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流式细胞术分析和扫描电镜比较研究再生障碍性贫血小鼠模型中原始 Sca-1 阳性骨髓造血干细胞。

Primitive Sca-1 Positive Bone Marrow HSC in Mouse Model of Aplastic Anemia: A Comparative Study through Flowcytometric Analysis and Scanning Electron Microscopy.

机构信息

Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, 108, C.R. Avenue, Kolkata-700073, India.

出版信息

Stem Cells Int. 2010;2010:614395. doi: 10.4061/2010/614395. Epub 2009 Oct 28.

Abstract

Self-renewing Hematopoietic Stem Cells (HSCs) are responsible for reconstitution of all blood cell lineages. Sca-1 is the "stem cell antigen" marker used to identify the primitive murine HSC population, the expression of which decreases upon differentiation to other mature cell types. Sca-1(+) HSCs maintain the bone marrow stem cell pool throughout the life. Aplastic anemia is a disease considered to involve primary stem cell deficiency and is characterized by severe pancytopenia and a decline in healthy blood cell generation system. Studies conducted in our laboratory revealed that the primitive Sca-1(+) BM-HSCs (bone marrow hematopoietic stem cell) are significantly affected in experimental Aplastic animals pretreated with chemotherapeutic drugs (Busulfan and Cyclophosphamide) and there is increased Caspase-3 activity with consecutive high Annexin-V positivity leading to premature apoptosis in the bone marrow hematopoietic stem cell population in Aplastic condition. The Sca-1(bright), that is, "more primitive" BM-HSC population was more affected than the "less primitive" BM-HSC Sca-1(dim ) population. The decreased cell population and the receptor expression were directly associated with an empty and deranged marrow microenvironment, which is evident from scanning electron microscopy (SEM). The above experimental evidences hint toward the manipulation of receptor expression for the benefit of cytotherapy by primitive stem cell population in Aplastic anemia cases.

摘要

自我更新的造血干细胞 (HSCs) 负责重建所有血细胞谱系。Sca-1 是用于鉴定原始鼠 HSC 群体的“干细胞抗原”标志物,其表达在分化为其他成熟细胞类型时会降低。Sca-1(+) HSCs 维持骨髓干细胞池在整个生命周期中。再生障碍性贫血是一种被认为涉及原发性干细胞缺乏的疾病,其特征是严重的全血细胞减少症和健康血细胞生成系统的衰退。我们实验室进行的研究表明,在接受化疗药物(白消安和环磷酰胺)预处理的实验性再生障碍性动物中,原始 Sca-1(+) BM-HSCs(骨髓造血干细胞)受到显著影响,并且 Caspase-3 活性增加,随后 Annexin-V 阳性率升高,导致骨髓造血干细胞群体在再生障碍性条件下过早凋亡。Sca-1(bright),即“更原始”的 BM-HSC 群体比“较不原始”的 BM-HSC Sca-1(dim)群体受到的影响更大。细胞群体和受体表达的减少与空骨髓微环境直接相关,这从扫描电子显微镜 (SEM) 中可以明显看出。上述实验证据表明,在再生障碍性贫血病例中,通过原始干细胞群体对受体表达进行操纵以有利于细胞治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6225/2963143/6bb91a17fd11/SCI2010-614395.001.jpg

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