Application of Autogenous Urine-Derived Stem Cell Sheet Enhances Rotator Cuff Healing in a Canine Model

Background: A repaired rotator cuff (RC) often heals with interposed scar tissue, making repairs prone to failure. Urine-derived stem cells (USCs), with robust proliferation ability and multilineage differentiation, can be isolated from urine, avoiding invasive and painful surgical procedures for ha...

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Veröffentlicht in:The American journal of sports medicine 2020-12, Vol.48 (14), p.3454-3466
Hauptverfasser: Chen, Yang, Xu, Yan, Li, Muzhi, Shi, Qiang, Chen, Can
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container_end_page 3466
container_issue 14
container_start_page 3454
container_title The American journal of sports medicine
container_volume 48
creator Chen, Yang
Xu, Yan
Li, Muzhi
Shi, Qiang
Chen, Can
description Background: A repaired rotator cuff (RC) often heals with interposed scar tissue, making repairs prone to failure. Urine-derived stem cells (USCs), with robust proliferation ability and multilineage differentiation, can be isolated from urine, avoiding invasive and painful surgical procedures for harvesting the cells. These advantages make it a novel cell source for autologous transplantation to enhance RC healing. Hypothesis: Implantation of an autogenous USC sheet to the injury site will enhance RC healing. Study Design: Controlled laboratory study. Methods: USCs isolated from urine were cultured using ascorbic acid and transforming growth factor β3 to form a cell sheet. Sixteen male mature beagles underwent bilateral shoulder surgery. The right shoulder underwent infraspinatus tendon (IT) insertion detachment and repair only, and the other was subjected to IT insertion detachment and repair, followed by autogenous USC sheet implantation. Among the animals, 3 received a Dil (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate)- labeled USC sheet implant in the right shoulder and were sacrificed at postoperative 6 weeks for cell tracking. The other animals were sacrificed at postoperative 12 weeks, and the IT-humerus complexes were harvested for gross observation, micro–computed tomography evaluation and histological analysis (n = 5), and mechanical testing (n = 8). Additionally, 13 unpaired canine cadaveric shoulders were included as native controls. Results: Micro–computed tomography analysis showed that the USC sheet group had a significant increase in bone volume/total volume and trabecular thickness at the RC healing site when compared with the control group (P < .05 for all). Histologically, the Dil-labeled USC sheet was still visible at the RC healing site, which suggested that the implanted USCs remained viable at postoperative 6 weeks. Meanwhile, the healing interface in the USC sheet group regenerated significantly more enthesis-like tissue than did that of the control group (P < .05). Additionally, the healing interface in the USC sheet group presented a larger fibrocartilage area, more proteoglycan deposition, and higher collagen birefringence than did that of the control group (P < .05 for all). Biomechanically, the USC sheet group showed significantly higher failure load and stiffness versus the control group (P < .05 for all). Conclusion: A USC sheet was able to enhance RC healing in a canine model. Clinical Relevance: The fi
doi_str_mv 10.1177/0363546520962774
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Urine-derived stem cells (USCs), with robust proliferation ability and multilineage differentiation, can be isolated from urine, avoiding invasive and painful surgical procedures for harvesting the cells. These advantages make it a novel cell source for autologous transplantation to enhance RC healing. Hypothesis: Implantation of an autogenous USC sheet to the injury site will enhance RC healing. Study Design: Controlled laboratory study. Methods: USCs isolated from urine were cultured using ascorbic acid and transforming growth factor β3 to form a cell sheet. Sixteen male mature beagles underwent bilateral shoulder surgery. The right shoulder underwent