Establishment of a novel in vitro co-culture system of enteric neurons and Caco-2 cells for evaluating the effect of enteric nervous system on transepithelial transport of drugs
[Display omitted] •Isolated NCS-like cells from LMMP were proliferated and differentiated into neurons.•Establishment of a novel co-culture system of Caco-2 cells and enteric neurons.•Enteric neurons mainly affected the passive transport via paracellular pathway. The gastrointestinal tract is innerv...
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| Veröffentlicht in: | International journal of pharmaceutics 2023-02, Vol.633, p.122617-122617, Article 122617 |
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| container_title | International journal of pharmaceutics |
| container_volume | 633 |
| creator | Maruyama, Masato Yoshikata, Minami Sakaguchi, Mana Wakushima, Shizuka Higaki, Kazutaka |
| description | [Display omitted]
•Isolated NCS-like cells from LMMP were proliferated and differentiated into neurons.•Establishment of a novel co-culture system of Caco-2 cells and enteric neurons.•Enteric neurons mainly affected the passive transport via paracellular pathway.
The gastrointestinal tract is innervated by extrinsic autonomic nerves and intrinsic enteric nervous system (ENS). However, the role of ENS in drug absorption has remained to be clarified. To investigate the effect of ENS on drug transport across the intestinal epithelial cells, we established a novel co-culture system of Caco-2 cells and enteric neurons differentiated from neural crest stem (NCS)-like cells isolated from mouse longitudinal muscle/myenteric plexus (LMMP). Immunostaining analysis revealed that the proportions of neuron, glia, and NCS-like cells were only |
| doi_str_mv | 10.1016/j.ijpharm.2023.122617 |
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•Isolated NCS-like cells from LMMP were proliferated and differentiated into neurons.•Establishment of a novel co-culture system of Caco-2 cells and enteric neurons.•Enteric neurons mainly affected the passive transport via paracellular pathway.
The gastrointestinal tract is innervated by extrinsic autonomic nerves and intrinsic enteric nervous system (ENS). However, the role of ENS in drug absorption has remained to be clarified. To investigate the effect of ENS on drug transport across the intestinal epithelial cells, we established a novel co-culture system of Caco-2 cells and enteric neurons differentiated from neural crest stem (NCS)-like cells isolated from mouse longitudinal muscle/myenteric plexus (LMMP). Immunostaining analysis revealed that the proportions of neuron, glia, and NCS-like cells were only <5 % at population in the primary culture of LMMP cells. Therefore, we proliferated NCS-like cells and differentiated them into neuronal cells and successfully increased the neuronal cell population upto about 40 %. Then, the differentiated neuronal cells were co-cultured with Caco-2 cell monolayers, and we found that the co-culture significantly decreased the transepithelial electrical resistance and enhanced the transport of fluorescein isothiocyanate-labeled dextran-4 across Caco-2 cell monolayers, suggesting that the enteric neurons would function to open the tight junction and facilitate the drug transport via the paracellular route. On the other hand, no changes in the permeability of antipyrine were observed, suggesting that the enteric neurons would not affect the passive transport via the transcellular pathway.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2023.122617</identifier><identifier>PMID: 36657552</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Caco-2 Cells ; Coculture Techniques ; Drug transport ; Enteric nervous system ; Enteric Nervous System - physiology ; Humans ; Intestinal epithelial cells ; Intestine, Small - metabolism ; Mice ; Neural crest stem cells ; Neurons - metabolism ; Tight junction</subject><ispartof>International journal of pharmaceutics, 2023-02, Vol.633, p.122617-122617, Article 122617</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-d02032c57c0f21e15eb7b409b8ee48f4fc47bce4496f2b6ca6c3ff56534272d63</citedby><cites>FETCH-LOGICAL-c431t-d02032c57c0f21e15eb7b409b8ee48f4fc47bce4496f2b6ca6c3ff56534272d63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378517323000376$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36657552$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maruyama, Masato</creatorcontrib><creatorcontrib>Yoshikata, Minami</creatorcontrib><creatorcontrib>Sakaguchi, Mana</creatorcontrib><creatorcontrib>Wakushima, Shizuka</creatorcontrib><creatorcontrib>Higaki, Kazutaka</creatorcontrib><title>Establishment of a novel in vitro co-culture system of enteric neurons and Caco-2 cells for evaluating the effect of enteric nervous system on transepithelial transport of drugs</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
•Isolated NCS-like cells from LMMP were proliferated and differentiated into neurons.•Establishment of a novel co-culture system of Caco-2 cells and enteric neurons.•Enteric neurons mainly affected the passive transport via paracellular pathway.
