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Human cord blood CD34+ cells and behavioral recovery following focal cerebral ischemia in rats

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Nystedt J., Makinen S., LaineJ., Jolkkonen J.
Acta Neurobiologiae Experimentalis
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2006
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vol. 66
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issue 4
293-300
EN
The present study investigated effects of human umbilical cord blood derived CD34+ cells on sensorimotor, cognitive, and histological outcome in rats following focal cerebral ischemia. Halothane anesthetized adult male Wistar rats were subjected to transient or permanent occlusion of the middle cerebral artery (MCAO) followed by intravenous administration of CD34+ cells (5 ? 105 or 2 ? 106) after 24 h recovery. The beam-walking and cylinder tests were used to assess sensorimotor function, and Morris water-maze examined cognitive performance during a 25 day follow-up period. Subsequently, rats were perfused for measurement of infarct volumes and detection of CD34+ cells in the brain by immunohistochemistry (MAB1281). MCAO rats showed minor or no spontaneous recovery in sensorimotor function during the follow-up. The recovery profile was similar in MCAO controls and in MCAO rats that received CD34+ cells, although CD34+ cells seemed to improve the use of impaired forelimb. There was also a trend toward improved water-maze performance by CD34+ cells in transient MCAO rats. Infarct volumes assessed from Nissl-stained sections on postoperative day 25 did not differ between the experimental groups. MAB1281-positive cells were not detected in the brain of MCAO rats that received CD34+ cells. The present study suggests that CD34+ cells might improve functional outcome in MCAO rats after systemic administration, but do not significantly provide neuroprotection.
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Embryonic-like stem cells from umbilical cord blood and potential for neural modeling

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McGuckin C., Forraz N., Baradez M.-O., Basford C., Dickinson A. M., Navran S., Hartgerink J. D.
Acta Neurobiologiae Experimentalis
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2006
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vol. 66
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issue 4
321-329
EN
Stem cells offer the distinct prospect of changing the face of human medicine. However, although they have potential to form different tissues, are still in the early stages of development as therapeutic interventions. The three most used stem cell sources are umbilical cord blood, bone marrow and human embryos. Whilst, cord blood is now used to treat over 70 disorders, at the time of writing this manuscript, not a single disease has been overcome or ameliorated using human embryonic stem cells. Advancing stem cell medicine requires ethically sound and scientifically robust models to develop tomorrow's medicines. Media attention, however, distracts from this reality; it is important to remember that stem cells are a new visitor to the medical world and require more research. Here we describe the utility of human cord blood to develop neural models that are necessary to take stem cells to the next level ? into human therapies.
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Patterned growth and differentiation of human cord blood- derived neural stem cells on bio-functionalized surfaces

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Buzanska L., Ruiz A., Zychowicz M., Rauscher H., Ceriotti L., Rossi F., Colpo P., Domanska-Janik K., Coecke S.
Acta Neurobiologiae Experimentalis
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2009
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vol. 69
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issue 1
24-36
EN
Bio-functionalized surfaces were prepared to study the adherence and differentiation capacity of neural stem cells derived from human umbilical cord blood (HUCB-NSC). Cell growth platforms containing arranged arrays of adhesive molecules were created by microcontact printing on a biologically inert surface. Biomolecules used to prepare microarray platforms included the extracellular matrix protein fibronectin and the polyaminoacid poly-L-lysine. HUCB-NSC plated on microplatforms at various serum conditions showed serum and molecule type dependent capacity for adhesion and differentiation. Poly-L-lysine allowed the maintenance of stem-like non differentiated cells attached to the surface, whereas fibronectin promoted spreading and neural commitment. Serum deprivation did not influence the attachment of HUCB-NSC to fibronectin, but significantly enhanced the attachment to poly-L-lysine and promoted dBcAMP induced neuronal differentiation. A bio-pattern of squares with interconnecting lines was used to guide neuronal differentiation by directing cell protrusion outgrowth. Tailoring the geometry of the bio-pattern enabled directing and monitoring of the neural stem cells. development in the large scale multiparameter biotests.
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Neural commitment of cord blood stem cells (HUCB-NSC/NP): Therapeutic perspectives

