Proteomic profiling of striatal tissue of a rat model of Parkinson's disease after implantation of collagen‐encapsulated human umbilical cord mesenchymal stem cells
Parkinson's disease (PD) is the most common neurodegenerative disorder of movement worldwide. To date, only symptomatic treatments are available. Implantation of collagen‐encapsulated human umbilical cord mesenchymal stem cells (hUC‐MSCs) is being developed as a novel therapeutic approach to po...
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Veröffentlicht in: | Journal of tissue engineering and regenerative medicine 2020-08, Vol.14 (8), p.1077-1086 |
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creator | Santaella, Anna Wessels, Hans J.C.T. Kulkarni, Purva Gloerich, Jolein Kuiperij, Bea Bloem, Bastiaan R. Gool, Alain J. Cabré, Silvia Alamilla, Verónica Verbeek, Marcel M. |
description | Parkinson's disease (PD) is the most common neurodegenerative disorder of movement worldwide. To date, only symptomatic treatments are available. Implantation of collagen‐encapsulated human umbilical cord mesenchymal stem cells (hUC‐MSCs) is being developed as a novel therapeutic approach to potentially modify PD progression. However, implanted collagen scaffolds may induce a host tissue response. To gain insight into such response, hUC‐MSCs were encapsulated into collagen hydrogels and implanted into the striatum of hemi‐Parkinsonian male Sprague–Dawley rats. One or 14 days after implantation, the area of interest was dissected using a cryostat. Total protein extracts were subjected to tryptic digestion and subsequent LC–MS/MS analyses for protein expression profiling. Univariate and multivariate analyses were performed to identify differentially expressed protein profiles with subsequent gene ontology and pathway analysis for biological interpretation of the data; 2,219 proteins were identified by MaxQuant at 1% false discovery rate. A high correlation of label‐free quantification (LFQ) protein values between biological replicates (r = .95) was observed. No significant differences were observed between brains treated with encapsulated hUC‐MSCs compared to appropriate controls. Proteomic data were highly robust and reproducible, indicating the suitability of this approach to map differential protein expression caused by the implants. The lack of differences between conditions suggests that the effects of implantation may be minimal. Alternatively, effects may only have been focal and/or could have been masked by nonrelevant high‐abundant proteins. For follow‐up assessment of local changes, a more accurate dissection technique, such as laser micro dissection, and analysis method are recommended. |
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To date, only symptomatic treatments are available. Implantation of collagen‐encapsulated human umbilical cord mesenchymal stem cells (hUC‐MSCs) is being developed as a novel therapeutic approach to potentially modify PD progression. However, implanted collagen scaffolds may induce a host tissue response. To gain insight into such response, hUC‐MSCs were encapsulated into collagen hydrogels and implanted into the striatum of hemi‐Parkinsonian male Sprague–Dawley rats. One or 14 days after implantation, the area of interest was dissected using a cryostat. Total protein extracts were subjected to tryptic digestion and subsequent LC–MS/MS analyses for protein expression profiling. Univariate and multivariate analyses were performed to identify differentially expressed protein profiles with subsequent gene ontology and pathway analysis for biological interpretation of the data; 2,219 proteins were identified by MaxQuant at 1% false discovery rate. A high correlation of label‐free quantification (LFQ) protein values between biological replicates (r = .95) was observed. No significant differences were observed between brains treated with encapsulated hUC‐MSCs compared to appropriate controls. Proteomic data were highly robust and reproducible, indicating the suitability of this approach to map differential protein expression caused by the implants. The lack of differences between conditions suggests that the effects of implantation may be minimal. Alternatively, effects may only have been focal and/or could have been masked by nonrelevant high‐abundant proteins. For follow‐up assessment of local changes, a more accurate dissection technique, such as laser micro dissection, and analysis method are recommended.