Optimization of autologous muscle stem cell survival in the denervated hemilarynx

Stacey L. Halum, Kelly K. Hiatt, Moumita Naidu, Ahmed S. Sufyan, D. Clapp

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 Wis tar rats. One month later, 106 autologous MSCs labeled via retro viral-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], insulinlike 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.

Original languageEnglish
Pages (from-to)1308-1312
Number of pages5
JournalLaryngoscope
Volume118
Issue number7
DOIs
StatePublished - Jul 2008

Fingerprint

Muscle Cells
Cell Survival
Stem Cells
Ciliary Neurotrophic Factor
Vocal Cords
Recurrent Laryngeal Nerve Injuries
Paralysis
Cell- and Tissue-Based Therapy
Insulin-Like Growth Factor I
Atrophy
Cardiotoxins
Laryngeal Muscles
Tars
Muscular Atrophy
Nerve Growth Factors
Denervation
Therapeutics
Larynx
Regeneration
Intercellular Signaling Peptides and Proteins

Keywords

  • Atrophy
  • Ciliary-derived neurotrophic factor
  • CNTF
  • IGF-1
  • Insulin-like growth factor-1
  • Laryngeal denervation
  • Laryngeal paralysis
  • Muscle stem cells
  • Myoblasts
  • Myofiber
  • Neurotrophic factors
  • Satellite cell
  • Vocal cord paralysis
  • Vocal fold paralysis

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Medicine(all)

Cite this

Optimization of autologous muscle stem cell survival in the denervated hemilarynx. / Halum, Stacey L.; Hiatt, Kelly K.; Naidu, Moumita; Sufyan, Ahmed S.; Clapp, D.

In: Laryngoscope, Vol. 118, No. 7, 07.2008, p. 1308-1312.

Research output: Contribution to journalArticle

Halum, Stacey L. ; Hiatt, Kelly K. ; Naidu, Moumita ; Sufyan, Ahmed S. ; Clapp, D. / Optimization of autologous muscle stem cell survival in the denervated hemilarynx. In: Laryngoscope. 2008 ; Vol. 118, No. 7. pp. 1308-1312.
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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 Wis tar rats. One month later, 106 autologous MSCs labeled via retro viral-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], insulinlike 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.",
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N2 - 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 Wis tar rats. One month later, 106 autologous MSCs labeled via retro viral-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], insulinlike 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.

AB - 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 Wis tar rats. One month later, 106 autologous MSCs labeled via retro viral-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], insulinlike 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.

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KW - Muscle stem cells

KW - Myoblasts

KW - Myofiber

KW - Neurotrophic factors

KW - Satellite cell

KW - Vocal cord paralysis

KW - Vocal fold paralysis

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