Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow–Derived Mesenchymal Stem Cells
Background: Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM. Purpose: To investigate the effect of fresh autologous BM on tendon...
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| Veröffentlicht in: | The American journal of sports medicine 2019-09, Vol.47 (11), p.2729-2736 |
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| creator | Lu, Jun Chamberlain, Connie S. Ji, Ming-liang Saether, Erin E. Leiferman, Ellen M. Li, Wan-Ju Vanderby, Ray |
| description | Background:
Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM.
Purpose:
To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model.
Study Design:
Controlled laboratory study.
Methods:
An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery.
Results:
The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks (P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group (P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery (P < .05). Load to failure showed similar trends to stiffness.
Conclusion:
These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization.
Clinical Relevance:
Fresh autologous BM could be a treatment option for this disorder. |
| doi_str_mv | 10.1177/0363546519862284 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2264225271</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0363546519862284</sage_id><sourcerecordid>2283932126</sourcerecordid><originalsourceid>FETCH-LOGICAL-c365t-8fbbdf56a8d3eccc6c90be93d2ecae27324a619529ab55bf32ba2ba8fe564dbd3</originalsourceid><addsrcrecordid>eNp1kc9u1DAQxi0EokvhzglZ4sLFENuxk3DbLi1F6goJlnM0sSfbVI692AnQG-_AC_BsPAletvxRJSRLI2t-3zcz-gh5zIvnnFfVi0JqqUqteFNrIeryDllwpQSTUqu7ZLFvs33_iDxI6aooCl7p-j45klzKppLNgnzfoLfBsymwk-CRniO4wW_p4CnQdzDR0y9TBAZxGszsINJf1Gb2Hh1dB4vuJV3SVRh3EIcUPA09PYuYLulynoIL2zCng2YNMYbPFLz99__j67dXGIdPaOkaE3pzeT2Co-8nHOkKnUsPyb0eXMJHN_WYfDg73azO2cXb129Wywtm8q0Tq_uus73SUFuJxhhtmqLDRlqBBlBUUpSgeaNEA51SXS9FB_nVPSpd2s7KY_Ls4LuL4eOMaWrHIZm8AXjMN7RC6FIIJSqe0ae30KswR5-3y1QtGym40JkqDpSJIaWIfbuLwwjxuuVFu0-vvZ1eljy5MZ67Ee0fwe-4MsAOQIIt_p36X8OfM4GkAA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2283932126</pqid></control><display><type>article</type><title>Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow–Derived Mesenchymal Stem Cells</title><source>SAGE Complete A-Z List</source><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Lu, Jun ; Chamberlain, Connie S. ; Ji, Ming-liang ; Saether, Erin E. ; Leiferman, Ellen M. ; Li, Wan-Ju ; Vanderby, Ray</creator><creatorcontrib>Lu, Jun ; Chamberlain, Connie S. ; Ji, Ming-liang ; Saether, Erin E. ; Leiferman, Ellen M. ; Li, Wan-Ju ; Vanderby, Ray</creatorcontrib><description>Background:
Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM.
Purpose:
To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model.
Study Design:
Controlled laboratory study.
Methods:
An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery.
Results:
The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks (P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group (P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery (P < .05). Load to failure showed similar trends to stiffness.
Conclusion:
These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization.
Clinical Relevance:
Fresh autologous BM could be a treatment option for this disorder.</description><identifier>ISSN: 0363-5465</identifier><identifier>EISSN: 1552-3365</identifier><identifier>DOI: 10.1177/0363546519862284</identifier><identifier>PMID: 31339739</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Biomechanics ; Bone and Bones - physiology ; Bone and Bones - surgery ; Bone marrow ; Bone Marrow Transplantation ; Male ; Mesenchymal Stem Cell Transplantation ; Models, Animal ; Random Allocation ; Rats, Sprague-Dawley ; Rodents ; Sports medicine ; Tendons - physiology ; Tendons - transplantation ; Transplantation, Autologous ; Wound Healing - physiology</subject><ispartof>The American journal of sports medicine, 2019-09, Vol.47 (11), p.2729-2736</ispartof><rights>2019 The Author(s)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-8fbbdf56a8d3eccc6c90be93d2ecae27324a619529ab55bf32ba2ba8fe564dbd3</citedby><cites>FETCH-LOGICAL-c365t-8fbbdf56a8d3eccc6c90be93d2ecae27324a619529ab55bf32ba2ba8fe564dbd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0363546519862284$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0363546519862284$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21800,27903,27904,43600,43601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31339739$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Jun</creatorcontrib><creatorcontrib>Chamberlain, Connie S.</creatorcontrib><creatorcontrib>Ji, Ming-liang</creatorcontrib><creatorcontrib>Saether, Erin E.</creatorcontrib><creatorcontrib>Leiferman, Ellen M.</creatorcontrib><creatorcontrib>Li, Wan-Ju</creatorcontrib><creatorcontrib>Vanderby, Ray</creatorcontrib><title>Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow–Derived Mesenchymal Stem Cells</title><title>The American journal of sports medicine</title><addtitle>Am J Sports Med</addtitle><description>Background:
Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM.
Purpose:
To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model.
Study Design:
Controlled laboratory study.
Methods:
An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery.
Results:
The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks (P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group (P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery (P < .05). Load to failure showed similar trends to stiffness.
