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Regeneration of emphysematous lungs using gelatin sheets that release basic fibroblast growth factor

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Abstract

Purpose

Basic fibroblast growth factor (bFGF) induces regeneration and neovascularization of the lungs. We conducted this study to demonstrate the regeneration of emphysematous lungs achieved by gelatin sheets that slowly release bFGF into the visceral pleura in a canine model.

Methods

Porcine pancreatic elastase was used to induce bilateral lower lobe pulmonary emphysema in dogs. Slow-release bFGF gelatin sheets were attached to the visceral pleura of the left lower lobe via thoracotomy. The subjects were divided into two groups: one treated with gelatin sheets containing slow-release bFGF (bFGF+ group, n = 5), and the other, treated with only gelatin sheets (bFGF− group, n = 5). The subjects were euthanized after 28 days and histologic lung assessment was performed. The results were evaluated in terms of the mean linear intercept (MLI) and microvessel count.

Results

The MLI was significantly shorter in the bFGF+ group than in the bFGF− group; (110.0 ± 24.38 vs. 208.9 ± 33.08 μm; P = 0.0006). The microvessel count was not significantly different between the bFGF+ and bFGF− groups (12.20 ± 3.007 vs. 5.35 ± 2.3425; P = 0.075); however, it was significantly higher in the bFGF-attached lungs than in the emphysema group (12.20 ± 3.007 vs. 4.57 ± 0.8896; P = 0.012).

Conclusions

Attaching gelatin sheets with slow-release bFGF to the visceral pleura induced lung regeneration and vascularization in a canine pulmonary emphysema model.

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References

  1. World Health Organization. The top 10 causes of death. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death (October 3, 2021 date last Accessed).

  2. Young KA, Dilling DF. The future of lung transplantation. Chest. 2019;155:465–73.

    Article  Google Scholar 

  3. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003;348:2059–73.

    Article  Google Scholar 

  4. Ciccone AM, Meyers BF, Guthrie TJ, Davis GE, Yusen RD, Lefrak SS, et al. Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema. J Thorac Cardiovasc Surg. 2003;125:513–25.

    Article  Google Scholar 

  5. Yusen RD, Lefrak SS, Gierada DS, Davis GE, Meyers BF, Patterson GA, et al. A prospective evaluation of lung volume reduction surgery in 200 consecutive patients. Chest. 2003;123:1026–37.

    Article  Google Scholar 

  6. Stolk J, Stockley RA, Stoel BC, Cooper BG, Piitulainen E, Seersholm N, et al. Randomised controlled trial for emphysema with a selective agonist of the gamma-type retinoic acid receptor. Eur Respir J. 2012;40:306–12.

    Article  CAS  Google Scholar 

  7. Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest. 2013;143:1590–8.

    Article  CAS  Google Scholar 

  8. Bikfalvi A, Klein S, Pintucci G, Rifkin DB. Biological roles of fibroblast growth factor-2. Endocr Rev. 1997;18:26–45.

    CAS  PubMed  Google Scholar 

  9. Evans MJ, Fanucchi MV, Van Winkle LS, Baker GL, Murphy AE, Nishio SJ, et al. Fibroblast growth factor-2 during postnatal development of the tracheal basement membrane zone. Am J Physiol Lung Cell Mol Physiol. 2002;283:L1263–70.

    Article  CAS  Google Scholar 

  10. Kawago M, Yoshimasu T, Tabata Y, Yamamoto M, Hirai Y, Kinoshita T, et al. Intrapleural administration of gelatin-embedded, sustained-release basic fibroblast growth factor for the regeneration of emphysematous lungs in rats. J Thorac Cardiovasc Surg. 2014;147:1644–9.

    Article  CAS  Google Scholar 

  11. Kim YS, Hong G, Kim DH, Kim YM, Kim YK, Oh YM, et al. The role of FGF-2 in smoke-induced emphysema and the therapeutic potential of recombinant FGF-2 in patients with COPD. Exp Mol Med. 2018;50:150.

    PubMed Central  Google Scholar 

  12. Igai H, Chang SS, Gotoh M, Yamamoto Y, Yamamoto M, Tabata Y, et al. Tracheal cartilage regeneration and new bone formation by slow release of bone morphogenetic protein (BMP)-2. ASAIO J. 2008;54:104–8.

    Article  CAS  Google Scholar 

  13. Okamoto T, Yamamoto Y, Gotoh M, Huang CL, Nakamura T, Shimizu Y, et al. Slow release of bone morphogenetic protein 2 from a gelatin sponge to promote regeneration of tracheal cartilage in a canine model. J Thorac Cardiovasc Surg. 2004;127:329–34.

    Article  CAS  Google Scholar 

  14. Igai H, Yamamoto Y, Chang SS, Yamamoto M, Tabata Y, Yokomise H. Tracheal cartilage regeneration by slow release of basic fibroblast growth factor from a gelatin sponge. J Thorac Cardiovasc Surg. 2007;134:170–5.

