MSCs had normal morphology, phenotype and karyotype while appeared impaired in immuno-modulatory function. The capacity of patient FIk1＋CD31-CD34- MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. Conclusions CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than hematopoietic stem cells （HSCs）. MSCs might be a potential target for developing efficacious treatment for CML.
文摘目的观察术中富集骨髓千细胞构建的组织工程骨在山羊脊柱横突间融合的成骨效果，为组织工程骨探索一种新型的构建方法。方法将多聚左旋赖氨酸（poly—L—lysine，PLL）修饰于山羊脱钙骨基质（demineralized bone matrix，DBM）制备成基质材料（PLL—DBM）；以山羊横突间隙为植骨模型，观察PLL-DBM富集骨髓细胞构建的组织工程骨（ⅠA组）的成骨能力；对照组为自体髂骨组（ⅠB组）、DBM富集骨髓组（ⅡC组）、空白DBM组（ⅡD组）。于术后第16周取融合段标本行X线片、三维CT及CT值检测和生物力学检测，对比分析、评价其成骨能力。结果X线表现：ⅠA组、ⅠB组融合范围基本相同，明显较ⅡC组宽，ⅡD组基本无融合。三维CT：ⅠA组的CT值为（696．76±102．75）HU，ⅠB组的CT值为（766．03±69．24）HU，二者差异无统计学意义（P〉0．05），均明显较ⅡC组高（P〈0．05），ⅡC组CT值较ⅡD组高（P〈0．01）。生物力学性能：ⅠA、ⅠB两组最大载荷、抗弯强度比较差异均无统计学意义（P〉0．05），ⅠA组较ⅡC组高（P〈0．01，0．05），ⅠB组较ⅡC组高（P〈0．01），ⅡC组较ⅡD组高（P〈0．01）。结论PLL—DBM术中富集骨髓干细胞快速构建的组织工程骨是一种理想的组织工程骨，其成骨能力与自体髂骨相当。
