Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx
Objective: Current treatments for vocal fold paralysis are suboptimal in that they fail to restore dynamic function. Autologous muscle stem cell (MSC) therapy is a promising potential therapy for vocal fold paralysis in that it can attenuate denervation‐induced muscle atrophy and provide a vehicle f...
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| Veröffentlicht in: | The Laryngoscope 2008-07, Vol.118 (7), p.1308-1312 |
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| container_title | The Laryngoscope |
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| creator | Halum, Stacey L. Hiatt, Kelly K. Naidu, Moumita Sufyan, Ahmed S. Clapp, D. Wade |
| description | Objective: Current treatments for vocal fold paralysis are suboptimal in that they fail to restore dynamic function. Autologous muscle stem cell (MSC) therapy is a promising potential therapy for vocal fold paralysis in that it can attenuate denervation‐induced muscle atrophy and provide a vehicle for delivery of neurotrophic factors, thereby potentially selectively guiding reinnervation. The goal of this project was to characterize optimal conditions for injected autologous MSC survival in the thyroarytenoid (TA) muscle following recurrent laryngeal nerve (RLN) injury by local administration of adjuvant factors.
Study Design: Animal experiment.
Methods: Unilateral RLN transection and sternocleidomastoid muscle (∼1 g) biopsies were performed in 20 male Wistar rats. One month later, 106 autologous MSCs labeled via retroviral‐enhanced green fluorescent protein (EGFP) transduction were injected into the denervated hemilarynx of each animal with one of four adjuvant therapies: cardiotoxin [(CTX) 10−5 M], insulin‐like growth factor‐1 [(IGF‐ 1) 100 μg/mL], ciliary neurotrophic factor [(CNTF) 50 μg/mL], or saline. Animals were euthanized 1 month later and larynges harvested, sectioned, and analyzed for MSC survival.
Results: All specimens demonstrate extensive MSC survival, with fusion of the MSCs with the denervated myofibers. Based on mean fluorescent intensity of the laryngeal specimens, IGF‐1 and CNTF had the greatest positive influence on MSC survival. Myofiber diameters demonstrated myofiber atrophy to be inversely related to MSC survival, with the least atrophy in the groups having the greatest MSC survival.
Conclusions: Autologous MSC therapy may be a future treatment for vocal fold paralysis. These findings support a model whereby MSCs genetically engineered to secrete CNTF and/or IGF‐1 may not only promote neural regeneration, but also enhance MSC survival in an autocrine fashion. |
| doi_str_mv | 10.1097/MLG.0b013e31816c438e |
| format | Article |
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Study Design: Animal experiment.
Methods: Unilateral RLN transection and sternocleidomastoid muscle (∼1 g) biopsies were performed in 20 male Wistar rats. One month later, 106 autologous MSCs labeled via retroviral‐enhanced green fluorescent protein (EGFP) transduction were injected into the denervated hemilarynx of each animal with one of four adjuvant therapies: cardiotoxin [(CTX) 10−5 M], insulin‐like growth factor‐1 [(IGF‐ 1) 100 μg/mL], ciliary neurotrophic factor [(CNTF) 50 μg/mL], or saline. Animals were euthanized 1 month later and larynges harvested, sectioned, and analyzed for MSC survival.
Results: All specimens demonstrate extensive MSC survival, with fusion of the MSCs with the denervated myofibers. Based on mean fluorescent intensity of the laryngeal specimens, IGF‐1 and CNTF had the greatest positive influence on MSC survival. Myofiber diameters demonstrated myofiber atrophy to be inversely related to MSC survival, with the least atrophy in the groups having the greatest MSC survival.
