Prospects of the tissue engineering lung development with the methods of regenerative medicine (review)

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


Deficit of donor organs, the need for lifelong immunosuppressive therapy, even in the case of successful lung transplantation, high risk of death in the postoperative period are forced to look for the new ways to treat terminally ill patients, requiring organ transplants. In the last decade, much attention is given to methods of regenerative medicine to repair or replace the function of damaged tissues and organs. Creating functional lungs in the laboratory will hopefully solve the problem of donor organs shortage. The study of morphological properties of biological scaffolds, deeper understanding of stem cells and progenitor cells behavior led to the idea of using decellularization methods followed by recellularization with autologous cells for tissue engineered trachea, lungs, heart and kidney creation Recellularized solid organs can perform organ-specific function in vitro conditions, indicating the potential clinical use of these methods This review presents the current data about lung decellularization and recellularization methods to increase efficiency and improve the quality of the biological scaffold and discusses the main aspects of lung transplantation in animal models and perspectives of lung bioengineering

Full Text

Restricted Access

About the authors

E. V Kuevda

Kuban State Medical University

E. A Gubareva

Kuban State Medical University


A. S Sotnichenko

Kuban State Medical University

I. V Gilevich

Kuban State Medical University

I. S Gumenyuk

Kuban State Medical University

P. Macchiarini

Kuban State Medical University; Karolinska Institutet


  1. Lim M. L., Jungebluth P., Macchiarini P. The Implications of stem cell applications for diseases of the respiratory system Adv Biochem Eng. Biotechnol. 2013; 130:39-54.
  2. Calle E.A. , Petersen T. H., Niklason L. E. Procedure for lung engineering. J. Vis. Exp. 2011; 49: 26-51.
  3. Wang D., Morales J. E., Calame D. G. et al. Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice. Mol. Ther. 2012; 18(3):625-34.
  4. Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663-76.
  5. Hoshiba T. , Lu H. , Kawazoe N. et al. Decellularized matrices for tissue engineering. Expert Opin. Biol. Ther. 2010; 10(12): 1717-28.
  6. Kotsimbos T., Williams T.J., Anderson G. P. Update on lung transplantation: programmes, patients and prospects Eur Respir Rev. 2012; 21: 271-305.
  7. Zafar S. Y. , Howell D. N. , Gockerman J. P. Malignancy after solid organ transplantation: an overview. Oncologist 2008; 13:769-78.
  8. Valapour M. , Paulson K., Smith J. M. et al. Annual Data Report: lung. Am. J. Transplant. 2013; 13(Suppl 1):149-77.
  9. Oto T. , Okada Y. , Bando T. et al. Japanese society of lung and heart-lung transplantation. Registry of the Japanese society of lung and heart-lung transplantation: the official Japanese lung transplantation report 2012. Gen. Thorac. Cardiovasc. Surg. 2013; 61:208-11.
  10. Tsuchiya T., Sivarapatna A., Rocco K. et al. Future prospects for tissue engineered lung transplantation. Decellularization and recellularization-based whole lung regeneration. Organogenesis 2014; 10(2): 196-207.
  11. Petersen T. H., Calle E.A., Zhao L. et al. Tissue-engineered lungs for in vivo implantation. Science 2010; 329: 538-41.
  12. Ott H. C., Clippinger B., Conrad C. et al. Regeneration and orthotopic transplantation of a bioartificial lung. Nat. Med. 2010; 16: 927-33
  13. Price A. P., England K.A., Matson A. M. et al. Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded. Tissue Eng. Part A 2010; 16: 2581-91.
  14. Song J. J. , Kim S. S., Liu Z. et al. Enhanced in vivo function of bioartificial lungs in rats. Ann. Thorac. Surg. 2011; 92: 998-1005.