    Article  Google Scholar 

  15. Misaki N, Yamamoto Y, Okamoto T, Chang SS, Igai H, Gotoh M, et al. Intra-thoracic fibrous tissue induction by polylactic acid and epsilon-caprolactone copolymer cubes, with or without slow release of basic fibroblast growth factor. Eur J Cardiothorac Surg. 2007;32:761–5.

    Article  Google Scholar 

  16. Mori N, Gotoh M, Chang SS, Igai H, Misaki N, Yamamoto Y, et al. Reconstruction of emphysematous lung tissue using slowly released basic fibroblast growth factor from gelatin microspheres. ASAIO J. 2008;54:622–6.

    Article  CAS  Google Scholar 

  17. Chang SS, Yokomise H, Matsuura N, Gotoh M, Tabata Y. Novel therapeutic approach for pulmonary emphysema using gelatin microspheres releasing basic fibroblast growth factor in a canine model. Surg Today. 2014;44:1536–41.

    Article  CAS  Google Scholar 

  18. Topol M, Maslon A. The problem of direct lymph drainage of the bronchopulmonary segments into the mediastinal and hilar lymph nodes. Clin Anat. 2009;22:509–16.

    Article  Google Scholar 

  19. Takeda AH, Watanabe Y, Nagata T, Aoki M, Umehara T, Suzuki S, et al. Detection of alternative subpleural lymph flow pathways using indocyanine green fluorescence. Surg Today. 2018;48:640–8.

    Article  Google Scholar 

  20. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  CAS  Google Scholar 

  21. Ueda K, Tanaka T, Jinbo M, Yagi T, Li TS, Hamano K. Sutureless pneumostasis using polyglycolic acid mesh as artificial pleura during video-assisted major pulmonary resection. Ann Thorac Surg. 2007;84:1858–61.

    Article  Google Scholar 

  22. Gotoh M, Okamoto T, Yamamoto Y, Liu D, Kameyama K, Hayashi E, et al. Development of a canine model of pulmonary emphysema and imaging of the emphysematous lung with infrared thoracoscopy. J Thorac Cardiovasc Surg. 2003;126:1916–21.

    Article  Google Scholar 

  23. Tabata Y, Ikada Y. Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with different biodegradabilities. Biomaterials. 1999;20:2169–75.

    Article  CAS  Google Scholar 

  24. Yamamoto M, Ikada Y, Tabata Y. Controlled release of growth factors based on biodegradation of gelatin hydrogel. J Biomater Sci Polym Ed. 2001;12:77–88.

    Article  CAS  Google Scholar 

  25. Gillooly M, Lamb D, Farrow AS. New automated technique for assessing emphysema on histological sections. J Clin Pathol. 1991;44:1007–11.

    Article  CAS  Google Scholar 

  26. Morino S, Nakamura T, Toba T, Takahashi M, Kushibiki T, Tabata Y, et al. Fibroblast growth factor-2 induces recovery of pulmonary blood flow in canine emphysema models. Chest. 2005;128:920–6.

    Article  CAS  Google Scholar 

  27. Morino S, Toba T, Tao H, Araki M, Shimizu Y, Nakamura T, et al. Fibroblast growth factor-2 promotes recovery of pulmonary function in a canine models of elastase-induced emphysema. Exp Lung Res. 2007;33:15–26.

    Article  Google Scholar 

  28. Edelman ER, Nugent MA, Karnovsky MJ. Perivascular and intravenous administration of basic fibroblast growth factor: vascular and solid organ deposition. Proc Natl Acad Sci USA. 1993;90:1513–7.

    Article  CAS  Google Scholar 

  29. Matsuura N, Go T, Fujiwara A, Nakano T, Nakashima N, Tarumi S, et al. Lymphatic invasion is a cause of local recurrence after wedge resection of primary lung cancer. Gen Thorac Cardiovasc Surg. 2019;67:861–6.

    Article  Google Scholar 

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Acknowledgements

We thank Dr. Reiji Haba for helpful discussions regarding microscopic lung section evaluation. This work was supported by the Japan Society for the Promotion of Science KAKENHI (Grants-in-Aid for Scientific Research) (grant number 19K09308).

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Authors and Affiliations

  1. Department of General Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Yasuhiro Otsuki, Tetsuhiko Go, Ayumu Kato, Naoya Yokota, Atsushi Fujiwara, Natsumi Matsuura, Sung Soo Chang, Noriyuki Misaki & Hiroyasu Yokomise

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  1. Yasuhiro Otsuki
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  2. Tetsuhiko Go
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  3. Ayumu Kato
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  5. Atsushi Fujiwara
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  6. Natsumi Matsuura
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  7. Sung Soo Chang
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  8. Noriyuki Misaki
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  9. Hiroyasu Yokomise
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Correspondence to Yasuhiro Otsuki.

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Otsuki, Y., Go, T., Kato, A. et al. Regeneration of emphysematous lungs using gelatin sheets that release basic fibroblast growth factor. Surg Today 52, 1229–1235 (2022). https://doi.org/10.1007/s00595-022-02465-z

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