Conclusions: Autologous MSC therapy may be a future treatment for vocal fold paralysis. These findings support a model whereby MSCs genetically engineered to secrete CNTF and/or IGF‐1 may not only promote neural regeneration, but also enhance MSC survival in an autocrine fashion.</description><identifier>ISSN: 0023-852X</identifier><identifier>EISSN: 1531-4995</identifier><identifier>DOI: 10.1097/MLG.0b013e31816c438e</identifier><identifier>PMID: 18401272</identifier><identifier>CODEN: LARYA8</identifier><language>eng</language><publisher>Hoboken, NJ: John Wiley & Sons, Inc</publisher><subject>Animals ; atrophy ; Biological and medical sciences ; Biopsy ; Cell Survival - physiology ; ciliary-derived neurotrophic factor ; CNTF ; IGF-1 ; Insulin-like growth factor-1 ; laryngeal denervation ; Laryngeal Muscles - cytology ; Laryngeal Muscles - pathology ; laryngeal paralysis ; Medical sciences ; Microscopy, Fluorescence ; Muscle Denervation ; Muscle stem cells ; Muscle, Skeletal - cytology ; Muscular Atrophy - pathology ; myoblasts ; Myoblasts - pathology ; myofiber ; Nerve Regeneration - physiology ; neurotrophic factors ; Otorhinolaryngology. Stomatology ; Rats ; Rats, Wistar ; Recurrent Laryngeal Nerve - pathology ; Recurrent Laryngeal Nerve Injuries ; satellite cell ; Stem Cell Transplantation ; thyroarytenoid muscle ; Transplantation, Autologous ; vocal cord paralysis ; Vocal Cord Paralysis - pathology ; vocal fold paralysis</subject><ispartof>The Laryngoscope, 2008-07, Vol.118 (7), p.1308-1312</ispartof><rights>Copyright © 2008 The Triological Society</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4305-7c20632c9b96ded767a2c7964c6ceeef15334be599050cc9ae17292f5b193dff3</citedby><cites>FETCH-LOGICAL-c4305-7c20632c9b96ded767a2c7964c6ceeef15334be599050cc9ae17292f5b193dff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1097%2FMLG.0b013e31816c438e$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1097%2FMLG.0b013e31816c438e$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27911,27912,45561,45562</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20482103$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18401272$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Halum, Stacey L.</creatorcontrib><creatorcontrib>Hiatt, Kelly K.</creatorcontrib><creatorcontrib>Naidu, Moumita</creatorcontrib><creatorcontrib>Sufyan, Ahmed S.</creatorcontrib><creatorcontrib>Clapp, D. Wade</creatorcontrib><title>Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx</title><title>The Laryngoscope</title><addtitle>The Laryngoscope</addtitle><description>Objective: Current treatments for vocal fold paralysis are suboptimal in that they fail to restore dynamic function. Autologous muscle stem cell (MSC) therapy is a promising potential therapy for vocal fold paralysis in that it can attenuate denervation‐induced muscle atrophy and provide a vehicle for delivery of neurotrophic factors, thereby potentially selectively guiding reinnervation. The goal of this project was to characterize optimal conditions for injected autologous MSC survival in the thyroarytenoid (TA) muscle following recurrent laryngeal nerve (RLN) injury by local administration of adjuvant factors.
Study Design: Animal experiment.
Methods: Unilateral RLN transection and sternocleidomastoid muscle (∼1 g) biopsies were performed in 20 male Wistar rats. One month later, 106 autologous MSCs labeled via retroviral‐enhanced green fluorescent protein (EGFP) transduction were injected into the denervated hemilarynx of each animal with one of four adjuvant therapies: cardiotoxin [(CTX) 10−5 M], insulin‐like growth factor‐1 [(IGF‐ 1) 100 μg/mL], ciliary neurotrophic factor [(CNTF) 50 μg/mL], or saline. Animals were euthanized 1 month later and larynges harvested, sectioned, and analyzed for MSC survival.
Results: All specimens demonstrate extensive MSC survival, with fusion of the MSCs with the denervated myofibers. Based on mean fluorescent intensity of the laryngeal specimens, IGF‐1 and CNTF had the greatest positive influence on MSC survival. Myofiber diameters demonstrated myofiber atrophy to be inversely related to MSC survival, with the least atrophy in the groups having the greatest MSC survival.
