Prevention and treatment of vocal fold scarring and atrophy remain challenging. The aim of this study was to treat injured vocal folds using autologous adipose tissue-derived stromal cells (ADSCs) and evaluate the ability to prevent vocal fold scarring and atrophy by ADSCs in a canine animal model. Ten adult dogs were used for this experiment. ADSCs from the adipose tissue from the inguinal area were isolated and cultured in all dogs. Immediately after being mixed with atelocollagen, the ADSCs (1–3 × 106) were injected into the right vocal fold of each animal, using a syringe with a 23-gauge needle. As a control, atelocollagen was injected into the left vocal fold of the same dog. The effects of the prevention of vocal fold scarring and atrophy were measured by morphological and histological assessment. At 8 weeks, there was a difference in granuloma and atrophic changes between the ADSC-injected and control sides in the majority of the dogs. This difference continued to be present at the 24 weeks’ follow-up. On histopathologic examination, a large number of cells labeled with a fluorochrome were observed in ADSC-injected vocal folds 8 weeks after the initial treatment. This study demonstrates the multipotential ability of ADSCs in the regeneration of injured vocal folds. Injecting ADSCs into a damaged vocal fold appears to be useful in preventing vocal fold scarring and atrophy 24 weeks after initial damage.

1.
Arsenijevic, Y., S. Weiss, B. Schneider, P. Aebischer (2001) Insulin-like growth factor-I is necessary for neural stem cell proliferation and demonstrates distinct actions of epidermal growth factor and fibroblast growth factor-2. J Neurosci 21: 7194–7202.
2.
Beck, P.L., D.K. Podolsky (1999) Growth factors in inflammatory bowel disease. Inflamm Bowel Dis 5: 44–60.
3.
Brzozowski, T., P.C. Konturek, S.J. Konturek, D. Schuppan, D. Drozdowicz, S. Kwiecien, J. Majka, T. Nakamura, E. Hahn (2001) Effect of local application of growth factors on gastric ulcer healing and mucosal expression of cyclooxygenase-1 and -2. Digestion 64: 15–29.
4.
Chan, R.W., I.R. Titze (1998) Viscosities of implantable biomaterials in vocal fold augmentation surgery. Laryngoscope 108: 725–731.
5.
Chan, R.W., I.R. Titze (1999) Hyaluronic acid (with fibronectin) as a bioimplant for the vocal fold mucosa. Laryngoscope 109: 1142–1149.
6.
Chhetri, D.K., C. Head, E. Revazova, S. Hart, S. Bhuta, G.S. Berke (2004) Lamina propria replacement therapy with cultured autologous fibroblasts for vocal fold scars. Otolaryngol Head Neck Surg 131: 864–870.
7.
De Ugarte, D.A., K. Morizono, A. Elbarbary, Z. Alfonso, P.A. Zuk, M. Zuh, J.L. Dragoo, P. Ashjian, B. Thomas, P. Benhaim, I. Chen, J. Fraser, M.H. Hedrick (2003) Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 174: 101–109.
8.
Dezawa, M., I. Takahashi, M. Esaki, M. Takano, H. Sawada (2001) Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur J Neurosci 14: 1771–1776.
9.
Ford, C.N., P.A. Staskowski, D.M. Bless (1995) Autologous collagen vocal cord injection: a preliminary clinical study. Laryngoscope 105: 944–948.
10.
Hallen, L., A. Dahlqvist, C. Laurent (1998) Dextranomeres in hyaluronan (DiHA): a promising substance in treating vocal cord insufficiency. Laryngoscope 108: 393–397.
11.
Herrera, M.B., B. Bussolati, S. Bruno, V. Fonsato, G.M. Romanazzi, G. Camussi (2004) Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med 14: 1035–1041.
12.
Hertegard, S., L. Hallen, C. Laurent, E. Lindstrom, K. Olofsson, P. Testad, A. Dahlqvist (2004) Cross-linked hyaluronan versus collagen for injection treatment of glottal insufficiency: 2-year follow-up. Acta Otolaryngol 124: 1208–1214.
13.
Hill, D.P., A.D. Meyers, J. Harris (1991) Autologous fat injection for vocal cord medialization in the canine larynx. Laryngoscope 101: 344–348.
14.
Hirano, S., D.M. Bless, B. Rousseau, N. Welham, D. Montequin, R.W. Chan, C.N. Ford (2004) Prevention of vocal fold scarring by topical injection of hepatocyte growth factor in a rabbit model. Laryngoscope 114: 548–556.
15.
Horwitz, E.M., D.J. Prockop, L.A. Fitzpatrick, W.W. Koo, P.L. Gordon, M. Neel, M. Sussman, P. Orchard, J.C. Marx, R.E. Pyeritz, M.K. Brenner (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5: 309–313.
16.
Isshiki, N., H. Okamura, T. Ishikawa (1975) Thyroplasty type I: lateral compression for dysphonia due to vocal cord paralysis or atrophy. Acta Otolaryngol (Stockh) 80: 465– 473.
17.
Kanemaru, S.I., T. Nakamura, K. Omori, H. Kojima, A. Magrufov, Y. Hiratsuka, S. Hirano, J. Ito, Y. Shimizu (2003) Regeneration of the vocal fold using autologous mesenchymal stem cells. Ann Otol Rhinol Laryngol 112: 915–920.
18.
Lee, R.H., B. Kim, I.S. Choi, H. Kim, H.S. Choi, K.T. Suh, Y.C. Bae, J.S. Jung (2004) Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem 14: 311–324.
19.
Matsumoto, K., T. Nakamura (1997) Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration. Biochem Biophys Res Commun 239: 639–644.
20.
Pittenger, M.F., A.M. Mackay, S.C. Beck, R.K. Jaiswal, R. Douglas, J.D. Mosca, M.A. Moorman, D.W. Simonetti, S. Craig , D.R. Marshak (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–147.
21.
Pittenger, M., P. Vanguri, D. Simonetti, R. Young (2002) Adult mesenchymal stem cells: potential for muscle and tendon regeneration and use in gene therapy. J Musculoskelet Neuronal Interact 2: 309–320.
22.
Rihkanen, H. (1998) Vocal fold augmentation by injection of autologous fascia. Laryngoscope 108: 51–54.
23.
Tang, Y.L., Q. Zhao, X. Qin, L. Shen, L. Cheng, J. Ge, M.I. Phillips (2005) Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann Thorac Surg 80: 229–236.
24.
Young, H.E., T.A. Steele, R.A. Bray, J. Hudson, J.A. Floyd, K. Hawkins, K. Thomas, T. Austin, C. Edwards, J. Cuzzourt, M. Duenzl, P.A. Lucas, A.C. Black (2001) Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec 264: 51–62.
25.
Wexler, D.B., J. Jiang, S.D. Gray, I.R. Titze (1989) Phonosurgical studies: fat-graft reconstruction of injured canine vocal cords. Ann Otol Rhinol Laryngol 98: 668–673.
26.
Zuk, P.A., M. Zhu, H. Mizuno, J. Huang, J.W. Futrell, A.J. Katz, P. Benhaim, H.P. Rorenz, M.H. Hedrick (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7: 211–228.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.