A microfluidic platform to study the effects of GDNF on neuronal axon entrapment
•Microfluidic device recapitulates the axon entrapment in the “candy-store” effect.•GDNF-overexpressing SCs induce axon entrapment in the device as seen in vivo.•High concentration of GDNF is sufficient to induce axon entrapment. One potential treatment strategy to enhance axon regeneration is trans...
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| Veröffentlicht in: | Journal of neuroscience methods 2018-10, Vol.308, p.183-191 |
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| container_title | Journal of neuroscience methods |
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| creator | Wang, Ze Zhong Wood, Matthew D. Mackinnon, Susan E. Sakiyama-Elbert, Shelly E. |
| description | •Microfluidic device recapitulates the axon entrapment in the “candy-store” effect.•GDNF-overexpressing SCs induce axon entrapment in the device as seen in vivo.•High concentration of GDNF is sufficient to induce axon entrapment.
One potential treatment strategy to enhance axon regeneration is transplanting Schwann Cells (SCs) that overexpress glial cell line-derived neurotrophic factor (GDNF). Unfortunately, constitutive GDNF overexpression in vivo can result in failure of regenerating axons to extend beyond the GDNF source, a phenomenon termed the “candy-store” effect. Little is known about the mechanism of this axon entrapment in vivo.
We present a reproducible in vitro culture platform using a microfluidic device to model axon entrapment and investigate mechanisms by which GDNF causes axon entrapment. The device is comprised of three culture chambers connected by two sets of microchannels, which prevent cell soma from moving between chambers but allow neurites to grow between chambers. Neurons from dorsal root ganglia were seeded in one end chamber while the effect of different conditions in the other two chambers was used to study neurite entrapment.
The results showed that GDNF-overexpressing SCs (G-SCs) can induce axon entrapment in vitro. We also found that while physiological levels of GDNF (100 ng/mL) promoted neurite extension, supra-physiological levels of GDNF (700 ng/mL) induced axon entrapment.
All previous work related to the “candy-store” effect were done in vivo. Here, we report the first in vitro platform that can recapitulate the axonal entrapment and investigate the mechanism of the phenomenon.
This platform facilitates investigation of the “candy-store” effect and shows the effects of high GDNF concentrations on neurite outgrowth. |
| doi_str_mv | 10.1016/j.jneumeth.2018.08.002 |
| format | Article |
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One potential treatment strategy to enhance axon regeneration is transplanting Schwann Cells (SCs) that overexpress glial cell line-derived neurotrophic factor (GDNF). Unfortunately, constitutive GDNF overexpression in vivo can result in failure of regenerating axons to extend beyond the GDNF source, a phenomenon termed the “candy-store” effect. Little is known about the mechanism of this axon entrapment in vivo.
We present a reproducible in vitro culture platform using a microfluidic device to model axon entrapment and investigate mechanisms by which GDNF causes axon entrapment. The device is comprised of three culture chambers connected by two sets of microchannels, which prevent cell soma from moving between chambers but allow neurites to grow between chambers. Neurons from dorsal root ganglia were seeded in one end chamber while the effect of different conditions in the other two chambers was used to study neurite entrapment.
The results showed that GDNF-overexpressing SCs (G-SCs) can induce axon entrapment in vitro. We also found that while physiological levels of GDNF (100 ng/mL) promoted neurite extension, supra-physiological levels of GDNF (700 ng/mL) induced axon entrapment.
All previous work related to the “candy-store” effect were done in vivo. Here, we report the first in vitro platform that can recapitulate the axonal entrapment and investigate the mechanism of the phenomenon.
This platform facilitates investigation of the “candy-store” effect and shows the effects of high GDNF concentrations on neurite outgrowth.</description><identifier>ISSN: 0165-0270</identifier><identifier>EISSN: 1872-678X</identifier><identifier>DOI: 10.1016/j.jneumeth.2018.08.002</identifier><identifier>PMID: 30081039</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Axon Guidance ; Axons - drug effects ; Axons - physiology ; Cell Culture Techniques - instrumentation ; Cell Culture Techniques - methods ; Chickens ; Ganglia, Spinal - drug effects ; Ganglia, Spinal - physiology ; Gene therapy ; Glial Cell Line-Derived Neurotrophic Factor - administration & dosage ; Glial Cell Line-Derived Neurotrophic Factor - physiology ; Lab-On-A-Chip Devices ; Male ; Microfluidic Analytical Techniques - instrumentation ; Microfluidic Analytical Techniques - methods ; Neurite extension ; Peripheral nerve injury ; Rats, Inbred Lew ; Schwann cells ; Schwann Cells - drug effects ; Schwann Cells - physiology ; Sensory Receptor Cells - drug effects ; Sensory Receptor Cells - physiology</subject><ispartof>Journal of neuroscience methods, 2018-10, Vol.308, p.183-191</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-2e036812d44f4c7bb58f514dd8c4134c04ed3ed017e3a33d747042181268fdcc3</citedby><cites>FETCH-LOGICAL-c471t-2e036812d44f4c7bb58f514dd8c4134c04ed3ed017e3a33d747042181268fdcc3</cites><orcidid>0000-0003-4832-5851</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0165027018302383$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30081039$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Ze Zhong</creatorcontrib><creatorcontrib>Wood, Matthew D.</creatorcontrib><creatorcontrib>Mackinnon, Susan E.</creatorcontrib><creatorcontrib>Sakiyama-Elbert, Shelly E.</creatorcontrib><title>A microfluidic platform to study the effects of GDNF on neuronal axon entrapment</title><title>Journal of neuroscience methods</title><addtitle>J Neurosci Methods</addtitle><description>•Microfluidic device recapitulates the axon entrapment in the “candy-store” effect.•GDNF-overexpressing SCs induce axon entrapment in the device as seen in vivo.•High concentration of GDNF is sufficient to induce axon entrapment.