infraspinatus tendon (IT) insertion detachment and repair only, and the other was subjected to IT insertion detachment and repair, followed by autogenous USC sheet implantation. Among the animals, 3 received a Dil (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate)- labeled USC sheet implant in the right shoulder and were sacrificed at postoperative 6 weeks for cell tracking. The other animals were sacrificed at postoperative 12 weeks, and the IT-humerus complexes were harvested for gross observation, micro–computed tomography evaluation and histological analysis (n = 5), and mechanical testing (n = 8). Additionally, 13 unpaired canine cadaveric shoulders were included as native controls. Results: Micro–computed tomography analysis showed that the USC sheet group had a significant increase in bone volume/total volume and trabecular thickness at the RC healing site when compared with the control group (P &lt; .05 for all). Histologically, the Dil-labeled USC sheet was still visible at the RC healing site, which suggested that the implanted USCs remained viable at postoperative 6 weeks. Meanwhile, the healing interface in the USC sheet group regenerated significantly more enthesis-like tissue than did that of the control group (P &lt; .05). Additionally, the healing interface in the USC sheet group presented a larger fibrocartilage area, more proteoglycan deposition, and higher collagen birefringence than did that of the control group (P &lt; .05 for all). Biomechanically, the USC sheet group showed significantly higher failure load and stiffness versus the control group (P &lt; .05 for all). Conclusion: A USC sheet was able to enhance RC healing in a canine model. Clinical Relevance: The findings of the study showed that USC sheet implantation could serve as a practical application for RC healing.</description><identifier>ISSN: 0363-5465</identifier><identifier>EISSN: 1552-3365</identifier><identifier>DOI: 10.1177/0363546520962774</identifier><identifier>PMID: 33136424</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Biomechanical Phenomena ; Cells, Cultured ; Dogs ; Male ; Rotator cuff ; Rotator Cuff - surgery ; Rotator Cuff Injuries - surgery ; Sports medicine ; Stem Cell Transplantation ; Stem Cells - cytology ; Tomography ; Transplants &amp; implants ; Urine ; Urine - cytology ; Wound Healing ; X-Ray Microtomography</subject><ispartof>The American journal of sports medicine, 2020-12, Vol.48 (14), p.3454-3466</ispartof><rights>2020 The Author(s)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-fde9ea3d2ea9881c3bde9c6e052c30a6a51767898050b0d07ece368ba25d0e03</citedby><cites>FETCH-LOGICAL-c365t-fde9ea3d2ea9881c3bde9c6e052c30a6a51767898050b0d07ece368ba25d0e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0363546520962774$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0363546520962774$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33136424$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Yang</creatorcontrib><creatorcontrib>Xu, Yan</creatorcontrib><creatorcontrib>Li, Muzhi</creatorcontrib><creatorcontrib>Shi, Qiang</creatorcontrib><creatorcontrib>Chen, Can</creatorcontrib><title>Application of Autogenous Urine-Derived Stem Cell Sheet Enhances Rotator Cuff Healing in a Canine Model</title><title>The American journal of sports medicine</title><addtitle>Am J Sports Med</addtitle><description>Background: A repaired rotator cuff (RC) often heals with interposed scar tissue, making repairs prone to failure. Urine-derived stem cells (USCs), with robust proliferation ability and multilineage differentiation, can be isolated from urine, avoiding invasive and painful surgical procedures for harvesting the cells. These advantages make it a novel cell source for autologous transplantation to enhance RC healing. Hypothesis: Implantation of an autogenous USC sheet to the injury site will enhance RC healing. Study Design: Controlled laboratory study. Methods: USCs isolated from urine were cultured using ascorbic acid and transforming growth factor β3 to form a cell sheet. Sixteen male mature beagles underwent bilateral shoulder surgery. The right