Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells
Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow‐derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insuli...
Gespeichert in:
| Veröffentlicht in: | Journal of cellular physiology 2007-04, Vol.211 (1), p.36-44 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 44 |
|---|---|
| container_issue | 1 |
| container_start_page | 36 |
| container_title | Journal of cellular physiology |
| container_volume | 211 |
| creator | Li, Yanhua Zhang, Rui Qiao, Haifa Zhang, Heping Wang, Yunfang Yuan, Hongfeng Liu, Qinbin Liu, Daqing Chen, Lin Pei, Xuetao |
| description | Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow‐derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin‐producing cells by introduction of the pancreatic duodenal homeobox‐1 (PDX‐1). Recombinant adenoviral vector was used to deliver PDX‐1 gene into hMSCs. After being infected with Ad‐PDX‐1, hMSCs were successfully induced to differentiate into insulin‐secreting cells. The differentiated PDX‐1+ hMSCs expressed multiple islet‐cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C‐peptide in a weak glucose‐regulated manner. After the differentiated PDX‐1+ hMSCs were transplanted into STZ‐induced diabetic mice, euglycemia can be obtained within 2 weeks and maintained for at least 42 days. These findings validate the hMSCs model system as a potential basis for enrichment of human beta cells or their precursors, and a possible source for cell replacement therapy in diabetes. J. Cell. Physiol. 211: 36–44, 2007. © 2007 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/jcp.20897 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68981623</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68981623</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4277-e87278c32446a1d9591c77e162e6a2f5ef3a68fbcd25ec9040bb4b92ae9e448d3</originalsourceid><addsrcrecordid>eNp1kEFP2zAYhi20iXbdDvwB5NMkDqa248TxERUoQ4xV6iaQOFiO86UY4qTEjUb_PWYpcNrJBz_vo08PQgeMHjNK-fTBro85zZXcQ2NGlSQiS_knNI5_jKhUsBH6EsIDpVSpJNlHIyY5z2SuxuhuDg10ZuPaBrcVdk3oa9eQddeWvXXNCluo64CrrvV4cXpLGF7FAfFt6SoHJb7vvWmwhwCNvd96U-OwAT-svqLPlakDfNu9E_Tn_Oz37IJc_Zr_mJ1cESu4lARyyWVuEy5EZlipUsWslMAyDpnhVQpVYrK8KmzJU7CKCloUolDcgAIh8jKZoO-DN1791EPYaO_C6wWmgbYPOstVHm1JBI8G0HZtCB1Uet05b7qtZlS_ltSxpP5XMrKHO2lfeCg_yF26CEwH4K-rYft_k76cLd6UZFi42Oj5fWG6R53JRKb65nquL5cX4nypfuqb5AWgzYzY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68981623</pqid></control><display><type>article</type><title>Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Li, Yanhua ; Zhang, Rui ; Qiao, Haifa ; Zhang, Heping ; Wang, Yunfang ; Yuan, Hongfeng ; Liu, Qinbin ; Liu, Daqing ; Chen, Lin ; Pei, Xuetao</creator><creatorcontrib>Li, Yanhua ; Zhang, Rui ; Qiao, Haifa ; Zhang, Heping ; Wang, Yunfang ; Yuan, Hongfeng ; Liu, Qinbin ; Liu, Daqing ; Chen, Lin ; Pei, Xuetao</creatorcontrib><description>Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow‐derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin‐producing cells by introduction of the pancreatic duodenal homeobox‐1 (PDX‐1). Recombinant adenoviral vector was used to deliver PDX‐1 gene into hMSCs. After being infected with Ad‐PDX‐1, hMSCs were successfully induced to differentiate into insulin‐secreting cells. The differentiated PDX‐1+ hMSCs expressed multiple islet‐cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C‐peptide in a weak glucose‐regulated manner. After the differentiated PDX‐1+ hMSCs were transplanted into STZ‐induced diabetic mice, euglycemia can be obtained within 2 weeks and maintained for at least 42 days. These findings validate the hMSCs model system as a potential basis for enrichment of human beta cells or their precursors, and a possible source for cell replacement therapy in diabetes. J. Cell. Physiol. 211: 36–44, 2007. © 2007 Wiley‐Liss, Inc.