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Tracheal cartilage growth promotion by intra-tracheal administration of basic FGF

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Abstract

Purpose

This study aimed to investigate whether intra-tracheal administration of basic fibroblast growth factor (b-FGF) promotes the growth of tracheal cartilage.

Methods

Trachea of 4-week old mice were intubated and 2.5 μg b-FGF administered (Group 4) for periods from 1 to 5 days. Cervical tracheal outer diameter and tracheal ring length were compared in Group 1 (no intervention), Group 2 (tracheal intubation), Group 3 (intra-tracheal administration of distilled water) and Group 4, at 8 weeks of age. Outer diameter and tracheal ring length in Group 4 were also compared with that in Group 1 at 12 and 16 weeks of age.

Results

At 8 weeks of age, tracheal ring length with b-FGF administration for more than 4 days in Group 4 was significantly increased over that following 1-day administration. At 8 weeks of age, mean outer diameter and the mean tracheal ring length in Group 4 were significantly greater than in the other groups. Mean outer diameter and mean tracheal ring length were significantly greater in Group 4 than in Group 1 at 12 and 16 weeks of age.

Conclusion

This study has shown that intra-tracheal administration of b-FGF enlarges the tracheal lumen.

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References

  1. Derfoul A, Perkins GL, Hall DJ, Tuan RS (2006) Glucocorticoids promote chondrogenic differentiation of adult human mesenchymal stem cells by enhancing expression of cartilage extracellular matrix genes. Stem Cells 24:1487–1495

    Article  CAS  Google Scholar 

  2. Yoo JU, Barthel TS, Nishimura K, Solchaga L, Caplan AI, Goldberg VM, Johnstone B (1998) The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells. J Bone Joint Surg Am 80:1745–1757

    Article  CAS  Google Scholar 

  3. Pogue R, Lyons K (2006) BMP signaling in the cartilage growth plate. Curr Top Dev Biol 76:1–48

    Article  CAS  Google Scholar 

  4. Solchaga LA, Penick K, Porter JD, Goldberg VM, Caplan AI, Welter JF (2005) FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J Cell Physiol 203:398–409

    Article  CAS  Google Scholar 

  5. An C, Cheng Y, Yuan Q, Li J (2010) IGF-1 and BMP-2 induces differentiation of adipose-derived mesenchymal stem cells into chondrocytes-like cells. Ann Biomed Eng 38:1647–1654. https://doi.org/10.1007/s10439-009-9892-x

    Article  PubMed  Google Scholar 

  6. Wakitani S, Imoto K, Kimura T, Ochi T, Matsumoto K, Nakamura T (1997) Hepatocyte growth factor facilitates cartilage repair. Full thickness articular cartilage defect studied in rabbit knees. Acta Orthop Scand 68:474–480

    Article  CAS  Google Scholar 

  7. Cook SD, Patron LP, Salkeld SL, Rueger DC (2003) Repair of articular cartilage defects with osteogenic protein-1 (BMP-7) in dogs. J Bone Joint Surg Am 85(A Suppl 3):116–123

    Article  Google Scholar 

  8. Sellers RS, Peluso D, Morris EA (1997) The effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the healing of full-thickness defects of articular cartilage. J Bone Joint Surg Am 79:1452–1463

    Article  CAS  Google Scholar 

  9. Otsuka Y, Mizuta H, Takagi K, Iyama K, Yoshitake Y, Nishikawa K, Suzuki F, Hiraki Y (1997) Requirement of fibroblast growth factor signaling for regeneration of epiphyseal morphology in rabbit full-thickness defects of articular cartilage. Dev Growth Differ 39:143–156

    Article  CAS  Google Scholar 

  10. Igai H, Chang SS, Gotoh M, Yamamoto Y, Misaki N, Okamoto T, Yamamoto M, Tabata Y, Yokomise H (2006) Regeneration of canine tracheal cartilage by slow release of basic fibroblast growth factor from gelatin sponge. ASAIO J 52:86–91

    Article  CAS  Google Scholar 

  11. Komura M, Komura H, Kanamori Y, Tanaka Y, Suzuki K, Sugiyama M, Nakahara S, Kawashima H, Hatanaka A, Hoshi K, Ikada Y, Tabata Y, Iwanaka T (2008) An animal model study for tissueengineered trachea fabricated from a biodegradable scaffold using chondrocytes to augment repair of tracheal stenosis. J Pediatr Surg 43:2141–2146. https://doi.org/10.1016/j.jpedsurg.2008.08.038

    Article  PubMed  Google Scholar 

  12. Masters IB, Chang AB (2009) Tracheobronchomalacia in children. Expert Rev Respir Med 3:425–439

    Article  Google Scholar 

  13. Komura M, Komura H, Tanaka Y, Kanamori Y, Sugiyama M, Nakahara S, Kawashima H, Suzuki K, Hoshi K, Iwanaka T (2008) Human tracheal chondrocytes as a cell source for augmenting stenotic tracheal segments: the first feasibility study in an in vivo culture system. Pediatr Surg Int 24:1117–1121. https://doi.org/10.1007/s00383-008-2218-5

    Article  PubMed  Google Scholar 

  14. Komura M, Komura H, Kanamori Y, Tanaka Y, Ohatani Y, Ishimaru T, Sugiyama M, Hoshi K, Iwanaka T (2010) Study of mechanical properties of engineered cartilage in an in vivo culture for design of a biodegradable scaffold. Int J Artif Organs 33:775–781

