Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines

Rat progenitor cells from the germinal region of the fetal mesencephalon were isolated and expanded in media containing the mitogen epidermal growth factor. These cells remained mitotically active (up to 8 months), were immunoreactive for the progenitor cell marker nestin, and were readily infected...

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Veröffentlicht in:Experimental neurology 1998-02, Vol.149 (2), p.411-423
Hauptverfasser: Ling, Zao Dung, Potter, Elizabeth D., Lipton, Jack W., Carvey, Paul M.
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Lipton, Jack W.
Carvey, Paul M.
description Rat progenitor cells from the germinal region of the fetal mesencephalon were isolated and expanded in media containing the mitogen epidermal growth factor. These cells remained mitotically active (up to 8 months), were immunoreactive for the progenitor cell marker nestin, and were readily infected with the BAGα retrovirus. When incubated in complete media containing serum in poly-l-lysine-coated plates, these cells spontaneously converted to neurons and glia but rarely expressed the dopamine (DA) neuron phenotype. Nineteen different cytokines were screened for their ability to induce the DA phenotype and only interleukin (IL)-1 was found to induce the expression of the DA neuron marker tyrosine hydroxylase (TH). The addition of IL-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) were found to further increase the number of TH immunoreactive (TH-ir) cells. The addition of mesencephalic membrane fragments and striatal culture-conditioned media along with the cytokine mixture induced the expression of morphologically mature TH-ir cells that were also immunoreactive for dopa-decarboxylase, the DA transporter, and DA itself. The DA neuron cell counts were approximately 20–25% of the overall cell population and 50% of the neurofilament population. Astrocytes and oligodendrocytes were also present. These data suggest that hematopoietic cytokines participate in the development of the DA neuron phenotype. Parallels between the function of hematopoietic cytokines in bone marrow and the central nervous system may exist and be useful in understanding the factors which regulate the differentiation of neurons in the brain.
doi_str_mv 10.1006/exnr.1998.6715
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The addition of mesencephalic membrane fragments and striatal culture-conditioned media along with the cytokine mixture induced the expression of morphologically mature TH-ir cells that were also immunoreactive for dopa-decarboxylase, the DA transporter, and DA itself. The DA neuron cell counts were approximately 20–25% of the overall cell population and 50% of the neurofilament population. Astrocytes and oligodendrocytes were also present. These data suggest that hematopoietic cytokines participate in the development of the DA neuron phenotype. 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These cells remained mitotically active (up to 8 months), were immunoreactive for the progenitor cell marker nestin, and were readily infected with the BAGα retrovirus. When incubated in complete media containing serum in poly-l-lysine-coated plates, these cells spontaneously converted to neurons and glia but rarely expressed the dopamine (DA) neuron phenotype. Nineteen different cytokines were screened for their ability to induce the DA phenotype and only interleukin (IL)-1 was found to induce the expression of the DA neuron marker tyrosine hydroxylase (TH). The addition of IL-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) were found to further increase the number of TH immunoreactive (TH-ir) cells. The addition of mesencephalic membrane fragments and striatal culture-conditioned media along with the cytokine mixture induced the expression of morphologically mature TH-ir cells that were also immunoreactive for dopa-decarboxylase, the DA transporter, and DA itself. The DA neuron cell counts were approximately 20–25% of the overall cell population and 50% of the neurofilament population. Astrocytes and oligodendrocytes were also present. These data suggest that hematopoietic cytokines participate in the development of the DA neuron phenotype. 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Transplantation</subject><subject>differentiation</subject><subject>Dopa Decarboxylase - biosynthesis</subject><subject>Dopamine - metabolism</subject><subject>dopamine neurons</subject><subject>Dopamine Plasma Membrane Transport Proteins</subject><subject>Embryo, Mammalian</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>Erythropoietin - pharmacology</subject><subject>Fibroblast Growth Factor 2 - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glial Cell Line-Derived Neurotrophic Factor</subject><subject>Growth Inhibitors - pharmacology</subject><subject>Interleukin-1 - pharmacology</subject><subject>Interleukin-11 - pharmacology</subject><subject>Interleukin-6</subject><subject>Leukemia Inhibitory Factor</subject><subject>Lymphokines - pharmacology</subject><subject>Membrane Glycoproteins</subject><subject>Membrane Transport Proteins</subject><subject>mesencephalon</subject><subject>Mesencephalon - cytology</subject><subject>Mesencephalon - embryology</subject><subject>Nerve Growth Factors</subject><subject>Nerve Tissue Proteins - pharmacology</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Oligodendroglia - cytology</subject><subject>progenitor cells</subject><subject>Rats</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - drug effects</subject><subject>Tyrosine 3-Monooxygenase - biosynthesis</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kDtPwzAQgC0EglJY2ZAyILYUv5LYIypPidcAEpvlOOdiSO1ip4j-exK16sZ0p7vvHvoQOiF4QjAuL-DXxwmRUkzKihQ7aESwxDnlDO-iEcaE51yI8gAdpvSJMZacVvtoXxZ9WvARer9y1kIE3zndueCzYLNHSOANLD5060z2EsMMvOtCzKbQtilzvgvZVVjoufMQZz3yBMsYfMrqVTZddeGrr6cjtGd1m-B4E8fo7eb6dXqXPzzf3k8vH3LDStHlwlaSNWWlLWfGcqoZCAJNRQ0GJhthmAFZkprbmjFb1bg2uqCFoFRLo3HDxuh8vXcRw_cSUqfmLpn-Ue0hLJOqZEUL0h8Zo8kaNDGkFMGqRXRzHVeKYDWoVINKNahUg8p-4HSzeVnPodniG3d9_2zT18no1kbtjUtbjBLJOB8wscagt_DjIKpk3OC3cRFMp5rg_vvgD23ZkW0</recordid><startdate>19980201</startdate><enddate>19980201</enddate><creator>Ling, Zao Dung</creator><creator>Potter, Elizabeth D.