%0 Journal Article %1 Reich.2008 %A Reich, Doreen M. %A Hau, Susann %A Stahl, Tobias %A Scholz, Markus %A Naumann, Wilfried %A Emmrich, Frank %A Boltze, Johannes %A Kamprad, Manja %D 2008 %J BMC neuroscience %K Antigens,_CD/analysis Apoptosis Cell_Differentiation Cell_Hypoxia Cell_Line,_Tumor Cells,_Cultured Chemokines/analysis/biosynthesis Coculture_Techniques/methods Fetal_Blood/cytology/immunology/metabolism Flow_Cytometry Glycoproteins/analysis Hematopoietic_Stem_Cells/cytology/immunology/metabolism Humans Infant,_Newborn Intercellular_Signaling_Peptides_and_Proteins/analysis/biosynthesis Leukocytes,_Mononuclear/cytology/immunology/metabolism Microscopy,_Fluorescence Neuroblastoma/immunology/metabolism/pathology Neurons/metabolism/pathology Peptides/analysis %P 91 %T Neuronal hypoxia in vitro: investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells %V 9 %X BACKGROUND\r\nThe therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood.\r\nMETHODS\r\nA human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38\% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06\% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array.\r\nRESULTS\r\ntMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7\% +/- 3\%). Untreated post-hypoxic control cultures showed apoptosis rates of 85\% +/- 11\%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures.\r\nCONCLUSION\r\nOur data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes.

@article{Reich.2008, abstract = {BACKGROUND\r\nThe therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood.\r\nMETHODS\r\nA human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38\% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06\% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array.\r\nRESULTS\r\ntMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7\% +/- 3\%). Untreated post-hypoxic control cultures showed apoptosis rates of 85\% +/- 11\%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures.\r\nCONCLUSION\r\nOur data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes.}, added-at = {2014-10-15T15:04:19.000+0200}, author = {Reich, Doreen M. and Hau, Susann and Stahl, Tobias and Scholz, Markus and Naumann, Wilfried and Emmrich, Frank and Boltze, Johannes and Kamprad, Manja}, biburl = {https://www.bibsonomy.org/bibtex/22e9c73cba4823e7df3526722b476ba78/drtester}, interhash = {06e3ec70049399dbd4da87de5269bf50}, intrahash = {2e9c73cba4823e7df3526722b476ba78}, journal = {BMC neuroscience}, keywords = {Antigens,_CD/analysis Apoptosis Cell_Differentiation Cell_Hypoxia Cell_Line,_Tumor Cells,_Cultured Chemokines/analysis/biosynthesis Coculture_Techniques/methods Fetal_Blood/cytology/immunology/metabolism Flow_Cytometry Glycoproteins/analysis Hematopoietic_Stem_Cells/cytology/immunology/metabolism Humans Infant,_Newborn Intercellular_Signaling_Peptides_and_Proteins/analysis/biosynthesis Leukocytes,_Mononuclear/cytology/immunology/metabolism Microscopy,_Fluorescence Neuroblastoma/immunology/metabolism/pathology Neurons/metabolism/pathology Peptides/analysis}, pages = 91, timestamp = {2014-10-15T15:04:19.000+0200}, title = {Neuronal hypoxia in vitro: investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells}, volume = 9, year = 2008 }