The bone marrow stem stromal imbalance - a key feature of disease progression in case of myelodysplastic mouse model

Myelodysplastic syndromes (MDSs) represent a spectrum of disorders that are generally thought to arise from a defective hematopoietic stem cell leading to clonal, dysregulated hematopoiesis. Although it is generally agreed that the marrow microenvironment plays a role in the biology of MDS, it is unclear whether this represents an intrinsically abnormal stromal compartment derived from the MDS clone. Hematopoiesis requires cooperation between progenitors and a variety of functionally and phenotypically different cell types that form the bone marrow stroma. Stromal abnormalities suspected to contribute to the pathology of bone marrow disorder with impaired hematopoiesis. Several studies on human MDS bone marrow microenvironment revealed functional alteration and increased cellular apoptosis thus contribute to the pathology of the disease progression.In this present study, we have investigsated alterations in the hematopoietic microenvironment and underlying mechanisms involved in the disease progression of MDS animal model. We presented the results of bone marrow single cell culture study, Long term bone marrow adherent culture study (LTBMC) and their functional efficacy,flowcytometric characterization of stem (Sca1+c-kit+) and stromal (Sca1+CD44+)progenitor cell population and expression level of extracellular apoptosis marker(Annexin v) in the bone marrow cells of MDS animal model. Bone marrow single cellculture study of MDS animal showed impairment in the normal cellular generation,proliferation and presence of apoptic cells. Long term liquid Bone marrow stromal cellcolony formation assay from MDS bone marrow cells showed significant difference inthe colony formation and their maintenance than the control groups of animals. Immunefunctional capacity of the bone marrow stromal cells through cell mediated immune(CMI) parameter study denoted defects in the stromal microenvironment. Decreasedexpression of bone marrow long-term primitive hematopoietic population and stromalprogenitor population depicted bone marrow abnormality in case of MDS animal model,which bears significant correlation with high expression level of apoptosis marker in thebone marrow cells.From the above experimental study we tried to highlight the abnormal bone marrowmicroenvironment and alteration in the bone marrow cell surface marker expression,which could be the probable mechanism of evolution and disease progression in case ofMDS animal model.