MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice
Dry eye disease (DED) is a multifactorial disease characterized by a disrupted tear film homeostasis and inflammation leading to visual impairments and pain in patients. Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (...
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| Veröffentlicht in: | Scientific reports 2019-12, Vol.9 (1), p.18299-14, Article 18299 |
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| description | Dry eye disease (DED) is a multifactorial disease characterized by a disrupted tear film homeostasis and inflammation leading to visual impairments and pain in patients. Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (LG) tissue. Despite a high prevalence, therapies remain palliative. Therefore, it is of great interest to develop new approaches to curatively treat ADDE. Mesenchymal stem/stromal cells (MSC) have been shown to induce tissue regeneration and cease inflammation. Moreover, an increasing amount of MSC was found in the regenerating LG of mice. Therefore, this study investigated the therapeutic effect of MSC transplantation on damaged LGs using duct ligation induced ADDE in mice. Due to the transplantation of sex-mismatched and eGFP-expressing MSC, MSC could be identified and detected until day 21. MSC transplantation significantly improved LG regeneration, as the amount of vital acinar structures was significantly increased above the intrinsic regeneration capacity of control. Additionally, MSC transplantation modulated the immune reaction as macrophage infiltration was delayed and TNFα expression decreased, accompanied by an increased IL-6 expression. Thus, the application of MSC appears to be a promising therapeutic approach to induce LG regeneration in patients suffering from severe DED/ADDE. |
| doi_str_mv | 10.1038/s41598-019-54840-5 |
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Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (LG) tissue. Despite a high prevalence, therapies remain palliative. Therefore, it is of great interest to develop new approaches to curatively treat ADDE. Mesenchymal stem/stromal cells (MSC) have been shown to induce tissue regeneration and cease inflammation. Moreover, an increasing amount of MSC was found in the regenerating LG of mice. Therefore, this study investigated the therapeutic effect of MSC transplantation on damaged LGs using duct ligation induced ADDE in mice. Due to the transplantation of sex-mismatched and eGFP-expressing MSC, MSC could be identified and detected until day 21. MSC transplantation significantly improved LG regeneration, as the amount of vital acinar structures was significantly increased above the intrinsic regeneration capacity of control. Additionally, MSC transplantation modulated the immune reaction as macrophage infiltration was delayed and TNFα expression decreased, accompanied by an increased IL-6 expression. 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Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (LG) tissue. Despite a high prevalence, therapies remain palliative. Therefore, it is of great interest to develop new approaches to curatively treat ADDE. Mesenchymal stem/stromal cells (MSC) have been shown to induce tissue regeneration and cease inflammation. Moreover, an increasing amount of MSC was found in the regenerating LG of mice. Therefore, this study investigated the therapeutic effect of MSC transplantation on damaged LGs using duct ligation induced ADDE in mice. Due to the transplantation of sex-mismatched and eGFP-expressing MSC, MSC could be identified and detected until day 21. MSC transplantation significantly improved LG regeneration, as the amount of vital acinar structures was significantly increased above the intrinsic regeneration capacity of control. Additionally, MSC transplantation modulated the immune reaction as macrophage infiltration was delayed and TNFα expression decreased, accompanied by an increased IL-6 expression. Thus, the application of MSC appears to be a promising therapeutic approach to induce LG regeneration in patients suffering from severe DED/ADDE.</description><subject>13/1</subject><subject>13/100</subject><subject>13/106</subject><subject>13/2</subject><subject>13/21</subject><subject>13/31</subject><subject>13/51</subject><subject>14/35</subject><subject>14/63</subject><subject>38/22</subject><subject>38/77</subject><subject>45/90</subject><subject>631/532/2118/2074</subject><subject>631/532/489</subject><subject>64/60</subject><subject>82/29</subject><subject>82/80</subject><subject>Animals</subject><subject>Dry Eye Syndromes - therapy</subject><subject>Eye</subject><subject>Eye diseases</subject><subject>Female</subject><subject>Homeostasis</subject><subject>Humanities and Social Sciences</subject><subject>Interleukin 6</subject><subject>Lacrimal Apparatus - pathology</subject><subject>Lacrimal Apparatus - physiology</subject><subject>Lacrimal gland and Nasolacrimal duct</subject><subject>Macrophages</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>multidisciplinary</subject><subject>Regeneration</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Stromal cells</subject><subject>Transplantation</subject><subject>Tumor necrosis