    Article  CAS  Google Scholar 

  15. Komura M, Komura H, Otani Y, Kanamori Y, Iwanaka T, Hoshi K, Tsuyoshi T, Tabata Y (2013) The junction between hyaline cartilage and engineered cartilage in rabbits. Laryngoscope 123:1547–1551. https://doi.org/10.1002/lary.23269

    Article  CAS  PubMed  Google Scholar 

  16. Ishimaru T, Komura M, Komura H, Otani Y, Komuro H, Sugiyma M, Terawaki K, Suzuki K, Tabata Y, Iwanaka T (2013) Slow release of basic fibroblast growth factor (b-FGF) promotes growth of tracheal cartilage. J Pediatr Surg 48:288–292. https://doi.org/10.1016/j.jpedsurg.2012.11.003

    Article  PubMed  Google Scholar 

  17. Komura M, Komura H, Konishi K, Ishimaru T, Hoshi K, Takato T, Tabata Y, Iwanaka T (2014) Promotion of tracheal cartilage growth by intra-tracheal injection of basic fibroblast growth factor (b-FGF). J Pediatr Surg 49:296–300. https://doi.org/10.1016/j.jpedsurg.2013.11.040

    Article  PubMed  Google Scholar 

  18. McNamara VM, Crabbe DC (2004) Tracheomalacia. Paediatr Respir Rev 5:147–154

    Article  CAS  Google Scholar 

  19. Benson RC (1978) KuesHA. Fluorescence properties of indocyanine green as related to angiography Phys Med boil 23:159–163

    CAS  Google Scholar 

  20. Rino Y, Yukawa N, Sato T, Yamamoto N, Tamagawa H, Hasegawa S, Oshima T, Yoshikawa T, Masuda M, Imada T (2014) Visualization of blood supply route to the reconstructed stomach by indocyanine green fluorescence imaging during esophagectomy. BMC Med Imaging 14:18. https://doi.org/10.1186/1471-2342-14-18

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ishimaru T, Komura M, Sugiyma M, Komura H, Arai M, Fujishiro J, Uotani C, Miyakawa K, Kakihara T, Hoshi K, Takato T, Tabata Y, Komuro H, Iwanaka T (2015) Slow release of basic fibroblast growth factor (b-FGF) enhances mechanical properties of rat trachea. J Pediatr Surg 50:255–259. https://doi.org/10.1016/j.jpedsurg.2014.11.012

    Article  PubMed  Google Scholar 

  22. Igai H, Chang SS, Gotoh M, Yamamoto Y, Yamamoto M, Tabata Y, Yokomise H (2009) Widespread and early tracheal cartilage regeneration by synchronous slow release of b-FGF and BMP-2. ASAIO J 55:266–270. https://doi.org/10.1097/MAT.0b013e318197f7e3

    Article  CAS  PubMed  Google Scholar 

  23. Ellman MB, An HS, Muddasani P, Im HJ (2008) Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis. Gene 420:82–89. https://doi.org/10.1016/j.gene.2008.04.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lazarous DF, Shou M, Stiber JA, Dadhania DM, Thirumurti V, Hodge E, Unger EF (1997) Pharmacodynamics of basic fibroblast growth factor: route of administration determines myocardial and systemic distribution. Cardiovasc Res 36:78–85

    Article  CAS  Google Scholar 

  25. Edelman ER, Nugent MA, Karnovsky MJ (1993) Perivascular and intravenous administration of basic fibroblast growth factor: vascular and solid organ deposition. Proc Natl Acad Sci USA 90:1513–1517

    Article  CAS  Google Scholar 

  26. Isogai N, Morotomi T, Hayakawa S, Munakata H, Tabata Y, Ikada Y, Kamiishi H (2005) Combined chondrocyte-copolymer implantation with slow release of basic fibroblast growth factor for tissue engineering an auricular cartilage construct. J Biomed Mater Res A 74:408–418

    Article  Google Scholar 

  27. Igai H, Yamamoto Y, Chang SS, Yamamoto M, Tabata Y, Yokomise H (2007) Tracheal cartilage regeneration by slow release of basic fibroblast growth factor from a gelatin sponge. J Thorac Cardiovasc Surg 134:170–175

    Article  Google Scholar 

  28. Yoo JJ, Park HJ, Lee I, Atala A (1999) Autologous engineered cartilage rods for penile reconstruction. J Urol 162:1119–1121

    Article  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from Kawano Masanori Memorial Foundation for Promotion of Pediatrics 2009 and the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 22591977). We appreciate the technical support provided by Nobuyuki Kikuchi, who is a technician in the Department of Tissue Engineering in the Graduate School of Medicine, University of Tokyo The authors give special thanks to Kaken Pharmaceutical Co. Ltd. for providing human recombinant fibroblast growth factor-2 (b-FGF) for cell culture.

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Authors and Affiliations

Authors

Contributions

MK, HK, TI and KK performed the experiments. MK, HK, HK and TI designed the research study. KH and TT contributed essential tools. MK, HK, KH, TT and TI analysed the data, and MK and HK wrote the paper.

Corresponding author

Correspondence to Makoto Komura.

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Conflict of interest

Makoto Komura received a contributed human recombinant fibroblast growth factor-2 (b-FGF) for cell culture from Kaken Pharmaceutical Co. Ltd.

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Komura, M., Komura, H., Ishimaru, T. et al. Tracheal cartilage growth promotion by intra-tracheal administration of basic FGF. Pediatr Surg Int 36, 33–41 (2020). https://doi.org/10.1007/s00383-019-04576-0

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