</creator><creator>Lipton, Jack W.</creator><creator>Carvey, Paul M.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19980201</creationdate><title>Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines</title><author>Ling, Zao Dung ; Potter, Elizabeth D. ; Lipton, Jack W. ; Carvey, Paul M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-8f793d67af43cf42a3e81ed72c0e39d8c3ce961b4fb33f7b0bca525822a9ca0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Astrocytes - cytology</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Membrane - physiology</topic><topic>Cells, Cultured</topic><topic>Corpus Striatum - physiology</topic><topic>Culture Media, Conditioned</topic><topic>cytokines</topic><topic>Cytokines - pharmacology</topic><topic>Development. Senescence. Regeneration. Transplantation</topic><topic>differentiation</topic><topic>Dopa Decarboxylase - biosynthesis</topic><topic>Dopamine - metabolism</topic><topic>dopamine neurons</topic><topic>Dopamine Plasma Membrane Transport Proteins</topic><topic>Embryo, Mammalian</topic><topic>Epidermal Growth Factor - pharmacology</topic><topic>Erythropoietin - pharmacology</topic><topic>Fibroblast Growth Factor 2 - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glial Cell Line-Derived Neurotrophic Factor</topic><topic>Growth Inhibitors - pharmacology</topic><topic>Interleukin-1 - pharmacology</topic><topic>Interleukin-11 - pharmacology</topic><topic>Interleukin-6</topic><topic>Leukemia Inhibitory Factor</topic><topic>Lymphokines - pharmacology</topic><topic>Membrane Glycoproteins</topic><topic>Membrane Transport Proteins</topic><topic>mesencephalon</topic><topic>Mesencephalon - cytology</topic><topic>Mesencephalon - embryology</topic><topic>Nerve Growth Factors</topic><topic>Nerve Tissue Proteins - pharmacology</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Oligodendroglia - cytology</topic><topic>progenitor cells</topic><topic>Rats</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - drug effects</topic><topic>Tyrosine 3-Monooxygenase - biosynthesis</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ling, Zao Dung</creatorcontrib><creatorcontrib>Potter, Elizabeth D.</creatorcontrib><creatorcontrib>Lipton, Jack W.</creatorcontrib><creatorcontrib>Carvey, Paul M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ling, Zao Dung</au><au>Potter, Elizabeth D.</au><au>Lipton, Jack W.</au><au>Carvey, Paul M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>1998-02-01</date><risdate>1998</risdate><volume>149</volume><issue>2</issue><spage>411</spage><epage>423</epage><pages>411-423</pages><issn>0014-4886</issn><eissn>1090-2430</eissn><coden>EXNEAC</coden><abstract>Rat progenitor cells from the germinal region of the fetal mesencephalon were isolated and expanded in media containing the mitogen epidermal growth factor. These cells remained mitotically active (up to 8 months), were immunoreactive for the progenitor cell marker nestin, and were readily infected with the BAGα retrovirus. When incubated in complete media containing serum in poly-l-lysine-coated plates, these cells spontaneously converted to neurons and glia but rarely expressed the dopamine (DA) neuron phenotype. Nineteen different cytokines were screened for their ability to induce the DA phenotype and only interleukin (IL)-1 was found to induce the expression of the DA neuron marker tyrosine hydroxylase (TH). The addition of IL-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) were found to further increase the number of TH immunoreactive (TH-ir) cells. The addition of mesencephalic membrane fragments and striatal culture-conditioned media along with the cytokine mixture induced the expression of morphologically mature TH-ir cells that were also immunoreactive for dopa-decarboxylase, the DA transporter, and DA itself. The DA neuron cell counts were approximately 20–25% of the overall cell population and 50% of the neurofilament population. Astrocytes and oligodendrocytes were also present. These data suggest that hematopoietic cytokines participate in the development of the DA neuron phenotype. Parallels between the function of hematopoietic cytokines in bone marrow and the central nervous system may exist and be useful in understanding the factors which regulate the differentiation of neurons in the brain.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>9500954</pmid><doi>10.1006/exnr.1998.6715</doi><tpages>13</tpages></addata></record>
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subjects Animals
Astrocytes - cytology
Biological and medical sciences
Biomarkers
Carrier Proteins - metabolism
Cell Differentiation - drug effects
Cell Membrane - physiology
Cells, Cultured
Corpus Striatum - physiology
Culture Media, Conditioned
cytokines
Cytokines - pharmacology
Development. Senescence. Regeneration. Transplantation
differentiation
Dopa Decarboxylase - biosynthesis
Dopamine - metabolism
dopamine neurons
Dopamine Plasma Membrane Transport Proteins
Embryo, Mammalian
Epidermal Growth Factor - pharmacology
Erythropoietin - pharmacology
Fibroblast Growth Factor 2 - pharmacology
Fundamental and applied biological sciences. Psychology
Glial Cell Line-Derived Neurotrophic Factor
Growth Inhibitors - pharmacology
Interleukin-1 - pharmacology
Interleukin-11 - pharmacology
Interleukin-6
Leukemia Inhibitory Factor
Lymphokines - pharmacology
Membrane Glycoproteins
Membrane Transport Proteins
mesencephalon
Mesencephalon - cytology
Mesencephalon - embryology
Nerve Growth Factors
Nerve Tissue Proteins - pharmacology
Neurons - cytology
Neurons - drug effects
Neurons - physiology
Oligodendroglia - cytology
progenitor cells
Rats
Stem Cells - cytology
Stem Cells - drug effects
Tyrosine 3-Monooxygenase - biosynthesis
Vertebrates: nervous system and sense organs
title Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines
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