  15. Cortiella J., Niles J., Cantu A. et al. Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation. Tissue Eng. Part A 2010; 16:2565-80.
  16. Daly A. B., Wallis J. M., Borg Z. D. et al. Initial binding and recellularization of decellularized mouse lung scaffolds with bone marrow-derived mesenchymal stromal cells. Tissue Eng. Part A 2012; 18:1-16.
  17. Wallis J. M. , Borg Z. D., Daly A. B. et al. Comparative assessment of detergent-based protocols for mouse lung decellularization and recellularization. Tissue Eng. Part C Methods 2012; 18: 420-32.
  18. Jensen T., Roszell B., Zang F. et al. A rapid lung decellularization protocol supports embryonic stem cell differentiation in vitro and following implantation. Tissue Eng. Part C Methods 2012; 18: 632-46
  19. Bonvillain R. W., Danchuk S., Sullivan D. E. et al. A nonhuman primate model of lung regeneration: detergent-mediated decellularization and initial in vitro recellularization with mesenchymal stem cells. Tissue Eng. Part A 2012; 18: 2437-52.
  20. Gilbert T.W., Sellaro T. L., Badylak S. F. Decellularization of tissues and organs. Biomaterials 2006; 27: 3675-83.
  21. McDevitt C.A., Wildey G. M., Cutrone R. M. Transforming growth factor-beta1 in a sterilized tissue derived from the pig small intestine submucosa. J. Biomed. Mater. Res. A 2003; 67: 637-40.
  22. Crapo P. M., Gilbert T.W. , Badylak S. F. An overview of tissue and whole organ decellularization processes. Biomaterials 2011; 32: 3233-43
  23. Petersen T. H., Calle E.A., Colehour M. B. et al. Matrix composition and mechanics of decellularized lung scaffolds. Cells Tissues Organs 2012; 195: 222-31.
  24. Wallis J. M., Borg Z. D., Daly A. B. et al. Comparative assessment of detergent-based protocols for mouse lung decellularization and recellularization. Tissue Eng. Part C Methods 2012; 18: 420-32.
  25. Nagata S., Hanayama R., Kawane K. Autoimmunity and the clearance of dead cells. Cell 2010; 140(5): 619-30.
  26. Franzdóttir S. R., Axelsson I.T., Arason A.J. et al. Airway branching morphogenesis in three dimensional culture. Respir. Res. 2010; 11: 162-72.
  27. Huh D., Matthews B. D., Mammoto A. et al. Reconstituting organ-level lung functions on a chip. Science 2010; 328:1662-8.
  28. Gehr P., Bachofen M., Weibel E. R. The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir. Physiol. 1978; 32: 121-40.
  29. Maghsoudlou P., Georgiades F., Tyraskis A. et al. Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment. Biomaterials 2013; 34: 6638-48.
  30. Kuevda E., Gubareva E., Sotnichenko A. et al. Best decellularization protocol for tissue-engineered lungs. Proceedings of the World Conference on Regenerative Medicine; 2013 Oct 23-25; Leipzig; Germany. Regenerative Medicine 2013; 8 (Suppl 6): s21.
  31. Sayk F., Bos I. , Schubert U. et al. Histopathologic findings in a novel decellularized pulmonary homograft: an autopsy study. Ann. Thorac Surg 2005; 79: 1755-8
  32. Takagi K., Fukunaga S., Nishi A. et al. In vivo recellularization of plain decellularized xenografts with specific cell characterization in the systemic circulation: histological and immunohistochemical study. Artif. Organs 2006; 30: 233-41.
  33. Friedrich L. H., Jungebluth P. , Sjöqvist S. et al. Preservation of aortic root architecture and properties using a detergent-enzymatic perfusion protocol. Biomaterials 2014; 35(6): 1907-13.
  34. Baiguera S., Jungebluth P., Burns A., et al. Tissue engineered human tracheas for in vivo implantation. Biomaterials 2010; 31: 8931-38.
  35. Macchiarini P., Jungebluth P., Go T. et al. Clinical transplantation of a tissue-engineered airway. Lancet 2008; 372: 2023-30.
  36. Atala A., Bauer S. B. , Soker S. et al. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 2006; 367: 1241-6.
  37. Biancosino C., Zardo P. , Walles T. et al. Generation of a bioartificial fibromuscular tissue with autoregenerative capacities for surgical reconstruction. Cytotherapy 2006; 8: 178-83.