Conclusion:
These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization.
Clinical Relevance:
Fresh autologous BM could be a treatment option for this disorder.</description><subject>Animals</subject><subject>Biomechanics</subject><subject>Bone and Bones - physiology</subject><subject>Bone and Bones - surgery</subject><subject>Bone marrow</subject><subject>Bone Marrow Transplantation</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Models, Animal</subject><subject>Random Allocation</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Sports medicine</subject><subject>Tendons - physiology</subject><subject>Tendons - transplantation</subject><subject>Transplantation, Autologous</subject><subject>Wound Healing - physiology</subject><issn>0363-5465</issn><issn>1552-3365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9u1DAQxi0EokvhzglZ4sLFENuxk3DbLi1F6goJlnM0sSfbVI692AnQG-_AC_BsPAletvxRJSRLI2t-3zcz-gh5zIvnnFfVi0JqqUqteFNrIeryDllwpQSTUqu7ZLFvs33_iDxI6aooCl7p-j45klzKppLNgnzfoLfBsymwk-CRniO4wW_p4CnQdzDR0y9TBAZxGszsINJf1Gb2Hh1dB4vuJV3SVRh3EIcUPA09PYuYLulynoIL2zCng2YNMYbPFLz99__j67dXGIdPaOkaE3pzeT2Co-8nHOkKnUsPyb0eXMJHN_WYfDg73azO2cXb129Wywtm8q0Tq_uus73SUFuJxhhtmqLDRlqBBlBUUpSgeaNEA51SXS9FB_nVPSpd2s7KY_Ls4LuL4eOMaWrHIZm8AXjMN7RC6FIIJSqe0ae30KswR5-3y1QtGym40JkqDpSJIaWIfbuLwwjxuuVFu0-vvZ1eljy5MZ67Ee0fwe-4MsAOQIIt_p36X8OfM4GkAA</recordid><startdate>201909</startdate><enddate>201909</enddate><creator>Lu, Jun</creator><creator>Chamberlain, Connie S.</creator><creator>Ji, Ming-liang</creator><creator>Saether, Erin E.</creator><creator>Leiferman, Ellen M.</creator><creator>Li, Wan-Ju</creator><creator>Vanderby, Ray</creator><general>SAGE Publications</general><general>Sage Publications Ltd</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>7TS</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>201909</creationdate><title>Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow–Derived Mesenchymal Stem Cells</title><author>Lu, Jun ; Chamberlain, Connie S. ; Ji, Ming-liang ; Saether, Erin E. ; Leiferman, Ellen M. ; Li, Wan-Ju ; Vanderby, Ray</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-8fbbdf56a8d3eccc6c90be93d2ecae27324a619529ab55bf32ba2ba8fe564dbd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Biomechanics</topic><topic>Bone and Bones - physiology</topic><topic>Bone and Bones - surgery</topic><topic>Bone marrow</topic><topic>Bone Marrow Transplantation</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Models, Animal</topic><topic>Random Allocation</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Sports medicine</topic><topic>Tendons - physiology</topic><topic>Tendons - transplantation</topic><topic>Transplantation, Autologous</topic><topic>Wound Healing - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Jun</creatorcontrib><creatorcontrib>Chamberlain, Connie S.</creatorcontrib><creatorcontrib>Ji, Ming-liang</creatorcontrib><creatorcontrib>Saether, Erin E.</creatorcontrib><creatorcontrib>Leiferman, Ellen M.</creatorcontrib><creatorcontrib>Li, Wan-Ju</creatorcontrib><creatorcontrib>Vanderby, Ray</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Physical Education Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of sports medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Jun</au><au>Chamberlain, Connie S.</au><au>Ji, Ming-liang</au><au>Saether, Erin E.</au><au>Leiferman, Ellen M.</au><au>Li, Wan-Ju</au><au>Vanderby, Ray</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow–Derived Mesenchymal Stem Cells</atitle><jtitle>The American journal of sports medicine</jtitle><addtitle>Am J Sports Med</addtitle><date>2019-09</date><risdate>2019</risdate><volume>47</volume><issue>11</issue><spage>2729</spage><epage>2736</epage><pages>2729-2736</pages><issn>0363-5465</issn><eissn>1552-3365</eissn><abstract>Background:
Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM.
Purpose:
To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model.
Study Design:
Controlled laboratory study.
Methods:
An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery.
Results:
The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks (P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group (P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery (P < .05). Load to failure showed similar trends to stiffness.
Conclusion:
These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization.
Clinical Relevance:
Fresh autologous BM could be a treatment option for this disorder.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>31339739</pmid><doi>10.1177/0363546519862284</doi><tpages>8</tpages></addata></record> |
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| ispartof | The American journal of sports medicine, 2019-09, Vol.47 (11), p.2729-2736 |
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| source | SAGE Complete A-Z List; MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Biomechanics Bone and Bones - physiology Bone and Bones - surgery Bone marrow Bone Marrow Transplantation Male Mesenchymal Stem Cell Transplantation Models, Animal Random Allocation Rats, Sprague-Dawley Rodents Sports medicine Tendons - physiology Tendons - transplantation Transplantation, Autologous Wound Healing - physiology |
| title | Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow–Derived Mesenchymal Stem Cells |
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