</description><identifier>ISSN: 1932-6254</identifier><identifier>EISSN: 1932-7005</identifier><identifier>DOI: 10.1002/term.3081</identifier><identifier>PMID: 32548924</identifier><language>eng</language><publisher>Hoboken: Hindawi Limited</publisher><subject>Basal ganglia ; Central nervous system diseases ; Collagen ; collagen hydrogels ; Dissection ; Encapsulation ; Hydrogels ; Implantation ; Medical treatment ; Mesenchymal stem cells ; Movement disorders ; Neostriatum ; Neurodegenerative diseases ; Parkinson's disease ; Protein expression ; Proteins ; proteomics ; rat model ; Regenerative medicine ; Stem cell transplantation ; Stem cells ; Tissue engineering ; Umbilical cord</subject><ispartof>Journal of tissue engineering and regenerative medicine, 2020-08, Vol.14 (8), p.1077-1086</ispartof><rights>2020 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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To date, only symptomatic treatments are available. Implantation of collagen‐encapsulated human umbilical cord mesenchymal stem cells (hUC‐MSCs) is being developed as a novel therapeutic approach to potentially modify PD progression. However, implanted collagen scaffolds may induce a host tissue response. To gain insight into such response, hUC‐MSCs were encapsulated into collagen hydrogels and implanted into the striatum of hemi‐Parkinsonian male Sprague–Dawley rats. One or 14 days after implantation, the area of interest was dissected using a cryostat. Total protein extracts were subjected to tryptic digestion and subsequent LC–MS/MS analyses for protein expression profiling. Univariate and multivariate analyses were performed to identify differentially expressed protein profiles with subsequent gene ontology and pathway analysis for biological interpretation of the data; 2,219 proteins were identified by MaxQuant at 1% false discovery rate. A high correlation of label‐free quantification (LFQ) protein values between biological replicates (r = .95) was observed. No significant differences were observed between brains treated with encapsulated hUC‐MSCs compared to appropriate controls. Proteomic data were highly robust and reproducible, indicating the suitability of this approach to map differential protein expression caused by the implants. The lack of differences between conditions suggests that the effects of implantation may be minimal. Alternatively, effects may only have been focal and/or could have been masked by nonrelevant high‐abundant proteins. For follow‐up assessment of local changes, a more accurate dissection technique, such as laser micro dissection, and analysis method are recommended.</description><subject>Basal ganglia</subject><subject>Central nervous system diseases</subject><subject>Collagen</subject><subject>collagen hydrogels</subject><subject>Dissection</subject><subject>Encapsulation</subject><subject>Hydrogels</subject><subject>Implantation</subject><subject>Medical treatment</subject><subject>Mesenchymal stem cells</subject><subject>Movement disorders</subject><subject>Neostriatum</subject><subject>Neurodegenerative diseases</subject><subject>Parkinson's disease</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>proteomics</subject><subject>rat model</subject><subject>Regenerative medicine</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Tissue engineering</subject><subject>Umbilical cord</subject><issn>1932-6254</issn><issn>1932-7005</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp1kU1uFDEQhVsIREJgwQ0ssQAWk9ht9483SChKACmICIW1VeOunnHwT2O7QbPLETgFB-MkuJkREkisbL_6_KpKr6qeMnrKKK3PMkZ3ymnP7lXHTPJ61VHa3D_c27oRR9WjlG6L2LQNf1gd8aL1shbH1Y_rGDIGZzSZYhiNNX5DwkhSjgYyWJJNSjMuEpAImbgwoF2e1xA_G5-Cf57IYBJCQgJjGYUYN1nwGbIJfiF1sBY26H_efUevYUqzhYwD2c4OPJndunTVpZUOcSAOU4G2O1eElNERjdamx9WDEWzCJ4fzpPp0eXFz_nZ19eHNu_PXVystaspWHYd6PWpG66FrAGTdo5Sd5nWLEgWXg5TrYegEyk5qylqOoMWoBeOs6cZe85Pq1d53mtcOB40-R7BqisZB3KkARv1d8WarNuGr6oRsGefF4MXBIIYvM6asnEnLCuAxzEnVggnBSjB9QZ_9g96GOfqyXqE4p8tQTaFe7ikdQ0oRxz_DMKqW9NWSvlrSL-zZnv1mLO7-D6qbi4_vf__4BfwQtc8</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Santaella, Anna</creator><creator>Wessels, Hans J.C.T.</creator><creator>Kulkarni, Purva</creator><creator>Gloerich, Jolein</creator><creator>Kuiperij, Bea</creator><creator>Bloem, Bastiaan R.</creator><creator>Gool, Alain J.</creator><creator>Cabré, Silvia</creator><creator>Alamilla, Verónica</creator><creator>Verbeek, Marcel M.