Injection of autologous muscle stem cells (myoblasts) for the treatment of vocal fold paralysis: A pilot study

Stacey L. Halum, Moumita Naidu, Dawn M. Delo, Anthony Atala, Cynthia M. Hingtgen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

OBJECTIVE: Autologous muscle stem cell (myoblast) therapy may be an ideal treatment for vocal fold paralysis because of its technical ease (administered by injection), its potential to restore muscular defects and dynamic function, and its autologous origin. The goal of this project was to determine whether autologous myoblast injection into the thyroarytenoid (TA) muscle after recurrent laryngeal nerve (RLN) injury could attenuate TA muscle atrophy and enhance spontaneous reinnervation. STUDY DESIGN: This was an animal experiment. METHODS: Unilateral RLN transection and sternocleidomastoid muscle (approximately 1 g) biopsies were performed in 16 male Wistar rats. Biopsies were used to create myoblast cultures for each animal. One month later, 10 autologous myoblasts labeled with fluorescent cell membrane marker (PKH26) were injected into the denervated TA of each study animal, with saline injected into controls. Animals were euthanized at 2 weeks and 2 months after myoblast injection. Outcomes included myoblast survival, TA fiber diameter and volume, and reinnervation status (motor endplate to nerve contact staining). RESULTS: All denervated TA study specimens demonstrated viable myoblasts under fluorescent microscopy, with the myoblasts demonstrating fusion with the TA myofibers at 2 months. The myoblast-treated group had greater mean TA fiber diameter than denervated TA controls at 2 months (25.1 vs. 21.1 μm; P = .04) but not at 2 weeks (25.7 μm vs. 23.5 μm; P = .06). Mean TA volumes were greater in the myoblast-treated groups at both time points. Two of the animals in the myoblast-treated group demonstrated adductor motion at 2 months, whereas none of the 2 week study animals or controls recovered adduction. Reinnervation was not significantly different between the myoblast-treated groups and the denervated controls. CONCLUSIONS: Autologous myoblast therapy may be a future treatment for vocal fold paralysis, with current findings demonstrating myoblast survival with attenuation of TA muscle atrophy.

Original languageEnglish
Pages (from-to)917-922
Number of pages6
JournalLaryngoscope
Volume117
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Vocal Cords
Myoblasts
Paralysis
Muscle Cells
Stem Cells
Injections
Laryngeal Muscles
Therapeutics
Recurrent Laryngeal Nerve Injuries
Muscular Atrophy
Motor Endplate
Biopsy
Cell- and Tissue-Based Therapy
Wistar Rats
Microscopy

Keywords

  • Laryngeal denervation
  • Laryngeal paralysis
  • Muscle stem cells
  • Myoblasts
  • Myofibers
  • Satellite cells
  • Stem cells
  • Vocal cord paralysis
  • Vocal fold paralysis

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Injection of autologous muscle stem cells (myoblasts) for the treatment of vocal fold paralysis : A pilot study. / Halum, Stacey L.; Naidu, Moumita; Delo, Dawn M.; Atala, Anthony; Hingtgen, Cynthia M.

In: Laryngoscope, Vol. 117, No. 5, 01.05.2007, p. 917-922.

Research output: Contribution to journalArticle

Halum, Stacey L. ; Naidu, Moumita ; Delo, Dawn M. ; Atala, Anthony ; Hingtgen, Cynthia M. / Injection of autologous muscle stem cells (myoblasts) for the treatment of vocal fold paralysis : A pilot study. In: Laryngoscope. 2007 ; Vol. 117, No. 5. pp. 917-922.
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abstract = "OBJECTIVE: Autologous muscle stem cell (myoblast) therapy may be an ideal treatment for vocal fold paralysis because of its technical ease (administered by injection), its potential to restore muscular defects and dynamic function, and its autologous origin. The goal of this project was to determine whether autologous myoblast injection into the thyroarytenoid (TA) muscle after recurrent laryngeal nerve (RLN) injury could attenuate TA muscle atrophy and enhance spontaneous reinnervation. STUDY DESIGN: This was an animal experiment. METHODS: Unilateral RLN transection and sternocleidomastoid muscle (approximately 1 g) biopsies were performed in 16 male Wistar rats. Biopsies were used to create myoblast cultures for each animal. One month later, 10 autologous myoblasts labeled with fluorescent cell membrane marker (PKH26) were injected into the denervated TA of each study animal, with saline injected into controls. Animals were euthanized at 2 weeks and 2 months after myoblast injection. Outcomes included myoblast survival, TA fiber diameter and volume, and reinnervation status (motor endplate to nerve contact staining). RESULTS: All denervated TA study specimens demonstrated viable myoblasts under fluorescent microscopy, with the myoblasts demonstrating fusion with the TA myofibers at 2 months. The myoblast-treated group had greater mean TA fiber diameter than denervated TA controls at 2 months (25.1 vs. 21.1 μm; P = .04) but not at 2 weeks (25.7 μm vs. 23.5 μm; P = .06). Mean TA volumes were greater in the myoblast-treated groups at both time points. Two of the animals in the myoblast-treated group demonstrated adductor motion at 2 months, whereas none of the 2 week study animals or controls recovered adduction. Reinnervation was not significantly different between the myoblast-treated groups and the denervated controls. CONCLUSIONS: Autologous myoblast therapy may be a future treatment for vocal fold paralysis, with current findings demonstrating myoblast survival with attenuation of TA muscle atrophy.",
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AU - Halum, Stacey L.

AU - Naidu, Moumita

AU - Delo, Dawn M.

AU - Atala, Anthony

AU - Hingtgen, Cynthia M.

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AB - OBJECTIVE: Autologous muscle stem cell (myoblast) therapy may be an ideal treatment for vocal fold paralysis because of its technical ease (administered by injection), its potential to restore muscular defects and dynamic function, and its autologous origin. The goal of this project was to determine whether autologous myoblast injection into the thyroarytenoid (TA) muscle after recurrent laryngeal nerve (RLN) injury could attenuate TA muscle atrophy and enhance spontaneous reinnervation. STUDY DESIGN: This was an animal experiment. METHODS: Unilateral RLN transection and sternocleidomastoid muscle (approximately 1 g) biopsies were performed in 16 male Wistar rats. Biopsies were used to create myoblast cultures for each animal. One month later, 10 autologous myoblasts labeled with fluorescent cell membrane marker (PKH26) were injected into the denervated TA of each study animal, with saline injected into controls. Animals were euthanized at 2 weeks and 2 months after myoblast injection. Outcomes included myoblast survival, TA fiber diameter and volume, and reinnervation status (motor endplate to nerve contact staining). RESULTS: All denervated TA study specimens demonstrated viable myoblasts under fluorescent microscopy, with the myoblasts demonstrating fusion with the TA myofibers at 2 months. The myoblast-treated group had greater mean TA fiber diameter than denervated TA controls at 2 months (25.1 vs. 21.1 μm; P = .04) but not at 2 weeks (25.7 μm vs. 23.5 μm; P = .06). Mean TA volumes were greater in the myoblast-treated groups at both time points. Two of the animals in the myoblast-treated group demonstrated adductor motion at 2 months, whereas none of the 2 week study animals or controls recovered adduction. Reinnervation was not significantly different between the myoblast-treated groups and the denervated controls. CONCLUSIONS: Autologous myoblast therapy may be a future treatment for vocal fold paralysis, with current findings demonstrating myoblast survival with attenuation of TA muscle atrophy.

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KW - Myofibers

KW - Satellite cells

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KW - Vocal cord paralysis

KW - Vocal fold paralysis

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