Mesenchymal Stem Cells Reduce Intervertebral Disc Fibrosis and Facilitate Repair
Intervertebral disc degeneration is associated with back pain and radiculopathy which, being a leading cause of disability, seriously affects the quality of life and presents a hefty burden to society. There is no effective intervention for the disease and the etiology remains unclear. Here, we show...
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creator | Leung, Victor Y.L. Aladin, Darwesh M.K. Lv, Fengjuan Tam, Vivian Sun, Yi Lau, Roy Y.C. Hung, Siu‐Chun Ngan, Alfonso H.W. Tang, Bin Lim, Chwee Teck Wu, Ed X. Luk, Keith D.K. Lu, William W. Masuda, Koichi Chan, Danny Cheung, Kenneth M.C. |
description | Intervertebral disc degeneration is associated with back pain and radiculopathy which, being a leading cause of disability, seriously affects the quality of life and presents a hefty burden to society. There is no effective intervention for the disease and the etiology remains unclear. Here, we show that disc degeneration exhibits features of fibrosis in humans and confirmed this in a puncture‐induced disc degeneration (PDD) model in rabbit. Implantation of bone marrow‐derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in the nucleus pulposus with effective preservation of mechanical properties and overall spinal function. We showed that the presence of MSCs can suppress abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining proper fibrillar properties and function. As collagen fibrils can regulate progenitor cell activities, our finding provides new insight to the limited self‐repair capability of the intervertebral disc and importantly the mechanism by which MSCs may potentiate tissue regeneration through regulating collagen fibrillogenesis in the context of fibrotic diseases. Stem Cells 2014;32:2164–2177 |
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There is no effective intervention for the disease and the etiology remains unclear. Here, we show that disc degeneration exhibits features of fibrosis in humans and confirmed this in a puncture‐induced disc degeneration (PDD) model in rabbit. Implantation of bone marrow‐derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in the nucleus pulposus with effective preservation of mechanical properties and overall spinal function. We showed that the presence of MSCs can suppress abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining proper fibrillar properties and function. As collagen fibrils can regulate progenitor cell activities, our finding provides new insight to the limited self‐repair capability of the intervertebral disc and importantly the mechanism by which MSCs may potentiate tissue regeneration through regulating collagen fibrillogenesis in the context of fibrotic diseases. Stem Cells 2014;32:2164–2177</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.1717</identifier><identifier>PMID: 24737495</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Animals ; Bone marrow ; Collagen ; Collagen fibril ; Compressive Strength ; Disc degeneration ; Disease Models, Animal ; Fibrillogenesis ; Fibrosis ; Fibrosis - therapy ; Humans ; Immunohistochemistry ; Intervertebral Disc - metabolism ; Intervertebral Disc - pathology ; Intervertebral Disc Degeneration - pathology ; Intervertebral Disc Degeneration - therapy ; Matrix metalloproteinase 12 ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal stem cells/multipotent stromal cells ; Microscopy, Atomic Force ; Microscopy, Electron, Scanning ; Rabbits ; Range of Motion, Articular ; Stem cells ; Transcriptome</subject><ispartof>Stem cells (Dayton, Ohio), 2014-08, Vol.32 (8), p.2164-2177</ispartof><rights>2014 AlphaMed Press</rights><rights>2014 AlphaMed Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4217-11af03dfd704a29afcf47a0fdce607430ef1ca2f9130f315f7f31b89ceeca3c13</citedby><cites>FETCH-LOGICAL-c4217-11af03dfd704a29afcf47a0fdce607430ef1ca2f9130f315f7f31b89ceeca3c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24737495$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leung, Victor Y.L.</creatorcontrib><creatorcontrib>Aladin, Darwesh M.K.</creatorcontrib><creatorcontrib>Lv, Fengjuan</creatorcontrib><creatorcontrib>Tam, Vivian</creatorcontrib><creatorcontrib>Sun, Yi</creatorcontrib><creatorcontrib>Lau, Roy Y.C.</creatorcontrib><creatorcontrib>Hung, Siu‐Chun</creatorcontrib><creatorcontrib>Ngan, Alfonso H.W.</creatorcontrib><creatorcontrib>Tang, Bin</creatorcontrib><creatorcontrib>Lim, Chwee Teck</creatorcontrib><creatorcontrib>Wu, Ed X.</creatorcontrib><creatorcontrib>Luk, Keith D.K.</creatorcontrib><creatorcontrib>Lu, William W.</creatorcontrib><creatorcontrib>Masuda, Koichi</creatorcontrib><creatorcontrib>Chan, Danny</creatorcontrib><creatorcontrib>Cheung, Kenneth M.C.