factor-α</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kcFvFCEUxonR2Kb2H_BgSLx4GQUGBriYmG2tm2xjYuuZMPBYaWaZFWaa7H9f6tRaPcgFku_3vsd7H0KvKXlPSas-FE6FVg2huhFccdKIZ-iYES4a1jL2_Mn7CJ2WckPqEUxzql-io5ZKLZUWxyheXq3wdbap7AebJjvFMeH1bp_HWyh4Y12OOzvgiyp6_A22kCAvkA0TZHw15210dhgOeJ387MDjs3zA5wfAZ7GALYBjwpfRwSv0ItihwOnDfYK-fz6_Xn1pNl8v1qtPm8ZxyafGBamsdFwI30vCZU_boFXw3jLeewJWB-oc8E521End90EDsbL1rAuB-a49QR8X3_3c78A7SFO2g9nfD5IPZrTR_K2k-MNsx1vTKV33w6rBuweDPP6coUxmF4uDoa4AxrmYulPadYpxUtG3_6A345xTHW-hlBJEV4otlMtjKRnC42coMfdhmiVMU8M0v8I0oha9eTrGY8nv6CrQLkCpUtpC_tP7P7Z386OsDg</recordid><startdate>20191204</startdate><enddate>20191204</enddate><creator>Dietrich, Jana</creator><creator>Ott, Lolita</creator><creator>Roth, Mathias</creator><creator>Witt, Joana</creator><creator>Geerling, Gerd</creator><creator>Mertsch, Sonja</creator><creator>Schrader, Stefan</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7243-7493</orcidid><orcidid>https://orcid.org/0000-0001-7211-3168</orcidid><orcidid>https://orcid.org/0000-0001-8803-9150</orcidid></search><sort><creationdate>20191204</creationdate><title>MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice</title><author>Dietrich, Jana ; Ott, Lolita ; Roth, Mathias ; Witt, Joana ; Geerling, Gerd ; Mertsch, Sonja ; Schrader, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-cf78a7c455db7047b13f98fdda24bd0ea9f1cce46761c79bbf9e0a73d26ff2d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/1</topic><topic>13/100</topic><topic>13/106</topic><topic>13/2</topic><topic>13/21</topic><topic>13/31</topic><topic>13/51</topic><topic>14/35</topic><topic>14/63</topic><topic>38/22</topic><topic>38/77</topic><topic>45/90</topic><topic>631/532/2118/2074</topic><topic>631/532/489</topic><topic>64/60</topic><topic>82/29</topic><topic>82/80</topic><topic>Animals</topic><topic>Dry Eye Syndromes - therapy</topic><topic>Eye</topic><topic>Eye diseases</topic><topic>Female</topic><topic>Homeostasis</topic><topic>Humanities and Social Sciences</topic><topic>Interleukin 6</topic><topic>Lacrimal Apparatus - pathology</topic><topic>Lacrimal Apparatus - physiology</topic><topic>Lacrimal gland and Nasolacrimal duct</topic><topic>Macrophages</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>multidisciplinary</topic><topic>Regeneration</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Stromal cells</topic><topic>Transplantation</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dietrich, Jana</creatorcontrib><creatorcontrib>Ott, Lolita</creatorcontrib><creatorcontrib>Roth, Mathias</creatorcontrib><creatorcontrib>Witt, Joana</creatorcontrib><creatorcontrib>Geerling, Gerd</creatorcontrib><creatorcontrib>Mertsch, Sonja</creatorcontrib><creatorcontrib>Schrader, Stefan</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dietrich, Jana</au><au>Ott, Lolita</au><au>Roth, Mathias</au><au>Witt, Joana</au><au>Geerling, Gerd</au><au>Mertsch, Sonja</au><au>Schrader, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-12-04</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>18299</spage><epage>14</epage><pages>18299-14</pages><artnum>18299</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Dry eye disease (DED) is a multifactorial disease characterized by a disrupted tear film homeostasis and inflammation leading to visual impairments and pain in patients. Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (LG) tissue. Despite a high prevalence, therapies remain palliative. Therefore, it is of great interest to develop new approaches to curatively treat ADDE. Mesenchymal stem/stromal cells (MSC) have been shown to induce tissue regeneration and cease inflammation. Moreover, an increasing amount of MSC was found in the regenerating LG of mice. Therefore, this study investigated the therapeutic effect of MSC transplantation on damaged LGs using duct ligation induced ADDE in mice. Due to the transplantation of sex-mismatched and eGFP-expressing MSC, MSC could be identified and detected until day 21. MSC transplantation significantly improved LG regeneration, as the amount of vital acinar structures was significantly increased above the intrinsic regeneration capacity of control. Additionally, MSC transplantation modulated the immune reaction as macrophage infiltration was delayed and TNFα expression decreased, accompanied by an increased IL-6 expression. Thus, the application of MSC appears to be a promising therapeutic approach to induce LG regeneration in patients suffering from severe DED/ADDE.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31797895</pmid><doi>10.1038/s41598-019-54840-5</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-7243-7493</orcidid><orcidid>https://orcid.org/0000-0001-7211-3168</orcidid><orcidid>https://orcid.org/0000-0001-8803-9150</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/1 13/100 13/106 13/2 13/21 13/31 13/51 14/35 14/63 38/22 38/77 45/90 631/532/2118/2074 631/532/489 64/60 82/29 82/80 Animals Dry Eye Syndromes - therapy Eye Eye diseases Female Homeostasis Humanities and Social Sciences Interleukin 6 Lacrimal Apparatus - pathology Lacrimal Apparatus - physiology Lacrimal gland and Nasolacrimal duct Macrophages Male Mesenchymal Stem Cell Transplantation Mesenchyme Mice Mice, Inbred C57BL multidisciplinary Regeneration Science Science (multidisciplinary) Stromal cells Transplantation Tumor necrosis factor-α |
| title | MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice |
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