Das Madhurima, Chatterjee Sumanta, Basak Pratima, 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, Kolkata-700073, India.
J Stem Cells. 2009;4(4):229-41.
The bone marrow is the major site of haemopoiesis in adult human. It contains cells that represent the stages in the development of different types of blood cells e.g. myelocytes, metamyelocytes, erythroblasts, reticulocytes, and other lymphoid progenies etc. Bone marrow failure is primarily the result of a specific failure of bone marrow precursor cells to produce mature cells. N-ethyl N-nitroso urea (ENU) is one of the most potent mutagens that can create an abnormal bone marrow microenvironment by causing defect in haematopoietic stem cell maturation cascade. ENU is easy to administer in mouse, and some probable mutations can be helpful to create models of human diseased conditions like Myelodysplastic syndrome (MDS). MDS is considered as an intravascular bone marrow disorder, a combined structural-functional abnormality wherein the differentiation procedure of the bone marrow stem cell is either incomplete or defective. We assumed that Myelodysplastic syndrome stands in between an inhibitory cellular pattern and a positive overshoot of abnormal differentiations representing an unknown juncture where the mystery of aplasia and leukemia hide back. Instead of using a transgenic mouse model, we attempted to develop an experimentally induced murine model of preleukemia or human MDS like disease model. In doing so ENU has been administered i.p and the animals were examined on thirtieth day and peripheral blood haemogram was documented. Upon registering the appearance of abnormal peripheral blood scenario, the changes in the intravascular bone marrow (BM) architecture, cell surface receptor expression, e.g. Sca-1, c-Kit and the early and late phase apoptic patterns were noted. The results represented an interesting correlation in between bone marrow architecture, early stem cell receptor and apoptic marker expression resembling human MDS.
骨髓是成年人体内造血的主要部位。它包含代表不同类型血细胞发育阶段的细胞，例如髓细胞、晚幼粒细胞、成红细胞、网织红细胞以及其他淋巴系祖细胞等。骨髓衰竭主要是骨髓前体细胞无法产生成熟细胞的特定结果。N-乙基-N-亚硝基脲（ENU）是最有效的诱变剂之一，它可通过导致造血干细胞成熟级联缺陷来创建异常的骨髓微环境。ENU易于在小鼠中施用，一些可能的突变有助于创建人类疾病状况的模型，如骨髓增生异常综合征（MDS）。MDS被认为是一种血管内骨髓疾病，是一种结构 - 功能联合异常，其中骨髓干细胞的分化过程要么不完全要么有缺陷。我们假设骨髓增生异常综合征介于抑制性细胞模式和异常分化的阳性过度之间，代表着一个未知的节点，再生障碍和白血病的奥秘隐藏于此。我们没有使用转基因小鼠模型，而是试图开发一种实验诱导的白血病前期或类似人类MDS疾病模型的小鼠模型。在此过程中，通过腹腔注射施用ENU，并在第三十天对动物进行检查，记录外周血细胞计数。在记录到外周血出现异常情况后，观察血管内骨髓（BM）结构的变化、细胞表面受体表达，例如Sca-1、c-Kit以及早期和晚期凋亡模式。结果显示骨髓结构、早期干细胞受体和凋亡标志物表达之间存在有趣的相关性，类似于人类MDS。