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.20897</identifier><identifier>PMID: 17226789</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adenoviridae ; Adult ; Animals ; C-Peptide - metabolism ; Cell Differentiation - drug effects ; Diabetes Mellitus, Experimental ; Gene Expression Regulation - drug effects ; Glucose - pharmacology ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Hyperglycemia - pathology ; Insulin - metabolism ; Insulin Secretion ; Insulin-Secreting Cells - cytology ; Insulin-Secreting Cells - drug effects ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - drug effects ; Mice ; Mice, Inbred BALB C ; Potassium Channels - metabolism ; Streptozocin ; Trans-Activators - genetics ; Trans-Activators - metabolism</subject><ispartof>Journal of cellular physiology, 2007-04, Vol.211 (1), p.36-44</ispartof><rights>Copyright © 2007 Wiley‐Liss, Inc.</rights><rights>(c) 2007 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4277-e87278c32446a1d9591c77e162e6a2f5ef3a68fbcd25ec9040bb4b92ae9e448d3</citedby><cites>FETCH-LOGICAL-c4277-e87278c32446a1d9591c77e162e6a2f5ef3a68fbcd25ec9040bb4b92ae9e448d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.20897$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.20897$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17226789$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yanhua</creatorcontrib><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Qiao, Haifa</creatorcontrib><creatorcontrib>Zhang, Heping</creatorcontrib><creatorcontrib>Wang, Yunfang</creatorcontrib><creatorcontrib>Yuan, Hongfeng</creatorcontrib><creatorcontrib>Liu, Qinbin</creatorcontrib><creatorcontrib>Liu, Daqing</creatorcontrib><creatorcontrib>Chen, Lin</creatorcontrib><creatorcontrib>Pei, Xuetao</creatorcontrib><title>Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells</title><title>Journal of cellular physiology</title><addtitle>J. Cell. Physiol</addtitle><description>Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow‐derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin‐producing cells by introduction of the pancreatic duodenal homeobox‐1 (PDX‐1). Recombinant adenoviral vector was used to deliver PDX‐1 gene into hMSCs. After being infected with Ad‐PDX‐1, hMSCs were successfully induced to differentiate into insulin‐secreting cells. The differentiated PDX‐1+ hMSCs expressed multiple islet‐cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C‐peptide in a weak glucose‐regulated manner. After the differentiated PDX‐1+ hMSCs were transplanted into STZ‐induced diabetic mice, euglycemia can be obtained within 2 weeks and maintained for at least 42 days. These findings validate the hMSCs model system as a potential basis for enrichment of human beta cells or their precursors, and a possible source for cell replacement therapy in diabetes. J. Cell. Physiol. 211: 36–44, 2007. © 2007 Wiley‐Liss, Inc.</description><subject>Adenoviridae</subject><subject>Adult</subject><subject>Animals</subject><subject>C-Peptide - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Diabetes Mellitus, Experimental</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glucose - pharmacology</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Hyperglycemia - pathology</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Insulin-Secreting Cells - cytology</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Potassium Channels - metabolism</subject><subject>Streptozocin</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFP2zAYhi20iXbdDvwB5NMkDqa248TxERUoQ4xV6iaQOFiO86UY4qTEjUb_PWYpcNrJBz_vo08PQgeMHjNK-fTBro85zZXcQ2NGlSQiS_knNI5_jKhUsBH6EsIDpVSpJNlHIyY5z2SuxuhuDg10ZuPaBrcVdk3oa9eQddeWvXXNCluo64CrrvV4cXpLGF7FAfFt6SoHJb7vvWmwhwCNvd96U-OwAT-svqLPlakDfNu9E_Tn_Oz37IJc_Zr_mJ1cESu4lARyyWVuEy5EZlipUsWslMAyDpnhVQpVYrK8KmzJU7CKCloUolDcgAIh8jKZoO-DN1791EPYaO_C6wWmgbYPOstVHm1JBI8G0HZtCB1Uet05b7qtZlS_ltSxpP5XMrKHO2lfeCg_yF26CEwH4K-rYft_k76cLd6UZFi42Oj5fWG6R53JRKb65nquL5cX4nypfuqb5AWgzYzY</recordid><startdate>200704</startdate><enddate>200704</enddate><creator>Li, Yanhua</creator><creator>Zhang, Rui</creator><creator>Qiao, Haifa</creator><creator>Zhang, Heping</creator><creator>Wang, Yunfang</creator><creator>Yuan, Hongfeng</creator><creator>Liu, Qinbin</creator><creator>Liu, Daqing</creator><creator>Chen, Lin</creator><creator>Pei, Xuetao</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>200704</creationdate><title>Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells</title><author>Li, Yanhua ; Zhang, Rui ; Qiao, Haifa ; Zhang, Heping ; Wang, Yunfang ; Yuan, Hongfeng ; Liu, Qinbin ; Liu, Daqing ; Chen, Lin ; Pei, Xuetao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4277-e87278c32446a1d9591c77e162e6a2f5ef3a68fbcd25ec9040bb4b92ae9e448d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenoviridae</topic><topic>Adult</topic><topic>Animals</topic><topic>C-Peptide - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Diabetes Mellitus, Experimental</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Glucose - pharmacology</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Hyperglycemia - pathology</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>Insulin-Secreting Cells - cytology</topic><topic>Insulin-Secreting Cells - drug effects</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Potassium Channels - metabolism</topic><topic>Streptozocin</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Yanhua</creatorcontrib><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Qiao, Haifa</creatorcontrib><creatorcontrib>Zhang, Heping</creatorcontrib><creatorcontrib>Wang, Yunfang</creatorcontrib><creatorcontrib>Yuan, Hongfeng</creatorcontrib><creatorcontrib>Liu, Qinbin</creatorcontrib><creatorcontrib>Liu, Daqing</creatorcontrib><creatorcontrib>Chen, Lin</creatorcontrib><creatorcontrib>Pei, Xuetao</creatorcontrib><collection>Istex</collection><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>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Yanhua</au><au>Zhang, Rui</au><au>Qiao, Haifa</au><au>Zhang, Heping</au><au>Wang, Yunfang</au><au>Yuan, Hongfeng</au><au>Liu, Qinbin</au><au>Liu, Daqing</au><au>Chen, Lin</au><au>Pei, Xuetao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J. Cell. Physiol</addtitle><date>2007-04</date><risdate>2007</risdate><volume>211</volume><issue>1</issue><spage>36</spage><epage>44</epage><pages>36-44</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow‐derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin‐producing cells by introduction of the pancreatic duodenal homeobox‐1 (PDX‐1). Recombinant adenoviral vector was used to deliver PDX‐1 gene into hMSCs. After being infected with Ad‐PDX‐1, hMSCs were successfully induced to differentiate into insulin‐secreting cells. The differentiated PDX‐1+ hMSCs expressed multiple islet‐cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C‐peptide in a weak glucose‐regulated manner. After the differentiated PDX‐1+ hMSCs were transplanted into STZ‐induced diabetic mice, euglycemia can be obtained within 2 weeks and maintained for at least 42 days. These findings validate the hMSCs model system as a potential basis for enrichment of human beta cells or their precursors, and a possible source for cell replacement therapy in diabetes. J. Cell. Physiol. 211: 36–44, 2007. © 2007 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>17226789</pmid><doi>10.1002/jcp.20897</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9541 |
| ispartof | Journal of cellular physiology, 2007-04, Vol.211 (1), p.36-44 |
| issn | 0021-9541 1097-4652 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68981623 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adenoviridae Adult Animals C-Peptide - metabolism Cell Differentiation - drug effects Diabetes Mellitus, Experimental Gene Expression Regulation - drug effects Glucose - pharmacology Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Hyperglycemia - pathology Insulin - metabolism Insulin Secretion Insulin-Secreting Cells - cytology Insulin-Secreting Cells - drug effects Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - drug effects Mice Mice, Inbred BALB C Potassium Channels - metabolism Streptozocin Trans-Activators - genetics Trans-Activators - metabolism |
| title | Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T19%3A39%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Generation%20of%20insulin-producing%20cells%20from%20PDX-1%20gene-modified%20human%20mesenchymal%20stem%20cells&rft.jtitle=Journal%20of%20cellular%20physiology&rft.au=Li,%20Yanhua&rft.date=2007-04&rft.volume=211&rft.issue=1&rft.spage=36&rft.epage=44&rft.pages=36-44&rft.issn=0021-9541&rft.eissn=1097-4652&rft_id=info:doi/10.1002/jcp.20897&rft_dat=%3Cproquest_cross%3E68981623%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=68981623&rft_id=info:pmid/17226789&rfr_iscdi=true |