  38. Cebotari S. , Lichtenberg A., Tudorache I. et al. Clinical application of tissue engineered human heart valves using autologous progenitor cells. Circulation 2006; 114(Suppl I): 132-7.
  39. Hermanns M. I. , Unger R. E. , Kehe K. et al. Lung epithelial cell lines in coculture with human pulmonary microvascular endothelial cells: development of an alveolo-capillary barrier in vitro. Lab. Invest. 2004; 84: 736-52.
  40. Lwebuga-Mukasa J. , Inggar D., Madri J. Repopulation of a human alveolar matrix by adult rat type II pneumocytes in vitro. A novel system for type II pneumocyte culture. Exp. Cell Res. 1986; 162: 423-35
  41. Cortiella J., Niles J., Cantu A. et al. Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation. Tissue Eng. Part A 2010; 16: 2565-80.
  42. Ingenito E. P., Tsai L., Murthy S. et al. Autologous lung derived mesenchymal stem cell transplantation in experimental emphysema. Cell Transplant. 2012; 21(1): 175-89.
  43. Collas P., Hakelien A. M. Teaching cells new tricks. Trends Biotechnol. 2003; 21 (8): 354-361.
  44. Ambrosi D.J., Rasmussen T. P. Reprogramming mediated by stem cell fusion. J. Cell Mol. Med. 2005; 9(2): 320-330.
  45. Takahashi K. , Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4): 663-76.
  46. Petersen T. H. , Calle E.A. , Colehour M. B. et al. Bioreactor for the long-term culture of lung tissue. Cell Transplant. 2011; 20: 1117-26.
  47. Longmire T. A., Ikonomou L., Hawkins F. et al. Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells. Cell Stem Cell 2012; 10: 398-411.
  48. Shamis Y. , Hasson E., Soroker A. et al. Organ-specific scaffolds for in vitro expansion, differentiation, and organization of primary lung cells. Tissue Eng. Part C Methods 2011; 17: 861-70.
  49. Inanlou M. R., Baguma-Nibasheka M., Kablar B. The role of fetal breathing-like movements in lung organogenesis. Histol. Histopathol. 2005; 20: 1261-6.
  50. Petersen T. H., Calle E.A. , Colehour M. B. et al. Matrix composition and mechanics of decellularized lung scaffolds. Cells Tissues Organs 2012; 195: 222-31.
  51. Badylak S. F. Xenogeneic extracellular matrix as a scaffold for tissue reconstruction. Transpl. Immunol. 2004; 12: 367-77.
  52. Sokocevic D., Bonenfant N. R. , Wagner D. E. et al. The effect of age and emphysematous and fibrotic injury on the recellularization of decellularized lungs. Biomaterials 2013; 34: 3256-69.
  53. Daly K. A. , Stewart-Akers A. M. , Hara H. et al. Effect of the alphaGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model. Tissue Eng. Part A 2009; 15: 3877-88.
  54. McPherson T.B., Liang H. , Record R.D. et al. Galalpha(1,3) Gal epitope in porcine small intestinal submucosa. Tissue Eng. 2000; 6: 233-9
  55. Badylak S., Kokini K., Tullius B. et al. Morphologic study of small intestinal submucosa as a body wall repair device. J. Surg. Res. 2002; 103: 190-202.
  56. Nuininga J.E. , van Moerkerk H., Hanssen A. et al. Rabbit urethra replacement with a defined biomatrix or small intestinal submucosa Eur Urol 2003; 44: 266-71
  57. Cantu E., Parker W., Platt J.L. et al. Pulmonary xenotransplantation: rapidly progressing into the unknown. Am. J. Transplant. 2004; 4(Suppl 6): 25-35.
  58. Toledo-Pereyra L.H., Lopez-Neblina F. Xenotransplantation: a view to the past and an unrealized promise to the future. Exp. Clin. Transplant 2003; 1: 1-7.
  59. Ekser B., Rigotti P., Gridelli B. et al. Xenotransplantation of solid organs in the pig-to-primate model. Transpl. Immunol. 2009; 21: 87-92
  60. Nakakuki S. Bronchial tree, lobular division and blood vessels of the pig lung. J. Vet. Med. Sci. 1994; 56: 685-9.
  61. Daggett C.W. , Yeatman M., Lodge A. J. et al. Total respiratory support from swine lungs in primate recipients. J. Thorac. Cardiovasc. Surg. 1998; 115: 19-27.

Copyright (c) 2015 Eco-Vector

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 85657 от 21.07.2023 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies