Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro

Bckground Stem cells, which have the ability to differentiate into insulin-producing cells (IPCs), would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations of availability and allogeneic rejection. Therefore, the utilization of stem cells is...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Chinese medical journal 2007-05, Vol.120 (9), p.771-776
Hauptverfasser: Sun, Yu, Chen, Li, Hou, Xin-guo, Hou, Wei-kai, Dong, Jian-jun, Sun, Lei, Tang, Kuan-xiao, Wang, Bin, Song, Jun, Li, Hui, Wang, Ke-xin
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 776
container_issue 9
container_start_page 771
container_title Chinese medical journal
container_volume 120
creator Sun, Yu
Chen, Li
Hou, Xin-guo
Hou, Wei-kai
Dong, Jian-jun
Sun, Lei
Tang, Kuan-xiao
Wang, Bin
Song, Jun
Li, Hui
Wang, Ke-xin
description Bckground Stem cells, which have the ability to differentiate into insulin-producing cells (IPCs), would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations of availability and allogeneic rejection. Therefore, the utilization of stem cells is becoming the most promising therapy for diabetes mellitus (DM). Here, we studied the differentiation capacity of the diabetic patient's bone marrow-derived mesenchymal stem cells (MSCs) and tested the feasibility of using MSCs for β-cell replacement. Methods Bone marrow-derived MSCs were obtained from 10 DM patients (5 type 1 DM and 5 type 2 DM) and induced to IPCs under a three-stage protocol. Representative cell surface antigen expression profiles of MSCs were analysed by flow cytometric analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect multiple genes related to pancreatic β-cell development and function. The identity of the IPCs was illustrated by the analysis of morphology, ditizone staining and immunocytochemistry. Release of insulin by these cells was confirmed by immunoradioassay. Results Flow cytometric analysis of MSCs at passage 3 showed that these cells expressed high levels of CD29 (98.28%), CD44 (99.56%) and CD106 (98.34%). Typical islet-like cell clusters were observed at the end of the protocol (18 days). Ditizone staining and immunohistochemistry for insulin were both positive. These differentiated cells at stage 2 (10 days) expressed nestin, pancreatic duodenal homeobox-1 (PDX-1), Neurogenin3, Pax4, insulin, glucagon, but at stage 3 (18 days) we observed the high expression of PDX-1, insulin, glucagon. Insulin was secreted by these cells in response to different concentrations of glucose stimulation in a regulated manner (P〈0.05). Conclusions Bone marrow-derived MSCs from DM patients can differentiate into functional IPCs under certain conditions in vitro. Using diabetic patient's own bone marrow-derived MSCs as a source of autologous IPCs for β-cell reDlacement would be feasible.
doi_str_mv 10.1097/00029330-200705010-00007
format Article
fullrecord <record><control><sourceid>wanfang_jour_proqu</sourceid><recordid>TN_cdi_wanfang_journals_zhcmj200709007</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><cqvip_id>24458523</cqvip_id><wanfj_id>zhcmj200709007</wanfj_id><sourcerecordid>zhcmj200709007</sourcerecordid><originalsourceid>FETCH-LOGICAL-c421t-721fe04e7e395f461ef7ceefe1c837b13f877dfeeee5a53a916f5bcaab6632753</originalsourceid><addsrcrecordid>eNpFUctuFDEQtBCILEl-AVkcuBn8GNvrIwokIEXiAmfL42nvepmxN_ZMouTrcZKB-NCWWlXV3VUIYUY_MWr0Z0opN0JQwinVVFJGSWtR_QptuOw4kapjr9GGCqWIMsacoHe1HhpJSq3eohOmpWCM6Q16-BpDgAJpjm6OOeEccJ8T4MmVku_IACXewoAnqJD8_n5yI64zTNjDOFYcSp7wEF0Pc_T42CSaUsUxzbmVuowxkWPJw-Jj2q2cmPBtnEs-Q2-CGyucr_8p-n357dfFd3L98-rHxZdr4jvOZqI5C0A70CCMDJ1iELQHCMD8VuieibDVegjQnnRSOMNUkL13rldK8HboKfr4rHvnUnBpZw95KalNtA97Px2eLDStvADbxjcL1NlOsT7u7BLkpdrmtKIdMw24fQb6kmstEOyxxGbYvWXUPgZk_wVk_wdknwJq1PfrjKWfYHghrok0wIdVe5_T7qbZZnvn_4Q4guVdJ7eSC_EXvHOZtA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70560419</pqid></control><display><type>article</type><title>Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Sun, Yu ; Chen, Li ; Hou, Xin-guo ; Hou, Wei-kai ; Dong, Jian-jun ; Sun, Lei ; Tang, Kuan-xiao ; Wang, Bin ; Song, Jun ; Li, Hui ; Wang, Ke-xin</creator><creatorcontrib>Sun, Yu ; Chen, Li ; Hou, Xin-guo ; Hou, Wei-kai ; Dong, Jian-jun ; Sun, Lei ; Tang, Kuan-xiao ; Wang, Bin ; Song, Jun ; Li, Hui ; Wang, Ke-xin</creatorcontrib><description>Bckground Stem cells, which have the ability to differentiate into insulin-producing cells (IPCs), would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations of availability and allogeneic rejection. Therefore, the utilization of stem cells is becoming the most promising therapy for diabetes mellitus (DM). Here, we studied the differentiation capacity of the diabetic patient's bone marrow-derived mesenchymal stem cells (MSCs) and tested the feasibility of using MSCs for β-cell replacement. Methods Bone marrow-derived MSCs were obtained from 10 DM patients (5 type 1 DM and 5 type 2 DM) and induced to IPCs under a three-stage protocol. Representative cell surface antigen expression profiles of MSCs were analysed by flow cytometric analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect multiple genes related to pancreatic β-cell development and function. The identity of the IPCs was illustrated by the analysis of morphology, ditizone staining and immunocytochemistry. Release of insulin by these cells was confirmed by immunoradioassay. Results Flow cytometric analysis of MSCs at passage 3 showed that these cells expressed high levels of CD29 (98.28%), CD44 (99.56%) and CD106 (98.34%). Typical islet-like cell clusters were observed at the end of the protocol (18 days). Ditizone staining and immunohistochemistry for insulin were both positive. These differentiated cells at stage 2 (10 days) expressed nestin, pancreatic duodenal homeobox-1 (PDX-1), Neurogenin3, Pax4, insulin, glucagon, but at stage 3 (18 days) we observed the high expression of PDX-1, insulin, glucagon. Insulin was secreted by these cells in response to different concentrations of glucose stimulation in a regulated manner (P〈0.05). Conclusions Bone marrow-derived MSCs from DM patients can differentiate into functional IPCs under certain conditions in vitro. Using diabetic patient's own bone marrow-derived MSCs as a source of autologous IPCs for β-cell reDlacement would be feasible.</description><identifier>ISSN: 0366-6999</identifier><identifier>EISSN: 2542-5641</identifier><identifier>DOI: 10.1097/00029330-200705010-00007</identifier><identifier>PMID: 17531117</identifier><language>eng</language><publisher>China: Department of Endocrinology, Qilu Hospital, Shandong University,Jinan 250012, China%Yuhuangding Hospital, Yantai 264000, China</publisher><subject>Adult ; Bone Marrow Cells - cytology ; Cell Differentiation ; Diabetes Mellitus - therapy ; Female ; Glucose - pharmacology ; Humans ; Insulin - biosynthesis ; Insulin - genetics ; Islets of Langerhans Transplantation ; Male ; Mesenchymal Stromal Cells - cytology ; Phenotype ; 糖尿病患者 ; 细胞分化 ; 胰岛素分泌细胞 ; 骨髓间充质干细胞</subject><ispartof>Chinese medical journal, 2007-05, Vol.120 (9), p.771-776</ispartof><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-721fe04e7e395f461ef7ceefe1c837b13f877dfeeee5a53a916f5bcaab6632753</citedby><cites>FETCH-LOGICAL-c421t-721fe04e7e395f461ef7ceefe1c837b13f877dfeeee5a53a916f5bcaab6632753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/85656X/85656X.jpg</thumbnail><link.rule.ids>314,780,784,864,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17531117$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Yu</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Hou, Xin-guo</creatorcontrib><creatorcontrib>Hou, Wei-kai</creatorcontrib><creatorcontrib>Dong, Jian-jun</creatorcontrib><creatorcontrib>Sun, Lei</creatorcontrib><creatorcontrib>Tang, Kuan-xiao</creatorcontrib><creatorcontrib>Wang, Bin</creatorcontrib><creatorcontrib>Song, Jun</creatorcontrib><creatorcontrib>Li, Hui</creatorcontrib><creatorcontrib>Wang, Ke-xin</creatorcontrib><title>Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro</title><title>Chinese medical journal</title><addtitle>Chinese Medical Journal</addtitle><description>Bckground Stem cells, which have the ability to differentiate into insulin-producing cells (IPCs), would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations of availability and allogeneic rejection. Therefore, the utilization of stem cells is becoming the most promising therapy for diabetes mellitus (DM). Here, we studied the differentiation capacity of the diabetic patient's bone marrow-derived mesenchymal stem cells (MSCs) and tested the feasibility of using MSCs for β-cell replacement. Methods Bone marrow-derived MSCs were obtained from 10 DM patients (5 type 1 DM and 5 type 2 DM) and induced to IPCs under a three-stage protocol. Representative cell surface antigen expression profiles of MSCs were analysed by flow cytometric analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect multiple genes related to pancreatic β-cell development and function. The identity of the IPCs was illustrated by the analysis of morphology, ditizone staining and immunocytochemistry. Release of insulin by these cells was confirmed by immunoradioassay. Results Flow cytometric analysis of MSCs at passage 3 showed that these cells expressed high levels of CD29 (98.28%), CD44 (99.56%) and CD106 (98.34%). Typical islet-like cell clusters were observed at the end of the protocol (18 days). Ditizone staining and immunohistochemistry for insulin were both positive. These differentiated cells at stage 2 (10 days) expressed nestin, pancreatic duodenal homeobox-1 (PDX-1), Neurogenin3, Pax4, insulin, glucagon, but at stage 3 (18 days) we observed the high expression of PDX-1, insulin, glucagon. Insulin was secreted by these cells in response to different concentrations of glucose stimulation in a regulated manner (P〈0.05). Conclusions Bone marrow-derived MSCs from DM patients can differentiate into functional IPCs under certain conditions in vitro. Using diabetic patient's own bone marrow-derived MSCs as a source of autologous IPCs for β-cell reDlacement would be feasible.</description><subject>Adult</subject><subject>Bone Marrow Cells - cytology</subject><subject>Cell Differentiation</subject><subject>Diabetes Mellitus - therapy</subject><subject>Female</subject><subject>Glucose - pharmacology</subject><subject>Humans</subject><subject>Insulin - biosynthesis</subject><subject>Insulin - genetics</subject><subject>Islets of Langerhans Transplantation</subject><subject>Male</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Phenotype</subject><subject>糖尿病患者</subject><subject>细胞分化</subject><subject>胰岛素分泌细胞</subject><subject>骨髓间充质干细胞</subject><issn>0366-6999</issn><issn>2542-5641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUctuFDEQtBCILEl-AVkcuBn8GNvrIwokIEXiAmfL42nvepmxN_ZMouTrcZKB-NCWWlXV3VUIYUY_MWr0Z0opN0JQwinVVFJGSWtR_QptuOw4kapjr9GGCqWIMsacoHe1HhpJSq3eohOmpWCM6Q16-BpDgAJpjm6OOeEccJ8T4MmVku_IACXewoAnqJD8_n5yI64zTNjDOFYcSp7wEF0Pc_T42CSaUsUxzbmVuowxkWPJw-Jj2q2cmPBtnEs-Q2-CGyucr_8p-n357dfFd3L98-rHxZdr4jvOZqI5C0A70CCMDJ1iELQHCMD8VuieibDVegjQnnRSOMNUkL13rldK8HboKfr4rHvnUnBpZw95KalNtA97Px2eLDStvADbxjcL1NlOsT7u7BLkpdrmtKIdMw24fQb6kmstEOyxxGbYvWXUPgZk_wVk_wdknwJq1PfrjKWfYHghrok0wIdVe5_T7qbZZnvn_4Q4guVdJ7eSC_EXvHOZtA</recordid><startdate>20070505</startdate><enddate>20070505</enddate><creator>Sun, Yu</creator><creator>Chen, Li</creator><creator>Hou, Xin-guo</creator><creator>Hou, Wei-kai</creator><creator>Dong, Jian-jun</creator><creator>Sun, Lei</creator><creator>Tang, Kuan-xiao</creator><creator>Wang, Bin</creator><creator>Song, Jun</creator><creator>Li, Hui</creator><creator>Wang, Ke-xin</creator><general>Department of Endocrinology, Qilu Hospital, Shandong University,Jinan 250012, China%Yuhuangding Hospital, Yantai 264000, China</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</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><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope></search><sort><creationdate>20070505</creationdate><title>Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro</title><author>Sun, Yu ; Chen, Li ; Hou, Xin-guo ; Hou, Wei-kai ; Dong, Jian-jun ; Sun, Lei ; Tang, Kuan-xiao ; Wang, Bin ; Song, Jun ; Li, Hui ; Wang, Ke-xin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-721fe04e7e395f461ef7ceefe1c837b13f877dfeeee5a53a916f5bcaab6632753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Bone Marrow Cells - cytology</topic><topic>Cell Differentiation</topic><topic>Diabetes Mellitus - therapy</topic><topic>Female</topic><topic>Glucose - pharmacology</topic><topic>Humans</topic><topic>Insulin - biosynthesis</topic><topic>Insulin - genetics</topic><topic>Islets of Langerhans Transplantation</topic><topic>Male</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Phenotype</topic><topic>糖尿病患者</topic><topic>细胞分化</topic><topic>胰岛素分泌细胞</topic><topic>骨髓间充质干细胞</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Yu</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Hou, Xin-guo</creatorcontrib><creatorcontrib>Hou, Wei-kai</creatorcontrib><creatorcontrib>Dong, Jian-jun</creatorcontrib><creatorcontrib>Sun, Lei</creatorcontrib><creatorcontrib>Tang, Kuan-xiao</creatorcontrib><creatorcontrib>Wang, Bin</creatorcontrib><creatorcontrib>Song, Jun</creatorcontrib><creatorcontrib>Li, Hui</creatorcontrib><creatorcontrib>Wang, Ke-xin</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</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><collection>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><jtitle>Chinese medical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Yu</au><au>Chen, Li</au><au>Hou, Xin-guo</au><au>Hou, Wei-kai</au><au>Dong, Jian-jun</au><au>Sun, Lei</au><au>Tang, Kuan-xiao</au><au>Wang, Bin</au><au>Song, Jun</au><au>Li, Hui</au><au>Wang, Ke-xin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro</atitle><jtitle>Chinese medical journal</jtitle><addtitle>Chinese Medical Journal</addtitle><date>2007-05-05</date><risdate>2007</risdate><volume>120</volume><issue>9</issue><spage>771</spage><epage>776</epage><pages>771-776</pages><issn>0366-6999</issn><eissn>2542-5641</eissn><abstract>Bckground Stem cells, which have the ability to differentiate into insulin-producing cells (IPCs), would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations of availability and allogeneic rejection. Therefore, the utilization of stem cells is becoming the most promising therapy for diabetes mellitus (DM). Here, we studied the differentiation capacity of the diabetic patient's bone marrow-derived mesenchymal stem cells (MSCs) and tested the feasibility of using MSCs for β-cell replacement. Methods Bone marrow-derived MSCs were obtained from 10 DM patients (5 type 1 DM and 5 type 2 DM) and induced to IPCs under a three-stage protocol. Representative cell surface antigen expression profiles of MSCs were analysed by flow cytometric analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect multiple genes related to pancreatic β-cell development and function. The identity of the IPCs was illustrated by the analysis of morphology, ditizone staining and immunocytochemistry. Release of insulin by these cells was confirmed by immunoradioassay. Results Flow cytometric analysis of MSCs at passage 3 showed that these cells expressed high levels of CD29 (98.28%), CD44 (99.56%) and CD106 (98.34%). Typical islet-like cell clusters were observed at the end of the protocol (18 days). Ditizone staining and immunohistochemistry for insulin were both positive. These differentiated cells at stage 2 (10 days) expressed nestin, pancreatic duodenal homeobox-1 (PDX-1), Neurogenin3, Pax4, insulin, glucagon, but at stage 3 (18 days) we observed the high expression of PDX-1, insulin, glucagon. Insulin was secreted by these cells in response to different concentrations of glucose stimulation in a regulated manner (P〈0.05). Conclusions Bone marrow-derived MSCs from DM patients can differentiate into functional IPCs under certain conditions in vitro. Using diabetic patient's own bone marrow-derived MSCs as a source of autologous IPCs for β-cell reDlacement would be feasible.</abstract><cop>China</cop><pub>Department of Endocrinology, Qilu Hospital, Shandong University,Jinan 250012, China%Yuhuangding Hospital, Yantai 264000, China</pub><pmid>17531117</pmid><doi>10.1097/00029330-200705010-00007</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0366-6999
ispartof Chinese medical journal, 2007-05, Vol.120 (9), p.771-776
issn 0366-6999
2542-5641
language eng
recordid cdi_wanfang_journals_zhcmj200709007
source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Adult
Bone Marrow Cells - cytology
Cell Differentiation
Diabetes Mellitus - therapy
Female
Glucose - pharmacology
Humans
Insulin - biosynthesis
Insulin - genetics
Islets of Langerhans Transplantation
Male
Mesenchymal Stromal Cells - cytology
Phenotype
糖尿病患者
细胞分化
胰岛素分泌细胞
骨髓间充质干细胞
title Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T10%3A25%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wanfang_jour_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Differentiation%20of%20bone%20marrow-derived%20mesenchymal%20stem%20cells%20from%20diabetic%20patients%20into%20insulin-producing%20cells%20in%20vitro&rft.jtitle=Chinese%20medical%20journal&rft.au=Sun,%20Yu&rft.date=2007-05-05&rft.volume=120&rft.issue=9&rft.spage=771&rft.epage=776&rft.pages=771-776&rft.issn=0366-6999&rft.eissn=2542-5641&rft_id=info:doi/10.1097/00029330-200705010-00007&rft_dat=%3Cwanfang_jour_proqu%3Ezhcmj200709007%3C/wanfang_jour_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70560419&rft_id=info:pmid/17531117&rft_cqvip_id=24458523&rft_wanfj_id=zhcmj200709007&rfr_iscdi=true