The gastrointestinal tract is innervated by extrinsic autonomic nerves and intrinsic enteric nervous system (ENS). However, the role of ENS in drug absorption has remained to be clarified. To investigate the effect of ENS on drug transport across the intestinal epithelial cells, we established a novel co-culture system of Caco-2 cells and enteric neurons differentiated from neural crest stem (NCS)-like cells isolated from mouse longitudinal muscle/myenteric plexus (LMMP). Immunostaining analysis revealed that the proportions of neuron, glia, and NCS-like cells were only <5 % at population in the primary culture of LMMP cells. Therefore, we proliferated NCS-like cells and differentiated them into neuronal cells and successfully increased the neuronal cell population upto about 40 %. Then, the differentiated neuronal cells were co-cultured with Caco-2 cell monolayers, and we found that the co-culture significantly decreased the transepithelial electrical resistance and enhanced the transport of fluorescein isothiocyanate-labeled dextran-4 across Caco-2 cell monolayers, suggesting that the enteric neurons would function to open the tight junction and facilitate the drug transport via the paracellular route. On the other hand, no changes in the permeability of antipyrine were observed, suggesting that the enteric neurons would not affect the passive transport via the transcellular pathway.</description><subject>Animals</subject><subject>Caco-2 Cells</subject><subject>Coculture Techniques</subject><subject>Drug transport</subject><subject>Enteric nervous system</subject><subject>Enteric Nervous System - physiology</subject><subject>Humans</subject><subject>Intestinal epithelial cells</subject><subject>Intestine, Small - metabolism</subject><subject>Mice</subject><subject>Neural crest stem cells</subject><subject>Neurons - metabolism</subject><subject>Tight junction</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUhi0EokPhEUBessngS2ynK4RG5SJVYgNry3GOOx45drCdSH0s3rAZMlRixerI0vefiz-E3lKyp4TKD6e9P01Hk8c9I4zvKWOSqmdoRzvFG94q-RztCFddI6jiV-hVKSdCiGSUv0RXXEqhhGA79Pu2VNMHX44jxIqTwwbHtEDAPuLF15ywTY2dQ50z4PJQKoxnaoUhe4sjzDnFgk0c8MGsKMMWQijYpYxhMWE21cd7XI-AwTmw9d90XtJcnvpGXLOJBSa_8sGbsL2nlP_Ehjzfl9fohTOhwJtLvUY_P9_-OHxt7r5_-Xb4dNfYltPaDIQRzqxQljhGgQroVd-Sm74DaDvXOtuq3kLb3kjHemmNtNw5IQVvmWKD5Nfo_dZ3yunXDKXq0ZfzbSbCurNmSnaMqU6JFRUbanMqJYPTU_ajyQ-aEn22pU_6YkufbenN1pp7dxkx9yMMT6m_elbg4wbAeujiIetiPUQLg8_rV-oh-f-MeATbg60J</recordid><startdate>20230225</startdate><enddate>20230225</enddate><creator>Maruyama, Masato</creator><creator>Yoshikata, Minami</creator><creator>Sakaguchi, Mana</creator><creator>Wakushima, Shizuka</creator><creator>Higaki, Kazutaka</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></search><sort><creationdate>20230225</creationdate><title>Establishment of a novel in vitro co-culture system of enteric neurons and Caco-2 cells for evaluating the effect of enteric nervous system on transepithelial transport of drugs</title><author>Maruyama, Masato ; Yoshikata, Minami ; Sakaguchi, Mana ; Wakushima, Shizuka ; Higaki, Kazutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-d02032c57c0f21e15eb7b409b8ee48f4fc47bce4496f2b6ca6c3ff56534272d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Caco-2 Cells</topic><topic>Coculture Techniques</topic><topic>Drug transport</topic><topic>Enteric nervous system</topic><topic>Enteric Nervous System - physiology</topic><topic>Humans</topic><topic>Intestinal epithelial cells</topic><topic>Intestine, Small - metabolism</topic><topic>Mice</topic><topic>Neural crest stem cells</topic><topic>Neurons - metabolism</topic><topic>Tight junction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maruyama, Masato</creatorcontrib><creatorcontrib>Yoshikata, Minami</creatorcontrib><creatorcontrib>Sakaguchi, Mana</creatorcontrib><creatorcontrib>Wakushima, Shizuka</creatorcontrib><creatorcontrib>Higaki, Kazutaka</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><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maruyama, Masato</au><au>Yoshikata, Minami</au><au>Sakaguchi, Mana</au><au>Wakushima, Shizuka</au><au>Higaki, Kazutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Establishment of a novel in vitro co-culture system of enteric neurons and Caco-2 cells for evaluating the effect of enteric nervous system on transepithelial transport of drugs</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2023-02-25</date><risdate>2023</risdate><volume>633</volume><spage>122617</spage><epage>122617</epage><pages>122617-122617</pages><artnum>122617</artnum><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
•Isolated NCS-like cells from LMMP were proliferated and differentiated into neurons.•Establishment of a novel co-culture system of Caco-2 cells and enteric neurons.•Enteric neurons mainly affected the passive transport via paracellular pathway.
The gastrointestinal tract is innervated by extrinsic autonomic nerves and intrinsic enteric nervous system (ENS). However, the role of ENS in drug absorption has remained to be clarified. To investigate the effect of ENS on drug transport across the intestinal epithelial cells, we established a novel co-culture system of Caco-2 cells and enteric neurons differentiated from neural crest stem (NCS)-like cells isolated from mouse longitudinal muscle/myenteric plexus (LMMP). Immunostaining analysis revealed that the proportions of neuron, glia, and NCS-like cells were only <5 % at population in the primary culture of LMMP cells. Therefore, we proliferated NCS-like cells and differentiated them into neuronal cells and successfully increased the neuronal cell population upto about 40 %. Then, the differentiated neuronal cells were co-cultured with Caco-2 cell monolayers, and we found that the co-culture significantly decreased the transepithelial electrical resistance and enhanced the transport of fluorescein isothiocyanate-labeled dextran-4 across Caco-2 cell monolayers, suggesting that the enteric neurons would function to open the tight junction and facilitate the drug transport via the paracellular route. On the other hand, no changes in the permeability of antipyrine were observed, suggesting that the enteric neurons would not affect the passive transport via the transcellular pathway.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>36657552</pmid><doi>10.1016/j.ijpharm.2023.122617</doi><tpages>1</tpages></addata></record> |
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| subjects | Animals Caco-2 Cells Coculture Techniques Drug transport Enteric nervous system Enteric Nervous System - physiology Humans Intestinal epithelial cells Intestine, Small - metabolism Mice Neural crest stem cells Neurons - metabolism Tight junction |
| title | Establishment of a novel in vitro co-culture system of enteric neurons and Caco-2 cells for evaluating the effect of enteric nervous system on transepithelial transport of drugs |
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