Conclusions: Autologous MSC therapy may be a future treatment for vocal fold paralysis. These findings support a model whereby MSCs genetically engineered to secrete CNTF and/or IGF‐1 may not only promote neural regeneration, but also enhance MSC survival in an autocrine fashion.</description><subject>Animals</subject><subject>atrophy</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Cell Survival - physiology</subject><subject>ciliary-derived neurotrophic factor</subject><subject>CNTF</subject><subject>IGF-1</subject><subject>Insulin-like growth factor-1</subject><subject>laryngeal denervation</subject><subject>Laryngeal Muscles - cytology</subject><subject>Laryngeal Muscles - pathology</subject><subject>laryngeal paralysis</subject><subject>Medical sciences</subject><subject>Microscopy, Fluorescence</subject><subject>Muscle Denervation</subject><subject>Muscle stem cells</subject><subject>Muscle, Skeletal - cytology</subject><subject>Muscular Atrophy - pathology</subject><subject>myoblasts</subject><subject>Myoblasts - pathology</subject><subject>myofiber</subject><subject>Nerve Regeneration - physiology</subject><subject>neurotrophic factors</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Recurrent Laryngeal Nerve - pathology</subject><subject>Recurrent Laryngeal Nerve Injuries</subject><subject>satellite cell</subject><subject>Stem Cell Transplantation</subject><subject>thyroarytenoid muscle</subject><subject>Transplantation, Autologous</subject><subject>vocal cord paralysis</subject><subject>Vocal Cord Paralysis - pathology</subject><subject>vocal fold paralysis</subject><issn>0023-852X</issn><issn>1531-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EokvhHyDkC9xSxnYcxze2W7qLlFJBQcDJcpwJGPKx2Mm25ddjtKsiceI0l2cev_OakKcMThho9fKiWp9ADUygYCUrXC5KvEcWTAqW5VrL-2QBwEVWSv75iDyK8TsAU0LCQ3LEyhwYV3xB3l1uJ9_7X3by40DHli7naezGr-Mc6cUcXYf0asKerrDr6NUcdn5nO-oHOn1DeoYDhp2dsKEb7H1nw-1w85g8aG0X8clhHpOP568_rDZZdbl-s1pWWUoKMlOOQyG407UuGmxUoSx3She5KxwitukOkdcotQYJzmmLTHHNW1kzLZq2Fcfkxd67DePPGeNkeh9dimkHTOlNoXkJQhcJzPegC2OMAVuzDb5PWQ0D86dKk6o0_1aZ1p4d_HPdY_N36dBdAp4fABud7dpgB-fjHcchLzkDkbhXe-7ad3j7X4-bavn-i5Q5YyWkL0uKbK_wccKbO4UNP0yhhJLm09u1qfRGnq1OldmI3z1Vnzc</recordid><startdate>200807</startdate><enddate>200807</enddate><creator>Halum, Stacey L.</creator><creator>Hiatt, Kelly K.</creator><creator>Naidu, Moumita</creator><creator>Sufyan, Ahmed S.</creator><creator>Clapp, D. Wade</creator><general>John Wiley & Sons, Inc</general><general>Wiley-Blackwell</general><scope>BSCLL</scope><scope>IQODW</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>200807</creationdate><title>Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx</title><author>Halum, Stacey L. ; Hiatt, Kelly K. ; Naidu, Moumita ; Sufyan, Ahmed S. ; Clapp, D. Wade</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4305-7c20632c9b96ded767a2c7964c6ceeef15334be599050cc9ae17292f5b193dff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>atrophy</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Cell Survival - physiology</topic><topic>ciliary-derived neurotrophic factor</topic><topic>CNTF</topic><topic>IGF-1</topic><topic>Insulin-like growth factor-1</topic><topic>laryngeal denervation</topic><topic>Laryngeal Muscles - cytology</topic><topic>Laryngeal Muscles - pathology</topic><topic>laryngeal paralysis</topic><topic>Medical sciences</topic><topic>Microscopy, Fluorescence</topic><topic>Muscle Denervation</topic><topic>Muscle stem cells</topic><topic>Muscle, Skeletal - cytology</topic><topic>Muscular Atrophy - pathology</topic><topic>myoblasts</topic><topic>Myoblasts - pathology</topic><topic>myofiber</topic><topic>Nerve Regeneration - physiology</topic><topic>neurotrophic factors</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Recurrent Laryngeal Nerve - pathology</topic><topic>Recurrent Laryngeal Nerve Injuries</topic><topic>satellite cell</topic><topic>Stem Cell Transplantation</topic><topic>thyroarytenoid muscle</topic><topic>Transplantation, Autologous</topic><topic>vocal cord paralysis</topic><topic>Vocal Cord Paralysis - pathology</topic><topic>vocal fold paralysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Halum, Stacey L.</creatorcontrib><creatorcontrib>Hiatt, Kelly K.</creatorcontrib><creatorcontrib>Naidu, Moumita</creatorcontrib><creatorcontrib>Sufyan, Ahmed S.</creatorcontrib><creatorcontrib>Clapp, D. Wade</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</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>The Laryngoscope</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Halum, Stacey L.</au><au>Hiatt, Kelly K.</au><au>Naidu, Moumita</au><au>Sufyan, Ahmed S.</au><au>Clapp, D. Wade</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx</atitle><jtitle>The Laryngoscope</jtitle><addtitle>The Laryngoscope</addtitle><date>2008-07</date><risdate>2008</risdate><volume>118</volume><issue>7</issue><spage>1308</spage><epage>1312</epage><pages>1308-1312</pages><issn>0023-852X</issn><eissn>1531-4995</eissn><coden>LARYA8</coden><abstract>Objective: Current treatments for vocal fold paralysis are suboptimal in that they fail to restore dynamic function. Autologous muscle stem cell (MSC) therapy is a promising potential therapy for vocal fold paralysis in that it can attenuate denervation‐induced muscle atrophy and provide a vehicle for delivery of neurotrophic factors, thereby potentially selectively guiding reinnervation. The goal of this project was to characterize optimal conditions for injected autologous MSC survival in the thyroarytenoid (TA) muscle following recurrent laryngeal nerve (RLN) injury by local administration of adjuvant factors.
Study Design: Animal experiment.
Methods: Unilateral RLN transection and sternocleidomastoid muscle (∼1 g) biopsies were performed in 20 male Wistar rats. One month later, 106 autologous MSCs labeled via retroviral‐enhanced green fluorescent protein (EGFP) transduction were injected into the denervated hemilarynx of each animal with one of four adjuvant therapies: cardiotoxin [(CTX) 10−5 M], insulin‐like growth factor‐1 [(IGF‐ 1) 100 μg/mL], ciliary neurotrophic factor [(CNTF) 50 μg/mL], or saline. Animals were euthanized 1 month later and larynges harvested, sectioned, and analyzed for MSC survival.
Results: All specimens demonstrate extensive MSC survival, with fusion of the MSCs with the denervated myofibers. Based on mean fluorescent intensity of the laryngeal specimens, IGF‐1 and CNTF had the greatest positive influence on MSC survival. Myofiber diameters demonstrated myofiber atrophy to be inversely related to MSC survival, with the least atrophy in the groups having the greatest MSC survival.
Conclusions: Autologous MSC therapy may be a future treatment for vocal fold paralysis. These findings support a model whereby MSCs genetically engineered to secrete CNTF and/or IGF‐1 may not only promote neural regeneration, but also enhance MSC survival in an autocrine fashion.</abstract><cop>Hoboken, NJ</cop><pub>John Wiley & Sons, Inc</pub><pmid>18401272</pmid><doi>10.1097/MLG.0b013e31816c438e</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals atrophy Biological and medical sciences Biopsy Cell Survival - physiology ciliary-derived neurotrophic factor CNTF IGF-1 Insulin-like growth factor-1 laryngeal denervation Laryngeal Muscles - cytology Laryngeal Muscles - pathology laryngeal paralysis Medical sciences Microscopy, Fluorescence Muscle Denervation Muscle stem cells Muscle, Skeletal - cytology Muscular Atrophy - pathology myoblasts Myoblasts - pathology myofiber Nerve Regeneration - physiology neurotrophic factors Otorhinolaryngology. Stomatology Rats Rats, Wistar Recurrent Laryngeal Nerve - pathology Recurrent Laryngeal Nerve Injuries satellite cell Stem Cell Transplantation thyroarytenoid muscle Transplantation, Autologous vocal cord paralysis Vocal Cord Paralysis - pathology vocal fold paralysis |
| title | Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx |
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