Candidates For Cell Replacement Therapy Research Articles

Green fluorescent protein‐labeled mapping of neural stem cells migrating towards damaged areas in the adult central nervous system

Neural stem cells, which are clonogenic cells with multilineage differentiation properties from regions of the fetal brain, cortex and hippocampus, are currently considered as powerful candidates for cell replacement therapy in neurodegenerative disorders, such as Parkinson's disease. A key issue is whether stem cells can survive, migrate and differentiate following transplantation into the adult CNS. Here, enhanced green fluorescent protein plasmid electroporation-transfected neural stem cells from the fetal cortex were grafted into the striatum of a rat model of Parkinson's disease. We found most of the grafted cells could survive in the adult parkinsonian rat brain and migrated towards damaged areas, while they moved randomly in the normal brain. Several grafted cells differentiated into neurons.

Analysis of neural stem cells by flow cytometry: cellular differentiation modifies patterns of MHC expression

Neural stem cells are currently considered very hopeful candidates for cell replacement therapy in neurodegenerative pathologies such as Parkinson’s disease. Here we show that different cell types derived from neurospheres amplified in vitro can be identified by FACS analysis relying solely on physical parameters (FSC/SSC) or autofluorescence. Additionally, after treatment with a panel of inflammatory cytokines, neurospheres and their differentiated progeny were shown to express MHC antigens which could potentially cause transplant rejection. Astrocytes expressed the highest levels of MHC. Hence removing such cells prior to transplantation could potentially optimise transplant survival.

Regulation of MHC class II expression in the central nervous system

Cell replacement therapy (CRT) is one of the most effective approaches used to alleviate symptoms of neurodegenerative syndromes such as cerebellar ataxia (CA). Human olfactory epithelium mesenchymal stem cells (OE-MSCs) have been recognized as a promising candidate for CRT, due to their distinctive features including immunomodulatory properties and ease of accessible compared to other types of MSCs. Hence, the main goal of our study was to explore the impacts of OE-MSCs transplantation on behavioral, structural, and histological deficiencies in a rat model of CA. After obtained an informed consent from volunteers, OE-MSCs were obtained from their nasal cavity. Then, OE-MSCs were characterized by the positive expression of CD73, CD90, and CD105 as MSCs as well as nestin and vimentin as primitive neuroectodermal stem cells markers. Then, the animals were randomized into three control, 3-acetylpyridine (3-AP) treated, and 3-AP + cell groups. In both experimental groups, the rats received intraperitoneal injection of 3-AP (75 mg/kg), followed by the implantation of OE-MSCs into the cerebellum of 3-AP + cell group. The impact of engrafted OE-MSCs on motor coordination and performance along with biochemical, immunohistochemical, and stereological changes in the cerebellum of the rat models of CA were investigated. According to our findings, the administration of 3-AP decreased the cerebellar GSH concentration. The injection of 3-AP also altered the morphological characteristics of the cerebellar Golgi cells. On the other hand, OE‐MSCs transplantation improved motor coordination in CA. Besides, the implantation of OE‐MSCs reduced caspase-3 expression and microglia proliferation in the cerebellum upon 3-AP administration. Finally, the transplant of OE‐MSCs protected Purkinje cells against 3-AP toxicity. In sum, the present study revealed considerable advantages of OE-MSCs in managing CA animal model.

The Hematopoietic Stem Cells of α-Thalassemic Mice

AbstractThe α-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not α-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more α-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in α-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/ + mice. In unirradiated α-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated α-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the α-thalassemic mouse is a good model for cell replacement therapy.

The hematopoietic stem cells of alpha-thalassemic mice

The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy.