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Efficacy and Safety of Autologous Stromal Vascular Fraction in the Treatment of Empty Nose Syndrome

  • Kim, Do-Youn (Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Hong, Hye Ran (Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Choi, Eun Wook (Prostemics Research Institute) ;
  • Yoon, Sang Won (Prostemics Research Institute) ;
  • Jang, Yong Ju (Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2017.11.24
  • Accepted : 2018.03.29
  • Published : 2018.12.31

Abstract

Objectives. Regenerative treatment using stem cells may serve as treatment option for empty nose syndrome (ENS), which is caused by the lack of turbinate tissue and deranged nervous system in the nasal cavity. We aimed to assess the efficacy and safety of the autologous stromal vascular fraction (SVF) in the treatment of ENS. Methods. In this prospective observational clinical study, we enrolled 10 ENS patients who volunteered to undergo treatment of ENS through the injection of autologous SVF. Data, including demographic data, pre- and postoperative Sino-Nasal Outcome Test-25 (SNOT-25) scores, overall patient satisfaction, and postoperative complications, were prospectively collected. Nasal secretion was assessed using the polyurethane foam absorption method, and the levels of biological markers were analyzed in both ENS group and control group using enzyme-linked immunosorbent assay. The SVF extracted from abdominal fat was diluted and injected into both inferior turbinates. Results. Among the 10 initial patients, one was excluded from the study. Subjective satisfaction was rated as "much improved" in two and "no change" in seven. Among the improved patients, the mean preinjection SNOT-25 score was 55.0 and the score at 6 months after injection was 19.5. However, the average SNOT-25 score of nine participants at 6 months after injection (mean${\pm}$standard deviation, $62.4{\pm}35.8$) did not differ significantly from the baseline SNOT-25 score ($70.1{\pm}24.7$, P>0.05, respectively). Among the various inflammatory markers assessed, the levels of interleukin $(IL)-1{\beta}$, IL-8, and calcitonin gene-related peptide were significantly higher in ENS patients. Compared with preinjection secretion level, the nasal secretions from SVF-treated patients showed decreased expressions of $IL-1{\beta}$ and IL-8 after injection. Conclusion. Although SVF treatment appears to decrease the inflammatory cytokine levels in the nasal mucosa, a single SVF injection was not effective in terms of symptom improvement and patient satisfaction. Further trials are needed to identify a more practical and useful regenerative treatment modality for patients with ENS.

Keywords

Acknowledgement

Supported by : Prostemics Co., LTD.

References

  1. Oluwole M, Mills RP. An audit of the early complications of turbinectomy. Ann R Coll Surg Engl. 1994 Sep;76(5):339-41.
  2. Houser SM. Surgical treatment for empty nose syndrome. Arch Otolaryngol Head Neck Surg. 2007 Sep;133(9):858-63. https://doi.org/10.1001/archotol.133.9.858
  3. Houser SM. Empty nose syndrome associated with middle turbinate resection. Otolaryngol Head Neck Surg. 2006 Dec;135(6):972-3. https://doi.org/10.1016/j.otohns.2005.04.017
  4. Kuan EC, Suh JD, Wang MB. Empty nose syndrome. Curr Allergy Asthma Rep. 2015 Jan;15(1):493. https://doi.org/10.1007/s11882-014-0493-x
  5. Shah K, Guarderas J, Krishnaswamy G. Empty nose syndrome and atrophic rhinitis. Ann Allergy Asthma Immunol. 2016 Sep;117(3): 217-20. https://doi.org/10.1016/j.anai.2016.07.006
  6. Jung JH, Baguindali MA, Park JT, Jang YJ. Costal cartilage is a superior implant material than conchal cartilage in the treatment of empty nose syndrome. Otolaryngol Head Neck Surg. 2013 Sep;149(3): 500-5. https://doi.org/10.1177/0194599813491223
  7. Modrzynski M. Hyaluronic acid gel in the treatment of empty nose syndrome. Am J Rhinol Allergy. 2011 Mar-Apr;25(2):103-6. https://doi.org/10.2500/ajra.2011.25.3577
  8. Saafan ME. Acellular dermal (alloderm) grafts versus silastic sheets implants for management of empty nose syndrome. Eur Arch Otorhinolaryngol. 2013 Feb;270(2):527-33. https://doi.org/10.1007/s00405-012-1955-1
  9. Leong SC. The clinical efficacy of surgical interventions for empty nose syndrome: a systematic review. Laryngoscope. 2015 Jul;125(7): 1557-62. https://doi.org/10.1002/lary.25170
  10. Coste A, Dessi P, Serrano E. Empty nose syndrome. Eur Ann Otorhinolaryngol Head Neck Dis. 2012 Apr;129(2):93-7. https://doi.org/10.1016/j.anorl.2012.02.001
  11. Dayal A, Rhee JS, Garcia GJ. Impact of middle versus inferior total turbinectomy on nasal aerodynamics. Otolaryngol Head Neck Surg. 2016 Sep;155(3):518-25. https://doi.org/10.1177/0194599816644915
  12. Kang SK, Shin MJ, Jung JS, Kim YG, Kim CH. Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury. Stem Cells Dev. 2006 Aug;15(4):583-94. https://doi.org/10.1089/scd.2006.15.583
  13. Kim DY, Ji YH, Kim DW, Dhong ES, Yoon ES. Effects of platelet-rich plasma, adipose-derived stem cells, and stromal vascular fraction on the survival of human transplanted adipose tissue. J Korean Med Sci. 2014 Nov;29 Suppl 3:S193-200. https://doi.org/10.3346/jkms.2014.29.S3.S193
  14. Lataillade JJ, Doucet C, Bey E, Carsin H, Huet C, Clairand I, et al. New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy. Regen Med. 2007 Sep;2(5):785-94. https://doi.org/10.2217/17460751.2.5.785
  15. Premaratne GU, Ma LP, Fujita M, Lin X, Bollano E, Fu M. Stromal vascular fraction transplantation as an alternative therapy for ischemic heart failure: anti-inflammatory role. J Cardiothorac Surg. 2011 Mar;6:43. https://doi.org/10.1186/1749-8090-6-43
  16. Rodriguez JP, Murphy MP, Hong S, Madrigal M, March KL, Minev B, et al. Autologous stromal vascular fraction therapy for rheumatoid arthritis: rationale and clinical safety. Int Arch Med. 2012 Feb;5:5. https://doi.org/10.1186/1755-7682-5-5
  17. Thamboo A, Velasquez N, Habib AR, Zarabanda D, Paknezhad H, Nayak JV. Defining surgical criteria for empty nose syndrome: validation of the office-based cotton test and clinical interpretability of the validated Empty Nose Syndrome 6-Item Questionnaire. Laryngoscope. 2017 Aug;127(8):1746-52. https://doi.org/10.1002/lary.26549
  18. Jang YJ, Kim JH, Song HY. Empty nose syndrome: radiologic findings and treatment outcomes of endonasal microplasty using cartilage implants. Laryngoscope. 2011 Jun;121(6):1308-12. https://doi.org/10.1002/lary.21734
  19. Riechelmann H, Deutschle T, Friemel E, Gross HJ, Bachem M. Biological markers in nasal secretions. Eur Respir J. 2003 Apr;21(4): 600-5. https://doi.org/10.1183/09031936.03.00072003
  20. Jiang C, Wong F, Chen K, Shi R. Assessment of surgical results in patients with empty nose syndrome using the 25-item Sino-Nasal Outcome Test Evaluation. JAMA Otolaryngol Head Neck Surg. 2014 May;140(5):453-8. https://doi.org/10.1001/jamaoto.2014.84
  21. Palumbo P, Miconi G, Cinque B, La Torre C, Lombardi F, Zoccali G, et al. In vitro evaluation of different methods of handling human liposuction aspirate and their effect on adipocytes and adipose derived stem cells. J Cell Physiol. 2015 Aug;230(8):1974-81. https://doi.org/10.1002/jcp.24965
  22. Phipps KD, Gebremeskel S, Gillis J, Hong P, Johnston B, Bezuhly M. Alternatively activated M2 macrophages improve autologous fat graft survival in a mouse model through induction of angiogenesis. Plast Reconstr Surg. 2015 Jan;135(1):140-9.
  23. Xu X, Li L, Wang C, Liu Y, Chen C, Yan J, et al. The expansion of autologous adipose-derived stem cells in vitro for the functional reconstruction of nasal mucosal tissue. Cell Biosci. 2015 Sep;5:54. https://doi.org/10.1186/s13578-015-0045-7
  24. Friji MT, Gopalakrishnan S, Verma SK, Parida PK, Mohapatra DP. New regenerative approach to atrophic rhinitis using autologous lipoaspirate transfer and platelet-rich plasma in five patients: our experience. Clin Otolaryngol. 2014 Oct;39(5):289-92. https://doi.org/10.1111/coa.12269
  25. Tan SS, Loh W. The utility of adipose-derived stem cells and stromal vascular fraction for oncologic soft tissue reconstruction: is it safe? A matter for debate. Surgeon. 2017 Aug;15(4):186-9. https://doi.org/10.1016/j.surge.2016.09.010
  26. Scheithauer MO. Surgery of the turbinates and “empty nose” syndrome. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2010;9: Doc03.
  27. Tomassen P, Vandeplas G, Van Zele T, Cardell LO, Arebro J, Olze H, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016 May; 137(5):1449-56.e4. https://doi.org/10.1016/j.jaci.2015.12.1324
  28. Luo Q, Zhang Z, Liu D, Feng K, Jin X, Zhang J. Human neutrophil elastase induces MUC5AC overexpression in chronic rhinosinusitis through tumour necrosis factor-alpha converting enzyme. Acta Otolaryngol. 2016 Jun;136(6):641-8. https://doi.org/10.3109/00016489.2016.1144145
  29. Raphael GD, Jeney EV, Baraniuk JN, Kim I, Meredith SD, Kaliner MA. Pathophysiology of rhinitis: lactoferrin and lysozyme in nasal secretions. J Clin Invest. 1989 Nov;84(5):1528-35. https://doi.org/10.1172/JCI114329
  30. Hauser-Kronberger C, Hacker GW, Franz P, Albegger K, Dietze O. CGRP and substance P in intraepithelial neuronal structures of the human upper respiratory system. Regul Pept. 1997 Oct;72(2-3):79-85. https://doi.org/10.1016/S0167-0115(97)01040-9

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