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Domanska-Janik K., Habich A., Sarnowska A., Janowski M.
Acta Neurobiologiae Experimentalis
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2006
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vol. 66
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issue 4
279-291
EN
Human umbilical cord blood (HUCB) is considered a promising source of neural progenitors capable of being used for cellular therapies in neurological disorders. Here we review briefly our work on the elucidation of mechanisms and development of practical standards as regards the selection, maintenance and use of cord blood derivatives for such purposes. Our results join those of other recent studies in suggesting strongly that, the generation of neural-like cells from tissue belonging to a different germ layer (such as a cord blood is) is most probably explained by reference to a discrete subpopulation of embryonic-like stem cells of pluripotent characteristics. Such cells identified in cord blood through their expression of specific genetic and protein markers can be expanded in vitro and directed toward neurally-committed progenitors differentiating further into more mature neuron-like or macroglia-like cell phenotypes. From this HUCB-derived neural progenitor fraction a novel neural-like stem cell line (HUCB-NSC) has been developed, and characterized in respect of in vitro and in vivo (post-transplantation) properties.
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Defined serum-free culturing conditions for neural tissue engineering of human cord blood stem cells

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Ali H., Jurga M., Kurgonaite K., Forraz N., McGuckin C.
Acta Neurobiologiae Experimentalis
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2009
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vol. 69
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issue 1
12-23
EN
Taking tissue engineering applications into clinical trials requires the development of efficient and safe protocols incorporated with effective 3-dimentional cell culturing and differentiation systems in order to develop transplantable tissues that may offer a life-line for patients in the future. Cord blood, which is perhaps the most abundant world stem cell source, has shown previously practical and ethical advantages over other stem cells sources in many research and clinical applications including regenerative medicine. We previously developed a three-step protocol for isolation, expansion and sequential neuronal differentiation of cord blood pluripotent stem cells (characterized with our unique triple immunocytochemisty scheme for Oct-4, Sox-2 and Nanog) in defined serum-free culturing conditions. In this study we incorporated this protocol with 3-dimentional culturing systems which produced artificial neuronal tissues expressing Nestin, NF-200, TUJ1, PSD-95 and NeuN. We showed that cord blood pluripotent stem cells are a potential and promising candidate for future neural tissue engineering and regenerative medicine.
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Human cord blood cells can differentiate into retinal nerve cells

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Koike-Kiriyama N., Adachi Y., Minamino K., Iwasaki M., Nakano K., Koike Y., Yamada H., Mukaide H., Shigematsu A., Mizokami T., Matsumura M., Ikehara S.
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EN
Retinal degeneration and dystrophy are the major causes of blindness in the developed world. It has been reported that human cord blood cells (HCBCs) can differentiate into neuron-like cells in vitro. We have recently demonstrated that bone marrow cells (BMCs) of both mice and rats can differentiate into retinal nerve cells (RNCs). In the present study, we show the differentiation capacity of HCBCs into RNCs in vivo. We transplanted lineage-negative HCBCs into the subretinal space of severe combined immunodeficiency (SCID) mice. Two weeks after the transplantation, some of the transplanted cells expressed human nestin, human MAP2, human neuron specific enolase (NSE), beta-III tubulin and also rhodopsin. These results indicate that HCBCs can differentiate into RNCs and suggest that our new strategy could be used for the regeneration of retinal nerve cells in degenerative or dystrophic diseases.
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Lack of migration and neurological benefits after infusion of umbilical cord blood cells in ischemic brain injury

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Zawadzka M., Lukasiuk K., Machaj E. K., Pojda Z., Kaminska B.
Acta Neurobiologiae Experimentalis
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2009
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vol. 69
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issue 1
46-51
EN
The finding of stem/progenitor cells in postnatal bone marrow and umbilical cord blood, opens up a possibility of using stem cells to treat neurologic diseases. There is a controversy, whether intravenously administered human umbilical cord blood cells (HUCBC) migrate to the brain, differentiate and improve recovery after ischemia. In this study, 1-3 ?10^6 cells from non-cultured (non-committed) mononuclear HUCBC fraction were intravenously infused 1, 2, 3 or 7 days after a transient middle cerebral artery occlusion (MCAo) in adult rats. We found few human cells only in the ischemic area, localized mostly around blood vessels with few positive cells in the brain parenchyma. Timing of HUCBC delivery after ischemia or injection of Cyclosporin A at the time of delivery, had no effect on the number of human cells detected in the ischemic brain. Infusion of HUCBC did not reduce infarct volume and did not improve neurologic deficits after MCAo, suggesting that HUCBC failed to migrate/survive in the ischemic brain and did not provide significant neurological benefits.
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