</creatorcontrib><title>Mesenchymal Stem Cells Reduce Intervertebral Disc Fibrosis and Facilitate Repair</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>Intervertebral disc degeneration is associated with back pain and radiculopathy which, being a leading cause of disability, seriously affects the quality of life and presents a hefty burden to society. There is no effective intervention for the disease and the etiology remains unclear. Here, we show that disc degeneration exhibits features of fibrosis in humans and confirmed this in a puncture‐induced disc degeneration (PDD) model in rabbit. Implantation of bone marrow‐derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in the nucleus pulposus with effective preservation of mechanical properties and overall spinal function. We showed that the presence of MSCs can suppress abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining proper fibrillar properties and function. As collagen fibrils can regulate progenitor cell activities, our finding provides new insight to the limited self‐repair capability of the intervertebral disc and importantly the mechanism by which MSCs may potentiate tissue regeneration through regulating collagen fibrillogenesis in the context of fibrotic diseases. Stem Cells 2014;32:2164–2177</description><subject>Animals</subject><subject>Bone marrow</subject><subject>Collagen</subject><subject>Collagen fibril</subject><subject>Compressive Strength</subject><subject>Disc degeneration</subject><subject>Disease Models, Animal</subject><subject>Fibrillogenesis</subject><subject>Fibrosis</subject><subject>Fibrosis - therapy</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intervertebral Disc - metabolism</subject><subject>Intervertebral Disc - pathology</subject><subject>Intervertebral Disc Degeneration - pathology</subject><subject>Intervertebral Disc Degeneration - therapy</subject><subject>Matrix metalloproteinase 12</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal stem cells/multipotent stromal cells</subject><subject>Microscopy, Atomic Force</subject><subject>Microscopy, Electron, Scanning</subject><subject>Rabbits</subject><subject>Range of Motion, Articular</subject><subject>Stem cells</subject><subject>Transcriptome</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0UFLwzAYBuAgipvTg39ACl700C1fkzbtUeamg4ni5rmk6RfsaLuZtMr-vambHgTBS5LDk5fkewk5BzoESoORbbAaggBxQPoQ8sTnCcSH7kyjyA9pkvTIibUrSoGHcXxMegEXTPAk7JOnB7RYq9dtJUtv4XK8MZal9Z4xbxV6s7pB846mwcw4cFtY5U2LzKxtYT1Z595UqqIsGtmgu7KRhTklR1qWFs_2-4C8TCfL8b0_f7ybjW_mvuIBCB9AaspynQvKZZBIrTQXkupcYUQFZxQ1KBnoBBjVDEIt3JrFiUJUkilgA3K1y92Y9VuLtkkr9zj3dlnjurWpm4OIeQSc_4uGjEbAHL38RVfr1tTuI50KGcRhLJy63inlBmEN6nRjikqabQo07RpJu0bSrhFnL_aJbVZh_iO_K3BgtAMfRYnbv5PSxXLy8BX5Ce8dlQI</recordid><startdate>201408</startdate><enddate>201408</enddate><creator>Leung, Victor Y.L.</creator><creator>Aladin, Darwesh M.K.</creator><creator>Lv, Fengjuan</creator><creator>Tam, Vivian</creator><creator>Sun, Yi</creator><creator>Lau, Roy Y.C.</creator><creator>Hung, Siu‐Chun</creator><creator>Ngan, Alfonso H.W.</creator><creator>Tang, Bin</creator><creator>Lim, Chwee Teck</creator><creator>Wu, Ed X.</creator><creator>Luk, Keith D.K.</creator><creator>Lu, William W.</creator><creator>Masuda, Koichi</creator><creator>Chan, Danny</creator><creator>Cheung, Kenneth M.C.</creator><general>Oxford University Press</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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201408</creationdate><title>Mesenchymal Stem Cells Reduce Intervertebral Disc Fibrosis and Facilitate Repair</title><author>Leung, Victor Y.L. ; 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There is no effective intervention for the disease and the etiology remains unclear. Here, we show that disc degeneration exhibits features of fibrosis in humans and confirmed this in a puncture‐induced disc degeneration (PDD) model in rabbit. Implantation of bone marrow‐derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in the nucleus pulposus with effective preservation of mechanical properties and overall spinal function. We showed that the presence of MSCs can suppress abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining proper fibrillar properties and function. As collagen fibrils can regulate progenitor cell activities, our finding provides new insight to the limited self‐repair capability of the intervertebral disc and importantly the mechanism by which MSCs may potentiate tissue regeneration through regulating collagen fibrillogenesis in the context of fibrotic diseases. Stem Cells 2014;32:2164–2177</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>24737495</pmid><doi>10.1002/stem.1717</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Bone marrow Collagen Collagen fibril Compressive Strength Disc degeneration Disease Models, Animal Fibrillogenesis Fibrosis Fibrosis - therapy Humans Immunohistochemistry Intervertebral Disc - metabolism Intervertebral Disc - pathology Intervertebral Disc Degeneration - pathology Intervertebral Disc Degeneration - therapy Matrix metalloproteinase 12 Mesenchymal Stem Cell Transplantation - methods Mesenchymal stem cells/multipotent stromal cells Microscopy, Atomic Force Microscopy, Electron, Scanning Rabbits Range of Motion, Articular Stem cells Transcriptome |
title | Mesenchymal Stem Cells Reduce Intervertebral Disc Fibrosis and Facilitate Repair |
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