30 research outputs found
Intrathecal injection of human umbilical cord blood-derived mesenchymal stem cells for the treatment of basilar artery dissection: a case report
<p>Abstract</p> <p>Introduction</p> <p>Basilar artery dissection is a rare occurrence, and is significantly associated with morbidity and mortality. To the best of our knowledge, we report the first case of basilar artery dissection treated with mesenchymal stem cells.</p> <p>Case presentation</p> <p>We present the case of a 17-year-old Korean man who was diagnosed with basilar artery dissection. Infarction of the bilateral pons, midbrain and right superior cerebellum due to his basilar artery dissection was partially recanalized by intrathecal injection of human umbilical cord blood-derived mesenchymal stem cells. No immunosuppressants were given to our patient, and human leukocyte antigen alloantibodies were not detected after cell therapy.</p> <p>Conclusions</p> <p>This case indicates that intrathecal injections of mesenchymal stem cells can be used in the treatment of basilar artery dissection.</p
Human Umbilical Cord Blood Treatment in a Mouse Model of ALS: Optimization of Cell Dose
Amyotrophic Lateral Sclerosis (ALS) is a multicausal disease characterized by motor neuron degeneration in the spinal cord and brain. Cell therapy may be a promising new treatment for this devastating disorder. We recently showed that a single low dose (10(6) cells) of mononuclear human umbilical cord blood (MNC hUCB) cells administered intravenously to G93A mice delayed symptom progression and modestly prolonged lifespan. The aim of this pre-clinical translation study is to optimize the dose of MNC hUCB cells to retard disease progression in G93A mice. Three different doses of MNC hUCB cells, 10x10(6), 25x10(6) and 50x10(6), were administered intravenously into pre-symptomatic G93A mice. Motor function tests and various assays to determine cell effects were performed on these mice.Our results showed that a cell dose of 25x10(6) cells significantly increased lifespan of mice by 20-25% and delayed disease progression by 15%. The most beneficial effect on decreasing pro-inflammatory cytokines in the brain and spinal cord was found in this group of mice. Human Th2 cytokines were found in plasma of mice receiving 25x10(6) cells, although prevalent human Th1 cytokines were indicated in mice with 50x10(6) cells. High response of splenic cells to mitogen (PHA) was indicated in mice receiving 25x10(6) (mainly) and 10x10(6) cells. Significantly increased lymphocytes and decreased neutrophils in the peripheral blood were found only in animals receiving 25x10(6) cells. Stable reduction in microglia density in both cervical and lumbar spinal cords was also noted in mice administered with 25x10(6) cells.These results demonstrate that treatment for ALS with an appropriate dose of MNC hUCB cells may provide a neuroprotective effect for motor neurons through active involvement of these cells in modulating the host immune inflammatory system response
Interactive histogenesis of axonal strata and proliferative zones in the human fetal cerebral wall
Development of the cerebral wall is characterized by partially overlapping histogenetic events. However, little is known with regards to when, where, and how growing axonal pathways interact with progenitor cell lineages in the proliferative zones of the human fetal cerebrum. We analyzed the developmental continuity and spatial distribution of the axonal sagittal strata (SS) and their relationship with proliferative zones in a series of human brains (8-40 post-conceptional weeks; PCW) by comparing histological, histochemical, and immunocytochemical data with magnetic resonance imaging (MRI). Between 8.5 and 11 PCW, thalamocortical fibers from the intermediate zone (IZ) were initially dispersed throughout the subventricular zone (SVZ), while sizeable axonal "invasion" occurred between 12.5 and 15 PCW followed by callosal fibers which "delaminated" the ventricular zone-inner SVZ from the outer SVZ (OSVZ). During midgestation, the SS extensively invaded the OSVZ, separating cell bands, and a new multilaminar axonal-cellular compartment (MACC) was formed. Preterm period reveals increased complexity of the MACC in terms of glial architecture and the thinning of proliferative bands. The addition of associative fibers and the formation of the centrum semiovale separated the SS from the subplate. In vivo MRI of the occipital SS indicates a "triplet" structure of alternating hypointense and hyperintense bands. Our results highlighted the developmental continuity of sagittally oriented "corridors" of projection, commissural and associative fibers, and histogenetic interaction with progenitors, neurons, and glia. Histogenetical changes in the MACC, and consequently, delineation of the SS on MRI, may serve as a relevant indicator of white matter microstructural integrity in the developing brain
Human Umbilical Cord Blood Stem Cells Infusion in Spinal Cord Injury: Engraftment and Beneficial Influence on Behavior
Human Umbilical Cord Blood–Derived Mesenchymal Stem Cells Do Not Differentiate Into Neural Cell Types or Integrate Into the Retina After Intravitreal Grafting in Neonatal Rats
Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain development
Targeted deletion of two members of the FE65 family of adaptor proteins, FE65 and FE65L1, results in cortical dysplasia. Heterotopias resembling those found in cobblestone lissencephalies in which neuroepithelial cells migrate into superficial layers of the developing cortex, aberrant cortical projections and loss of infrapyramidal mossy fibers arise in FE65/FE65L1 compound null animals, but not in single gene knockouts. The disruption of pial basal membranes underlying the heterotopias and poor organization of fibrillar laminin by isolated meningeal fibroblasts from double knockouts suggests that FE65 proteins are involved in basement membrane assembly. A similar phenotype is observed in triple mutant mice lacking the APP family members APP, APLP1 and APLP2, all of which interact with FE65 proteins, suggesting that this phenotype may be caused by decreased transmission of an APP-dependent signal through the FE65 proteins. The defects observed in the double knockout may also involve the family of Ena/Vasp proteins, which participate in actin cytoskeleton remodeling and interact with the WW domains of FE65 proteins
Anti-inflammatory Effects of Human Cord Blood Cells in a Rat Model of Stroke
When human umbilical cord blood cells (HUCBCs) are administered intravenously after a middle cerebral artery occlusion, they reliably produce behavioral and anatomical recovery, and protect neural tissue from progressive change. However, our results indicate that the cells do not exert their effects by engraftment in the peri-infarct region, even though they migrate to the site of injury. The objective of the present study was to determine if the cells induce recovery by decreasing inflammation. We used a combination of in vivo and in vitro studies to show that HUCBCs decrease inflammation in the brain after stroke and thereby enhance neuroprotection. After stroke and transplantation, there was a decrease in CD45/CD11b- and CD45/B220-positive (+) cells. This decrease was accompanied by a decrease in mRNA and protein expression of pro-inflammatory cytokines and a decrease in nuclear factor kappaB (NF-kappaB) DNA binding activity in the brain of stroke animals treated with HUCBCs. In addition to modulating the inflammatory response, we demonstrate that the cord blood cells increase neuronal survival through non-immune mechanisms. Once thought of as cell replacement therapy, we now propose that cord blood treatment in stroke reduces inflammation and provides neuroprotection. Both of these components are necessary for effective therapy