Chatterjee Sumanta, Basak Pratima, Das Madhurima, Das Prosun, Pereira Jacintha Archana, Dutta Ranjan Kumar, Chaklader Malay, Chaudhuri Samaresh, Law Sujata
Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, School of Tropical Medicine, C R Avenue, Kolkata-700073, India.
J Stem Cells. 2009;4(3):179-89.
The production of blood cells from bone marrow (BM) hematopoietic stem cells (HSC) is regulated by a number of cytokines and growth factors that influence cell survival; differentiation, proliferation and apoptosis in health and supposedly, such mechanisms are deregulated in diseased conditions. As far as cellular kinetics is concerned HSCs are relatively quiescent in adults, have the ability to replicate symmetrically and asymmetrically and predictably exhibit multi-lineage hematopoietic reconstitution potential. HSC drive hematopoiesis and homeostasis by contracting and expanding the pool of hematopoietic cells in the bone marrow. In mouse they can be identified immunophenotypically as Sca1+ c-kit cells. In aplastic anemia a drastic decline in the marrow efficacy to produce mature blood cells leads to bone marrow failure. In contrast, in leukemia hyper stimulated marrow leads to deregulated differentiation of immature hematopoietic stem cells with increased self-proliferation potential. In our experimental set up, we induced aplastic anemia by injecting busulfan and cyclophosphamide and leukemia by N-N' ethylnitrosourea intraperitoneally in inbred swiss albino mice. Indeed, HSCs and haematopoietic progenitor cells (HPCs) are vulnerable target for such disease oriented dysregulation which bears close correlation with the bone marrow microenvironmental damage. The present study aims at evaluating the possible mechanism(s) of deregulation in the bone marrow physiology with special reference to HSC surface receptor expression, cellular granularity, cell cycle status and overall marrow architecture. The investigations made so far revealed an interesting correlation between disease initiation and specific cytokinetic involvement of HSC in the BM microenvironment with particular reference to leukemia and aplastic anemia.
骨髓（BM）造血干细胞（HSC）产生血细胞的过程受到多种细胞因子和生长因子的调节，这些因子影响细胞存活、分化、增殖和凋亡，在健康状态下如此，在疾病状态下这些机制据推测会失调。就细胞动力学而言，造血干细胞在成体中相对静止，具有对称和不对称复制的能力，并且可预测地表现出多谱系造血重建潜能。造血干细胞通过收缩和扩大骨髓中造血细胞池来驱动造血和维持内环境稳定。在小鼠中，它们可通过免疫表型鉴定为Sca1+c-kit细胞。在再生障碍性贫血中，骨髓产生成熟血细胞的功效急剧下降导致骨髓衰竭。相反，在白血病中，过度刺激的骨髓导致未成熟造血干细胞分化失调，自我增殖潜能增加。在我们的实验设置中，我们通过向近交系瑞士白化小鼠腹腔注射白消安和环磷酰胺诱导再生障碍性贫血，通过注射N-亚硝基-N'-乙基脲诱导白血病。事实上，造血干细胞和造血祖细胞（HPC）是这种疾病导向性失调的易损靶点，这与骨髓微环境损伤密切相关。本研究旨在评估骨髓生理学失调的可能机制，特别关注造血干细胞表面受体表达、细胞颗粒度、细胞周期状态和整体骨髓结构。迄今为止的研究揭示了疾病起始与造血干细胞在骨髓微环境中特定细胞动力学参与之间的有趣关联，特别是关于白血病和再生障碍性贫血。