One potential treatment strategy to enhance axon regeneration is transplanting Schwann Cells (SCs) that overexpress glial cell line-derived neurotrophic factor (GDNF). Unfortunately, constitutive GDNF overexpression in vivo can result in failure of regenerating axons to extend beyond the GDNF source, a phenomenon termed the “candy-store” effect. Little is known about the mechanism of this axon entrapment in vivo.
We present a reproducible in vitro culture platform using a microfluidic device to model axon entrapment and investigate mechanisms by which GDNF causes axon entrapment. The device is comprised of three culture chambers connected by two sets of microchannels, which prevent cell soma from moving between chambers but allow neurites to grow between chambers. Neurons from dorsal root ganglia were seeded in one end chamber while the effect of different conditions in the other two chambers was used to study neurite entrapment.
The results showed that GDNF-overexpressing SCs (G-SCs) can induce axon entrapment in vitro. We also found that while physiological levels of GDNF (100 ng/mL) promoted neurite extension, supra-physiological levels of GDNF (700 ng/mL) induced axon entrapment.
All previous work related to the “candy-store” effect were done in vivo. Here, we report the first in vitro platform that can recapitulate the axonal entrapment and investigate the mechanism of the phenomenon.
This platform facilitates investigation of the “candy-store” effect and shows the effects of high GDNF concentrations on neurite outgrowth.</description><subject>Animals</subject><subject>Axon Guidance</subject><subject>Axons - drug effects</subject><subject>Axons - physiology</subject><subject>Cell Culture Techniques - instrumentation</subject><subject>Cell Culture Techniques - methods</subject><subject>Chickens</subject><subject>Ganglia, Spinal - drug effects</subject><subject>Ganglia, Spinal - physiology</subject><subject>Gene therapy</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - administration & dosage</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - physiology</subject><subject>Lab-On-A-Chip Devices</subject><subject>Male</subject><subject>Microfluidic Analytical Techniques - instrumentation</subject><subject>Microfluidic Analytical Techniques - methods</subject><subject>Neurite extension</subject><subject>Peripheral nerve injury</subject><subject>Rats, Inbred Lew</subject><subject>Schwann cells</subject><subject>Schwann Cells - drug effects</subject><subject>Schwann Cells - physiology</subject><subject>Sensory Receptor Cells - drug effects</subject><subject>Sensory Receptor Cells - physiology</subject><issn>0165-0270</issn><issn>1872-678X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUV1rFDEUDaLYbfUvlDz6MuvNx2ayL2JpbSsU9UHBt5BNbtwsM5M1yRT7703dtuiTcOEScj4u5xByymDJgKm3u-VuwnnEul1yYHoJbYA_Iwume96pXn9_ThYNuOqA93BEjkvZAYBcg3pJjgSAZiDWC_LljI7R5RSGOfro6H6wNaQ80ppoqbO_o3WLFENAVwtNgV5dfLqkaaLNPafJDtT-ai-carb7sa1X5EWwQ8HXD_uEfLv88PX8urv5fPXx_Oymc7JnteMIQmnGvZRBun6zWemwYtJ77SQT0oFEL9AD61FYIXwve5CcNYbSwTsnTsi7g-5-3ozo3Z8LBrPPcbT5ziQbzb8_U9yaH-nWKA6ghGgCbx4Ecvo5Y6lmjMXhMNgJ01wMBy3XQjGlG1QdoC2oUjKGJxsG5r4OszOPdZj7Ogy0Ad6Ip38f-UR7zL8B3h8A2KK6jZhNcREnhz7mlrjxKf7P4zcHh6BW</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Wang, Ze Zhong</creator><creator>Wood, Matthew D.</creator><creator>Mackinnon, Susan E.</creator><creator>Sakiyama-Elbert, Shelly E.</creator><general>Elsevier B.V</general><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><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4832-5851</orcidid></search><sort><creationdate>20181001</creationdate><title>A microfluidic platform to study the effects of GDNF on neuronal axon entrapment</title><author>Wang, Ze Zhong ; Wood, Matthew D. ; Mackinnon, Susan E. ; Sakiyama-Elbert, Shelly E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-2e036812d44f4c7bb58f514dd8c4134c04ed3ed017e3a33d747042181268fdcc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Axon Guidance</topic><topic>Axons - drug effects</topic><topic>Axons - physiology</topic><topic>Cell Culture Techniques - instrumentation</topic><topic>Cell Culture Techniques - methods</topic><topic>Chickens</topic><topic>Ganglia, Spinal - drug effects</topic><topic>Ganglia, Spinal - physiology</topic><topic>Gene therapy</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - administration & dosage</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - physiology</topic><topic>Lab-On-A-Chip Devices</topic><topic>Male</topic><topic>Microfluidic Analytical Techniques - instrumentation</topic><topic>Microfluidic Analytical Techniques - methods</topic><topic>Neurite extension</topic><topic>Peripheral nerve injury</topic><topic>Rats, Inbred Lew</topic><topic>Schwann cells</topic><topic>Schwann Cells - drug effects</topic><topic>Schwann Cells - physiology</topic><topic>Sensory Receptor Cells - drug effects</topic><topic>Sensory Receptor Cells - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Ze Zhong</creatorcontrib><creatorcontrib>Wood, Matthew D.</creatorcontrib><creatorcontrib>Mackinnon, Susan E.</creatorcontrib><creatorcontrib>Sakiyama-Elbert, Shelly E.</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neuroscience methods</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Ze Zhong</au><au>Wood, Matthew D.</au><au>Mackinnon, Susan E.</au><au>Sakiyama-Elbert, Shelly E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A microfluidic platform to study the effects of GDNF on neuronal axon entrapment</atitle><jtitle>Journal of neuroscience methods</jtitle><addtitle>J Neurosci Methods</addtitle><date>2018-10-01</date><risdate>2018</risdate><volume>308</volume><spage>183</spage><epage>191</epage><pages>183-191</pages><issn>0165-0270</issn><eissn>1872-678X</eissn><abstract>•Microfluidic device recapitulates the axon entrapment in the “candy-store” effect.•GDNF-overexpressing SCs induce axon entrapment in the device as seen in vivo.•High concentration of GDNF is sufficient to induce axon entrapment.
One potential treatment strategy to enhance axon regeneration is transplanting Schwann Cells (SCs) that overexpress glial cell line-derived neurotrophic factor (GDNF). Unfortunately, constitutive GDNF overexpression in vivo can result in failure of regenerating axons to extend beyond the GDNF source, a phenomenon termed the “candy-store” effect. Little is known about the mechanism of this axon entrapment in vivo.
We present a reproducible in vitro culture platform using a microfluidic device to model axon entrapment and investigate mechanisms by which GDNF causes axon entrapment. The device is comprised of three culture chambers connected by two sets of microchannels, which prevent cell soma from moving between chambers but allow neurites to grow between chambers. Neurons from dorsal root ganglia were seeded in one end chamber while the effect of different conditions in the other two chambers was used to study neurite entrapment.
The results showed that GDNF-overexpressing SCs (G-SCs) can induce axon entrapment in vitro. We also found that while physiological levels of GDNF (100 ng/mL) promoted neurite extension, supra-physiological levels of GDNF (700 ng/mL) induced axon entrapment.
All previous work related to the “candy-store” effect were done in vivo. Here, we report the first in vitro platform that can recapitulate the axonal entrapment and investigate the mechanism of the phenomenon.
This platform facilitates investigation of the “candy-store” effect and shows the effects of high GDNF concentrations on neurite outgrowth.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30081039</pmid><doi>10.1016/j.jneumeth.2018.08.002</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-4832-5851</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of neuroscience methods, 2018-10, Vol.308, p.183-191 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Axon Guidance Axons - drug effects Axons - physiology Cell Culture Techniques - instrumentation Cell Culture Techniques - methods Chickens Ganglia, Spinal - drug effects Ganglia, Spinal - physiology Gene therapy Glial Cell Line-Derived Neurotrophic Factor - administration & dosage Glial Cell Line-Derived Neurotrophic Factor - physiology Lab-On-A-Chip Devices Male Microfluidic Analytical Techniques - instrumentation Microfluidic Analytical Techniques - methods Neurite extension Peripheral nerve injury Rats, Inbred Lew Schwann cells Schwann Cells - drug effects Schwann Cells - physiology Sensory Receptor Cells - drug effects Sensory Receptor Cells - physiology |
| title | A microfluidic platform to study the effects of GDNF on neuronal axon entrapment |
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