</creator><general>Hindawi Limited</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3630-0094</orcidid></search><sort><creationdate>202008</creationdate><title>Proteomic profiling of striatal tissue of a rat model of Parkinson's disease after implantation of collagen‐encapsulated human umbilical cord mesenchymal stem cells</title><author>Santaella, Anna ; Wessels, Hans J.C.T. ; Kulkarni, Purva ; Gloerich, Jolein ; Kuiperij, Bea ; Bloem, Bastiaan R. ; Gool, Alain J. ; Cabré, Silvia ; Alamilla, Verónica ; Verbeek, Marcel M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4201-73a2bfc102d75aa928e997c326e9e439d99bdd74e979c0163eac4fc413157f8c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Basal ganglia</topic><topic>Central nervous system diseases</topic><topic>Collagen</topic><topic>collagen hydrogels</topic><topic>Dissection</topic><topic>Encapsulation</topic><topic>Hydrogels</topic><topic>Implantation</topic><topic>Medical treatment</topic><topic>Mesenchymal stem cells</topic><topic>Movement disorders</topic><topic>Neostriatum</topic><topic>Neurodegenerative diseases</topic><topic>Parkinson's disease</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>proteomics</topic><topic>rat model</topic><topic>Regenerative medicine</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tissue engineering</topic><topic>Umbilical cord</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Santaella, Anna</creatorcontrib><creatorcontrib>Wessels, Hans J.C.T.</creatorcontrib><creatorcontrib>Kulkarni, Purva</creatorcontrib><creatorcontrib>Gloerich, Jolein</creatorcontrib><creatorcontrib>Kuiperij, Bea</creatorcontrib><creatorcontrib>Bloem, Bastiaan R.</creatorcontrib><creatorcontrib>Gool, Alain J.</creatorcontrib><creatorcontrib>Cabré, Silvia</creatorcontrib><creatorcontrib>Alamilla, Verónica</creatorcontrib><creatorcontrib>Verbeek, Marcel M.</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of tissue engineering and regenerative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Santaella, Anna</au><au>Wessels, Hans J.C.T.</au><au>Kulkarni, Purva</au><au>Gloerich, Jolein</au><au>Kuiperij, Bea</au><au>Bloem, Bastiaan R.</au><au>Gool, Alain J.</au><au>Cabré, Silvia</au><au>Alamilla, Verónica</au><au>Verbeek, Marcel M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteomic profiling of striatal tissue of a rat model of Parkinson's disease after implantation of collagen‐encapsulated human umbilical cord mesenchymal stem cells</atitle><jtitle>Journal of tissue engineering and regenerative medicine</jtitle><date>2020-08</date><risdate>2020</risdate><volume>14</volume><issue>8</issue><spage>1077</spage><epage>1086</epage><pages>1077-1086</pages><issn>1932-6254</issn><eissn>1932-7005</eissn><abstract>Parkinson's disease (PD) is the most common neurodegenerative disorder of movement worldwide. To date, only symptomatic treatments are available. Implantation of collagen‐encapsulated human umbilical cord mesenchymal stem cells (hUC‐MSCs) is being developed as a novel therapeutic approach to potentially modify PD progression. However, implanted collagen scaffolds may induce a host tissue response. To gain insight into such response, hUC‐MSCs were encapsulated into collagen hydrogels and implanted into the striatum of hemi‐Parkinsonian male Sprague–Dawley rats. One or 14 days after implantation, the area of interest was dissected using a cryostat. Total protein extracts were subjected to tryptic digestion and subsequent LC–MS/MS analyses for protein expression profiling. Univariate and multivariate analyses were performed to identify differentially expressed protein profiles with subsequent gene ontology and pathway analysis for biological interpretation of the data; 2,219 proteins were identified by MaxQuant at 1% false discovery rate. A high correlation of label‐free quantification (LFQ) protein values between biological replicates (r = .95) was observed. No significant differences were observed between brains treated with encapsulated hUC‐MSCs compared to appropriate controls. Proteomic data were highly robust and reproducible, indicating the suitability of this approach to map differential protein expression caused by the implants. The lack of differences between conditions suggests that the effects of implantation may be minimal. Alternatively, effects may only have been focal and/or could have been masked by nonrelevant high‐abundant proteins. For follow‐up assessment of local changes, a more accurate dissection technique, such as laser micro dissection, and analysis method are recommended.</abstract><cop>Hoboken</cop><pub>Hindawi Limited</pub><pmid>32548924</pmid><doi>10.1002/term.3081</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3630-0094</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Basal ganglia Central nervous system diseases Collagen collagen hydrogels Dissection Encapsulation Hydrogels Implantation Medical treatment Mesenchymal stem cells Movement disorders Neostriatum Neurodegenerative diseases Parkinson's disease Protein expression Proteins proteomics rat model Regenerative medicine Stem cell transplantation Stem cells Tissue engineering Umbilical cord |
title | Proteomic profiling of striatal tissue of a rat model of Parkinson's disease after implantation of collagen‐encapsulated human umbilical cord mesenchymal stem cells |
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