It has been established previously that up to 40% of mouse CD34+ hematopoietic stem cells are capable of internalizing exogenous dsDNA fragments both in vivo and ex vivo. Importantly, when mice are treated with a combination of cyclophosphamide and dsDNA, the repair of interstrand crosslinks in hematopoietic progenitors is attenuated, and their pluripotency is altered. Here we show for the first time that among various actively proliferating mammalian cell populations there are subpopulations capable of internalizing dsDNA fragments. In the context of cancer, such dsDNA-internalizing cell subpopulations display cancer stem cell-like phenotype. Furthermore, using Krebs-2 ascites cells as a model, we found that upon combined treatment with cyclophosphamide and dsDNA, engrafted material loses its tumor-initiating properties which we attribute to the elimination of tumor-initiating stem cell subpopulation or loss of its tumorigenic potential.
We studied the safety and efficiency of transplantation of autologous bone marrow cells in complex therapy of patients with spinal cord injury in the late period of the disease. In control group patients, meningomyeloradiculolis was performed, while in the main group surgical treatment was supplemented by transplantation of autologous bone marrow cells. Transplantation of BM stem cells into the cyst cavity and intravenously was well tolerated, did not cause allergic or inflammatory reactions in the early and delayed periods after surgery, and did not induce the formation of ossification foci in the nervous tissue. Analysis of the neurological status by ASIA, Bartel, and Ashworth scales showed that in the main group the positive clinical dynamics was more often observed than in the control. The decrease in neurological deficit included improvement of sensory and motor activity and conducting sensory function. Thus, transplantation of autologous bone marrow cells can be a novel safe strategy for the treatment of patients in the late period after spinal trauma.
We studied quantitative and functional parameters of bone marrow stem cells and mature lymphocyte population under conditions of impaired innervation in patients with injuries to the cervical and thoracic portions of the spinal cord. Our findings indicated the absence of deficiency of quantitative and proliferative potentials of stem cells and demonstrated intact subpopulation structure of mature lymphocytes and T-cell proliferative activity similar to that in donors. The content of CD34+ cells in patients did not differ from that in donors. The percentage of CD34+CD38- hemopoietic stem cells was elevated in patients, presumably due to increased proliferative activity of hemopoietic stem cells. The possibility of derivation and in vitro culturing of fibroblast-like cells with mesenchymal stem cell phenotype was demonstrated.
Poorly differentiated cell populations including tumor-initiating stem cells have been demonstrated to display a unique ability to natively internalize fragmented double-stranded DNA. Using this feature as a marker, we show that 0.1% to 6% of human glioblastoma cells from the bioptates can effectively internalize a fluorescently labeled DNA probe. Of these, using samples from 3 patients, 66% to 100% cells are also positive for CD133, a well-established surface marker of tumor-initiating glioma stem cells. Using the samples from primary malignant brain lesions (33 patients), we demonstrate that tumor grading significantly correlates (R = .71) with the percentage of DNA-internalizing cells. No such correlation is observed for relapse samples (18 patients).
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