shoulder underwent infraspinatus tendon (IT) insertion detachment and repair only, and the other was subjected to IT insertion detachment and repair, followed by autogenous USC sheet implantation. Among the animals, 3 received a Dil (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate)- labeled USC sheet implant in the right shoulder and were sacrificed at postoperative 6 weeks for cell tracking. The other animals were sacrificed at postoperative 12 weeks, and the IT-humerus complexes were harvested for gross observation, micro–computed tomography evaluation and histological analysis (n = 5), and mechanical testing (n = 8). Additionally, 13 unpaired canine cadaveric shoulders were included as native controls. Results: Micro–computed tomography analysis showed that the USC sheet group had a significant increase in bone volume/total volume and trabecular thickness at the RC healing site when compared with the control group (P &lt; .05 for all). Histologically, the Dil-labeled USC sheet was still visible at the RC healing site, which suggested that the implanted USCs remained viable at postoperative 6 weeks. Meanwhile, the healing interface in the USC sheet group regenerated significantly more enthesis-like tissue than did that of the control group (P &lt; .05). Additionally, the healing interface in the USC sheet group presented a larger fibrocartilage area, more proteoglycan deposition, and higher collagen birefringence than did that of the control group (P &lt; .05 for all). Biomechanically, the USC sheet group showed significantly higher failure load and stiffness versus the control group (P &lt; .05 for all). Conclusion: A USC sheet was able to enhance RC healing in a canine model. Clinical Relevance: The findings of the study showed that USC sheet implantation could serve as a practical application for RC healing.</description><subject>Animals</subject><subject>Biomechanical Phenomena</subject><subject>Cells, Cultured</subject><subject>Dogs</subject><subject>Male</subject><subject>Rotator cuff</subject><subject>Rotator Cuff - surgery</subject><subject>Rotator Cuff Injuries - surgery</subject><subject>Sports medicine</subject><subject>Stem Cell Transplantation</subject><subject>Stem Cells - cytology</subject><subject>Tomography</subject><subject>Transplants &amp; implants</subject><subject>Urine</subject><subject>Urine - cytology</subject><subject>Wound Healing</subject><subject>X-Ray Microtomography</subject><issn>0363-5465</issn><issn>1552-3365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctLxDAQh4Mouj7uniTgxUt1kjRJe1zqExTBx7lk0-la6SZr0gr-92ZZHyB4CmS--fKbDCGHDE4Z0_oMhBIyV5JDqbjW-QaZMCl5JoSSm2SyKmer-g7ZjfEVAJhWxTbZEYIJlfN8QubT5bLvrBk676hv6XQc_BydHyN9Dp3D7BxD944NfRxwQSvse_r4gjjQC_dinMVIH_xgBh9oNbYtvUbTd25OO0cNrYxLBnrnG-z3yVZr-ogHX-ceebq8eKqus9v7q5tqepvZFHnI2gZLNKLhaMqiYFbM0oVVCJJbAUYZmSbQRVmAhBk0oNGiUMXMcNkAgtgjJ2vtMvi3EeNQL7poU2rjMM1U81xqrmVZyIQe_0Ff_RhcCpcoJTXIkq2EsKZs8DEGbOtl6BYmfNQM6tUO6r87SC1HX-JxtsDmp-H70xOQrYFo5vj76r_CT2L2jPQ</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Chen, Yang</creator><creator>Xu, Yan</creator><creator>Li, Muzhi</creator><creator>Shi, Qiang</creator><creator>Chen, Can</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>202012</creationdate><title>Application of Autogenous Urine-Derived Stem Cell Sheet Enhances Rotator Cuff Healing in a Canine Model</title><author>Chen, Yang ; Xu, Yan ; Li, Muzhi ; Shi, Qiang ; Chen, Can</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-fde9ea3d2ea9881c3bde9c6e052c30a6a51767898050b0d07ece368ba25d0e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Biomechanical Phenomena</topic><topic>Cells, Cultured</topic><topic>Dogs</topic><topic>Male</topic><topic>Rotator cuff</topic><topic>Rotator Cuff - surgery</topic><topic>Rotator Cuff Injuries - surgery</topic><topic>Sports medicine</topic><topic>Stem Cell Transplantation</topic><topic>Stem Cells - cytology</topic><topic>Tomography</topic><topic>Transplants &amp; implants</topic><topic>Urine</topic><topic>Urine - cytology</topic><topic>Wound Healing</topic><topic>X-Ray Microtomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yang</creatorcontrib><creatorcontrib>Xu, Yan</creatorcontrib><creatorcontrib>Li, Muzhi</creatorcontrib><creatorcontrib>Shi, Qiang</creatorcontrib><creatorcontrib>Chen, Can</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 &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; 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>Chen, Yang</au><au>Xu, Yan</au><au>Li, Muzhi</au><au>Shi, Qiang</au><au>Chen, Can</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Application of Autogenous Urine-Derived Stem Cell Sheet Enhances Rotator Cuff Healing in a Canine Model</atitle><jtitle>The American journal of sports medicine</jtitle><addtitle>Am J Sports Med</addtitle><date>2020-12</date><risdate>2020</risdate><volume>48</volume><issue>14</issue><spage>3454</spage><epage>3466</epage><pages>3454-3466</pages><issn>0363-5465</issn><eissn>1552-3365</eissn><abstract>Background: A repaired rotator cuff (RC) often heals with interposed scar tissue, making repairs prone to failure. Urine-derived stem cells (USCs), with robust proliferation ability and multilineage differentiation, can be isolated from urine, avoiding invasive and painful surgical procedures for harvesting the cells. These advantages make it a novel cell source for autologous transplantation to enhance RC healing. Hypothesis: Implantation of an autogenous USC sheet to the injury site will enhance RC healing. Study Design: Controlled laboratory study. Methods: USCs isolated from urine were cultured using ascorbic acid and transforming growth factor β3 to form a cell sheet. Sixteen male mature beagles underwent bilateral shoulder surgery. The right shoulder underwent infraspinatus tendon (IT) insertion detachment and repair only, and the other was subjected to IT insertion detachment and repair, followed by autogenous USC sheet implantation. Among the animals, 3 received a Dil (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate)- labeled USC sheet implant in the right shoulder and were sacrificed at postoperative 6 weeks for cell tracking. The other animals were sacrificed at postoperative 12 weeks, and the IT-humerus complexes were harvested for gross observation, micro–computed tomography evaluation and histological analysis (n = 5), and mechanical testing (n = 8). Additionally, 13 unpaired canine cadaveric shoulders were included as native controls. Results: Micro–computed tomography analysis showed that the USC sheet group had a significant increase in bone volume/total volume and trabecular thickness at the RC healing site when compared with the control group (P &lt; .05 for all). Histologically, the Dil-labeled USC sheet was still visible at the RC healing site, which suggested that the implanted USCs remained viable at postoperative 6 weeks. Meanwhile, the healing interface in the USC sheet group regenerated significantly more enthesis-like tissue than did that of the control group (P &lt; .05). Additionally, the healing interface in the USC sheet group presented a larger fibrocartilage area, more proteoglycan deposition, and higher collagen birefringence than did that of the control group (P &lt; .05 for all). Biomechanically, the USC sheet group showed significantly higher failure load and stiffness versus the control group (P &lt; .05 for all). Conclusion: A USC sheet was able to enhance RC healing in a canine model. Clinical Relevance: The findings of the study showed that USC sheet implantation could serve as a practical application for RC healing.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>33136424</pmid><doi>10.1177/0363546520962774</doi><tpages>13</tpages></addata></record>
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subjects Animals
Biomechanical Phenomena
Cells, Cultured
Dogs
Male
Rotator cuff
Rotator Cuff - surgery
Rotator Cuff Injuries - surgery
Sports medicine
Stem Cell Transplantation
Stem Cells - cytology
Tomography
Transplants & implants
Urine
Urine - cytology
Wound Healing
X-Ray Microtomography
title Application of Autogenous Urine-Derived Stem Cell Sheet Enhances Rotator Cuff Healing in a Canine Model
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