Blocking The Differentiation Of Mesenchymal Stem Cell To Neural Cell And Its Correlation With Tumorigenesis

Bone mesenchymal stem cells (BMSCs) are the non-hematopoietic stem cells presented in the bone marrow, which possesses the capacity for self-renewal, proliferation and the potential of multi-directional differentiation that could differentiate into osteoblast, chondroblast, myoblast, adipocyte, neuron and cardiomyocyte. Cancer stem cell (CSC) is a minority population within a tumor that possesses the capacity of self-renew, proliferation and causing the heterogeneous lineages of cancer cells that comprise the tumor. Although there are substantial evidences for the existence of CSCs in leukemia, breast cancer and brain tumor, CSCs are distinct from the cell of origin. With in-depth study on CSC, the correlation of BMSCs with origin of CSC has become a major concern.This article we investigated the relationship of CSC and stem cells based on the perspective of cell proliferation and differentiation. Rat BMSCs were used to establish a neural cell differentiation model. We observed the changes of in cell at different time points after arrested the normal differentiation process, and explored the correlation of stem cells with tumorigenesis.The specific methods as follows:1. BMSCs were separated from rat bone marrow by plastic adherence methods and cultured in vitro on appropriate conditions.2. Establish the neural cell differentiation model:BMSCs were treated with neuronal induction medium, which containing P-mercaptoethanol (BME). The expression of neuron-specific enolase (NSE), neurofilament protein (NF) and glial fibrillary acidic protein (GFAP) were measured by immunohistochemical.3. Establish the differentiation interrupted model, explored the correlation of stem cells with tumorigenesis:BMSCs are divided into differentiated group and interrupted groups. Differentiated group cells are subjected to the neuronal differentiation protocol, while simultaneously the normal differentiation processes were arrested at different time points in interrupted group. Morphological observation, immunohistochemistry, karyotype analysis and other means were used to detect the interrupted cells. Through the study on compare the difference between BMSCs, normal differentiation cells and different-timepoint-arrest-differentiation cells, and explore the correlation of stem cells with tumorigenesis.The results are as follows:1. BMSCs were isolated from rat marrow and culture successfully in vitro.2. BMSCs were induced to differentiate into neurons. After induced treatment, the cells exhibited neuronal characteristics. The neuron-like cells were positivity for both NSE and NF, but negative for GFAP.3. The exploration regarding interruption of differentiation of BMSCs shows that after arresting the differentiation cells were emerged malignant characteristics. Different time points for interrupting differentiation lead to different nerve cells specific protein expression quantity and malignant degree. The degree of differentiation of the resultant cancer will be determined by the stage in the process of determination at which the malignant event occurs or is manifested, the earlier interrupt on stem cell leads to the lower differentiation malignant cell with faster proliferation and higher degree of malignancy, vice versa.In conclusion, interrupting stem cells differentiation caused the cells staying the intermediate stage of differentiation and unlimited proliferated, which might make the conversion of stem cells to CSC. Our research provided a new experimental data for hypothesis that CSC originated from normal stem cells.