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Recent studies regard bone marrow stromal cells as a potential candidate for cellular therapy of traumatic brain injury and thus as an attractive alternative for embryonic and fetal stem cells. Numerous experiments indicate that bone marrow stromal cells play an important role in the repair of injured brain tissue and also support healing processes. Findings of in vitro and in vivo studies show that these cells have an ability to differentiate into cells of multiple tissues, including neurons and glial cells and to secrete an array of growth factors and cytokines, which have an influence on repair of damaged tissue. In addition, treatment of traumatic brain injury with bone marrow stromal cells promotes functional recovery of injured animals. Taking this into consideration, there is hope for using bone marrow stromal cells in brain injury therapy, which is very difficult because of specific events that occur in the pathological conditions. However, mechanisms responsible for the observed therapeutic potential of bone marrow stromal cells still remain unclear. The review presents achievements in studies on bone marrow stromal cells as a source of therapeutic benefits in treatment of traumatic brain injury and addresses the question of their possible future use in clinical trials.
Experimental studies have shown that bone marrow stromal cells (BMSCs) promote functional recovery after traumatic brain injury. The beneficial effects of BMSCs therapy were demonstrated after intravenous, intraarterial and intracerebral transplantation of these cells. A reasonable explanation for the benefit provided by BMSCs is that these cells stimulate regenerative changes in the damaged brain, including glial remodeling. The aim of the present study was to determine and compare the time course of the astrocyte and microglial/ macrophage cell reaction to cerebral cortex injury after intracerebral and intravenous administration of BMSCs. Female Wistar rats were subjected to cerebral cortex injury followed by the injection of BMSCs or PBS directly to the injury site or to the tail vein. Using histology and immunohistochemistry, the distribution of astrocytes and microglia/macrophages was analyzed in the injured cerebral cortex. BMSCs treatment affected glial cell response to brain injury. The effects of BMSCs activity were dependent on the site of their administration. Intracerebral transplantation of BMSCs showed significant effect on the astrocyte response whereas intravenous route of BMSCs administration increased especially the microglia/ macrophages number in the injured brain. The results suggest that implanted cells can enhance the restorative processes in the injured brain through the stimulation and modulation of the cellular response to injury.
The present study was undertaken to determine a possible influence of fludarabine (fludarabine phosphate, F-ara-AMP) on the cell viability and count. The experiments were performed in vitro on human acute lymphoblastic MOLT-4 cells, human acute myeloblasts ML-1 cells, and human histiocytic lymphoma U-937 cells. The research was conducted using the spectrophotometric and Beckman Coulter methods. The cell viability was analyzed using MTT assay. The cell count was detected using an electronic Z2 Coulter counter. Temporary changes in the cell viability and count were assessed at 24h and 48h after F-ara-AMP application. The in vitro activity of fludarabine phosphate against MOLT-4, ML-1, and U-937 cells was compared. F-ara-AMP applied at the four concentrations - 250 nM, 500 nM, 750 nM, and 1 цМ - distinctly decreased the viability and count of the pathological hematopoietic cells. The effects of F-ara-AMP on MOLT-4, ML-1, and U-937 cells were dependent on the tested agent and its dose, the time intervals after the agent application, and the cell line used. ML-1 and U-937 cells appeared to be more resistant than MOLT-4 cells to the action of fludarabine phosphate. The in vitro response of the three human pathological hematopoietic cell lines to the F-ara-AMP action, was shown.
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