Differentiation of Chromaffin Progenitor Cells to Dopaminergic Neurons
The differentiation of dopamine-producing neurons from chromaffin progenitors might represent a new valuable source for replacement therapies in Parkinson's disease. However, characterization of their differentiation potential is an important prerequisite for efficient engraftment. Based on our...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-11-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368912X638874 |
| _version_ | 1818879327866978304 |
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| author | Vladimir Vukicevic Janine Schmid Andreas Hermann Sven Lange Nan Qin Linda Gebauer Kuei-Fang Chung Ursula Ravens Graeme Eisenhofer Alexander Storch Marius Ader Stefan R. Bornstein Monika Ehrhart-Bornstein Ph.D. |
| author_facet | Vladimir Vukicevic Janine Schmid Andreas Hermann Sven Lange Nan Qin Linda Gebauer Kuei-Fang Chung Ursula Ravens Graeme Eisenhofer Alexander Storch Marius Ader Stefan R. Bornstein Monika Ehrhart-Bornstein Ph.D. |
| author_sort | Vladimir Vukicevic |
| collection | DOAJ |
| description | The differentiation of dopamine-producing neurons from chromaffin progenitors might represent a new valuable source for replacement therapies in Parkinson's disease. However, characterization of their differentiation potential is an important prerequisite for efficient engraftment. Based on our previous studies on isolation and characterization of chromaffin progenitors from adult adrenals, this study investigates their potential to produce dopaminergic neurons and means to enhance their dopaminergic differentiation. Chromaffin progenitors grown in sphere culture showed an increased expression of nestin and Mash1, indicating an increase of the progenitor subset. Proneurogenic culture conditions induced the differentiation into neurons positive for neural markers β-III-tubulin, MAP2, and TH accompanied by a decrease of Mash1 and nestin. Furthermore, Notch2 expression decreased concomitantly with a downregulation of downstream effectors Hes1 and Hes5 responsible for self-renewal and proliferation maintenance of progenitor cells. Chromaffin progenitor-derived neurons secreted dopamine upon stimulation by potassium. Strikingly, treatment of differentiating cells with retinoic and ascorbic acid resulted in a twofold increase of dopamine secretion while norepinephrine and epinephrine were decreased. Initiation of dopamine synthesis and neural maturation is controlled by Pitx3 and Nurr1. Both Pitx3 and Nurr1 were identified in differentiating chromaffin progenitors. Along with the gained dopaminergic function, electrophysiology revealed features of mature neurons, such as sodium channels and the capability to fire multiple action potentials. In summary, this study elucidates the capacity of chromaffin progenitor cells to generate functional dopaminergic neurons, indicating their potential use in cell replacement therapies. |
| first_indexed | 2024-12-19T14:28:19Z |
| format | Article |
| id | doaj.art-c7b76b935fcd4119b9e7ba17d9fcad47 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-19T14:28:19Z |
| publishDate | 2012-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-c7b76b935fcd4119b9e7ba17d9fcad472022-12-21T20:17:33ZengSAGE PublishingCell Transplantation0963-68971555-38922012-11-012110.3727/096368912X638874Differentiation of Chromaffin Progenitor Cells to Dopaminergic NeuronsVladimir Vukicevic0Janine Schmid1Andreas Hermann2Sven Lange3Nan Qin4Linda Gebauer5Kuei-Fang Chung6Ursula Ravens7Graeme Eisenhofer8Alexander Storch9Marius Ader10Stefan R. Bornstein11Monika Ehrhart-Bornstein Ph.D.12Molecular Endocrinology, Medical Clinic III, University Clinic Dresden, Dresden University of Technology, Dresden, GermanyMolecular Endocrinology, Medical Clinic III, University Clinic Dresden, Dresden University of Technology, Dresden, GermanyCenter for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, GermanyMolecular Endocrinology, Medical Clinic III, University Clinic Dresden, Dresden University of Technology, Dresden, GermanyDepartments of Clinical Chemistry and Laboratory Medicine, University of Dresden, Dresden University of Technology, Dresden, GermanyMolecular Endocrinology, Medical Clinic III, University Clinic Dresden, Dresden University of Technology, Dresden, GermanyMolecular Endocrinology, Medical Clinic III, University Clinic Dresden, Dresden University of Technology, Dresden, GermanyInstitute of Toxicology and Pharmacology, Medical Faculty Dresden, Dresden University of Technology, Dresden, GermanyDepartments of Clinical Chemistry and Laboratory Medicine, University of Dresden, Dresden University of Technology, Dresden, GermanyInstitute of Toxicology and Pharmacology, Medical Faculty Dresden, Dresden University of Technology, Dresden, GermanyCenter for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, GermanyCenter for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, GermanyCenter for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, GermanyThe differentiation of dopamine-producing neurons from chromaffin progenitors might represent a new valuable source for replacement therapies in Parkinson's disease. However, characterization of their differentiation potential is an important prerequisite for efficient engraftment. Based on our previous studies on isolation and characterization of chromaffin progenitors from adult adrenals, this study investigates their potential to produce dopaminergic neurons and means to enhance their dopaminergic differentiation. Chromaffin progenitors grown in sphere culture showed an increased expression of nestin and Mash1, indicating an increase of the progenitor subset. Proneurogenic culture conditions induced the differentiation into neurons positive for neural markers β-III-tubulin, MAP2, and TH accompanied by a decrease of Mash1 and nestin. Furthermore, Notch2 expression decreased concomitantly with a downregulation of downstream effectors Hes1 and Hes5 responsible for self-renewal and proliferation maintenance of progenitor cells. Chromaffin progenitor-derived neurons secreted dopamine upon stimulation by potassium. Strikingly, treatment of differentiating cells with retinoic and ascorbic acid resulted in a twofold increase of dopamine secretion while norepinephrine and epinephrine were decreased. Initiation of dopamine synthesis and neural maturation is controlled by Pitx3 and Nurr1. Both Pitx3 and Nurr1 were identified in differentiating chromaffin progenitors. Along with the gained dopaminergic function, electrophysiology revealed features of mature neurons, such as sodium channels and the capability to fire multiple action potentials. In summary, this study elucidates the capacity of chromaffin progenitor cells to generate functional dopaminergic neurons, indicating their potential use in cell replacement therapies.https://doi.org/10.3727/096368912X638874 |
| spellingShingle | Vladimir Vukicevic Janine Schmid Andreas Hermann Sven Lange Nan Qin Linda Gebauer Kuei-Fang Chung Ursula Ravens Graeme Eisenhofer Alexander Storch Marius Ader Stefan R. Bornstein Monika Ehrhart-Bornstein Ph.D. Differentiation of Chromaffin Progenitor Cells to Dopaminergic Neurons Cell Transplantation |
| title | Differentiation of Chromaffin Progenitor Cells to Dopaminergic Neurons |
| title_full | Differentiation of Chromaffin Progenitor Cells to Dopaminergic Neurons |
| title_fullStr | Differentiation of Chromaffin Progenitor Cells to Dopaminergic Neurons |
| title_full_unstemmed | Differentiation of Chromaffin Progenitor Cells to Dopaminergic Neurons |
| title_short | Differentiation of Chromaffin Progenitor Cells to Dopaminergic Neurons |
| title_sort | differentiation of chromaffin progenitor cells to dopaminergic neurons |
| url | https://doi.org/10.3727/096368912X638874 |
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