Exploring the neurogenic differentiation of human dental pulp stem cells.
Human dental pulp stem cells (hDPSCs) have increasingly gained interest as a potential therapy for nerve regeneration in medicine and dentistry, however their neurogenic potential remains a matter of debate. This study aimed to characterize hDPSC neuronal differentiation in comparison with the human...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0277134 |
| _version_ | 1798015496111521792 |
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| author | Arwa A Al-Maswary Molly O'Reilly Andrew P Holmes A Damien Walmsley Paul R Cooper Ben A Scheven |
| author_facet | Arwa A Al-Maswary Molly O'Reilly Andrew P Holmes A Damien Walmsley Paul R Cooper Ben A Scheven |
| author_sort | Arwa A Al-Maswary |
| collection | DOAJ |
| description | Human dental pulp stem cells (hDPSCs) have increasingly gained interest as a potential therapy for nerve regeneration in medicine and dentistry, however their neurogenic potential remains a matter of debate. This study aimed to characterize hDPSC neuronal differentiation in comparison with the human SH-SY5Y neuronal stem cell differentiation model. Both hDPSCs and SH-SY5Y could be differentiated to generate typical neuronal-like cells following sequential treatment with all-trans retinoic acid (ATRA) and brain-derived neurotrophic factor (BDNF), as evidenced by significant expression of neuronal proteins βIII-tubulin (TUBB3) and neurofilament medium (NF-M). Both cell types also expressed multiple neural gene markers including growth-associated protein 43 (GAP43), enolase 2/neuron-specific enolase (ENO2/NSE), synapsin I (SYN1), nestin (NES), and peripherin (PRPH), and exhibited measurable voltage-activated Na+ and K+ currents. In hDPSCs, upregulation of acetylcholinesterase (ACHE), choline O-acetyltransferase (CHAT), sodium channel alpha subunit 9 (SCN9A), POU class 4 homeobox 1 (POU4F1/BRN3A) along with a downregulation of motor neuron and pancreas homeobox 1 (MNX1) indicated that differentiation was more guided toward a cholinergic sensory neuronal lineage. Furthermore, the Extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 significantly impaired hDPSC neuronal differentiation and was associated with reduction of the ERK1/2 phosphorylation. In conclusion, this study demonstrates that extracellular signal-regulated kinase/Mitogen-activated protein kinase (ERK/MAPK) is necessary for sensory cholinergic neuronal differentiation of hDPSCs. hDPSC-derived cholinergic sensory neuronal-like cells represent a novel model and potential source for neuronal regeneration therapies. |
| first_indexed | 2024-04-11T15:35:31Z |
| format | Article |
| id | doaj.art-384cfbc9348a414882d60b4b002b6dbf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T15:35:31Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-384cfbc9348a414882d60b4b002b6dbf2022-12-22T04:16:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011711e027713410.1371/journal.pone.0277134Exploring the neurogenic differentiation of human dental pulp stem cells.Arwa A Al-MaswaryMolly O'ReillyAndrew P HolmesA Damien WalmsleyPaul R CooperBen A SchevenHuman dental pulp stem cells (hDPSCs) have increasingly gained interest as a potential therapy for nerve regeneration in medicine and dentistry, however their neurogenic potential remains a matter of debate. This study aimed to characterize hDPSC neuronal differentiation in comparison with the human SH-SY5Y neuronal stem cell differentiation model. Both hDPSCs and SH-SY5Y could be differentiated to generate typical neuronal-like cells following sequential treatment with all-trans retinoic acid (ATRA) and brain-derived neurotrophic factor (BDNF), as evidenced by significant expression of neuronal proteins βIII-tubulin (TUBB3) and neurofilament medium (NF-M). Both cell types also expressed multiple neural gene markers including growth-associated protein 43 (GAP43), enolase 2/neuron-specific enolase (ENO2/NSE), synapsin I (SYN1), nestin (NES), and peripherin (PRPH), and exhibited measurable voltage-activated Na+ and K+ currents. In hDPSCs, upregulation of acetylcholinesterase (ACHE), choline O-acetyltransferase (CHAT), sodium channel alpha subunit 9 (SCN9A), POU class 4 homeobox 1 (POU4F1/BRN3A) along with a downregulation of motor neuron and pancreas homeobox 1 (MNX1) indicated that differentiation was more guided toward a cholinergic sensory neuronal lineage. Furthermore, the Extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 significantly impaired hDPSC neuronal differentiation and was associated with reduction of the ERK1/2 phosphorylation. In conclusion, this study demonstrates that extracellular signal-regulated kinase/Mitogen-activated protein kinase (ERK/MAPK) is necessary for sensory cholinergic neuronal differentiation of hDPSCs. hDPSC-derived cholinergic sensory neuronal-like cells represent a novel model and potential source for neuronal regeneration therapies.https://doi.org/10.1371/journal.pone.0277134 |
| spellingShingle | Arwa A Al-Maswary Molly O'Reilly Andrew P Holmes A Damien Walmsley Paul R Cooper Ben A Scheven Exploring the neurogenic differentiation of human dental pulp stem cells. PLoS ONE |
| title | Exploring the neurogenic differentiation of human dental pulp stem cells. |
| title_full | Exploring the neurogenic differentiation of human dental pulp stem cells. |
| title_fullStr | Exploring the neurogenic differentiation of human dental pulp stem cells. |
| title_full_unstemmed | Exploring the neurogenic differentiation of human dental pulp stem cells. |
| title_short | Exploring the neurogenic differentiation of human dental pulp stem cells. |
| title_sort | exploring the neurogenic differentiation of human dental pulp stem cells |
| url | https://doi.org/10.1371/journal.pone.0277134 |
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