Skip to content
2000
Volume 20, Issue 6
  • ISSN: 1574-888X
  • E-ISSN: 2212-3946

Abstract

Background

The use of decellularized tissues as cell culture scaffolds is an exciting new direction in regenerative medicine because they may provide the instructional context for cell development and function.

Objective

Building a scaffold with biomimetic chemical, structural, and functional features is crucial for lung tissue healing. Due to the diverse nature of their structure, a decellularized lung matrix derived from both allogeneic and xenogeneic sources is regarded as an ideal scaffold for lung regeneration.

Methods

By decellularizing rat lungs using a combination of chemical and physical methods, we were able to build a scaffold for lung tissue engineering. A decellularized lung was tested for DNA content, and histologically, it was shown to be totally free of cells after using this process.

Results

The decellularized lung was biocompatible for the growth of human endometrial stem cells (hEnSCs), as evidenced by scanning electron microscopy (SEM), an MTS assay, and Hematoxylin and Eosin (H&E) staining. In addition, we found that decellularized scaffolds induced lung epithelial cell differentiation from EnSCs by upregulating a subset of genes. Lung epithelial cell development from stem cells was also induced by decellularized scaffolds, as shown by an increase in the expression of a gene that is only expressed in lung epithelial cells. The strong level of acellularized scaffold affinity for cell adhesion, proliferation, and growth was also shown to promote lung lesion regeneration in rats after four weeks of treatment, according to research.

Conclusion

In summary, the decellularized lung scaffold that has been developed offers a highly accurate framework for the effective restoration of lung tissues. These scaffolds prove to be valuable tools for investigating the mechanisms by which the tissue microenvironment facilitates the growth, differentiation, and function of lung epithelial-like cells, ultimately contributing to the beneficial outcomes of lung repair.

Loading

Article metrics loading...

/content/journals/cscr/10.2174/011574888X285428240521130119
2025-07-01
2026-02-05
Loading full text...

Full text loading...

References

  1. IlzeB. Avoidable mortality: OECD/Eurostat lists of preventable and treatable causes of death.2022Available from: https://www.oecd.org/health/health-systems/Avoidable-mortality-2019-Joint-OECD-Eurostat-List-preventable-treatable-causes-of-death.pdf
  2. AllinsonJ.P. ChaturvediN. WongA. ShahI. DonaldsonG.C. WedzichaJ.A. HardyR. Early childhood lower respiratory tract infection and premature adult death from respiratory disease in Great Britain: A national birth cohort study.Lancet2023401103831183119310.1016/S0140‑6736(23)00131‑936898396
    [Google Scholar]
  3. StablerC.T. LechtS. MondrinosM.J. GoulartE. LazaroviciP. LelkesP.I. Revascularization of decellularized lung scaffolds: Principles and progress.Am. J. Physiol. Lung Cell. Mol. Physiol.201530911L1273L128510.1152/ajplung.00237.201526408553
    [Google Scholar]
  4. AshmawyR ZakiA Efficacy and safety of inhaled heparin in asthmatic and chronic obstructive pulmonary disease patients: A systematic review and a meta-analysisSci Rep. 20231311332610.1038/s41598‑023‑40489‑8
    [Google Scholar]
  5. TebyanianH. KaramiA. MotavallianE. AslaniJ. SamadikuchaksaraeiA. ArjmandB. NouraniM.R. A comparative study of rat lung decellularization by chemical detergents for lung tissue engineering.Open Access Maced. J. Med. Sci.20175785986510.3889/oamjms.2017.17929362610
    [Google Scholar]
  6. MulliganM.S. ShearonT.H. WeillD. PaganiF.D. MooreJ. MurrayS. Heart and lung transplantation in the United States, 1997-2006.Am. J. Transplant.20088497798710.1111/j.1600‑6143.2008.02175.x18336700
    [Google Scholar]
  7. PrakashYS TschumperlinDJ StenmarkKR Coming to terms with tissue engineering and regenerative medicine in the lung.Am. J. Physiol. Lung Cell. Mol. Physiol.2015309L62 384510.1152/ajplung.00204.2015
    [Google Scholar]
  8. NicholsJ.E. NilesJ.A. CortiellaJ. Design and development of tissue engineered lung.Organogenesis200952576110.4161/org.5.2.856419794900
    [Google Scholar]
  9. ReichenspurnerH. Overview of tacrolimus-based immunosuppression after heart or lung transplantation.J Heart Lung Transplant200524119130
    [Google Scholar]
  10. OttH.C. MatthiesenT.S. GohS.K. BlackL.D. KrenS.M. NetoffT.I. TaylorD.A. Perfusion-decellularized matrix: Using nature’s platform to engineer a bioartificial heart.Nat. Med.200814221322110.1038/nm168418193059
    [Google Scholar]
  11. HasanzadehE. AmoabedinyG. HaghighipourN. GholamiN. MohammadnejadJ. ShojaeiS. Salehi-NikN. The stability evaluation of mesenchymal stem cells differentiation toward endothelial cells by chemical and mechanical stimulation. In vitro. Cell. Dev. Biol. Anim.201753981882610.1007/s11626‑017‑0165‑y28702926
    [Google Scholar]
  12. AbpeikarZ MoradiL JavdaniM Characterization of macroporous polycaprolactone/silk fibroin/gelatin/ascorbic acid composite scaffolds and in vivo results in a rabbit model for meniscus cartilage repair.Cartilage2021132_suppl1583S1601S
    [Google Scholar]
  13. SchmidtD. MolA. OdermattB. NeuenschwanderS. BreymannC. GössiM. GenoniM. ZundG. HoerstrupS.P. Engineering of biologically active living heart valve leaflets using human umbilical cord-derived progenitor cells.Tissue Eng.200612113223323210.1089/ten.2006.12.322317518636
    [Google Scholar]
  14. NiklasonL.E. GaoJ. AbbottW.M. HirschiK.K. HouserS. MariniR. LangerR. Functional arteries grown in vitro.Science1999284541348949310.1126/science.284.5413.48910205057
    [Google Scholar]
  15. AtalaA. BauerS.B. SokerS. YooJ.J. RetikA.B. Tissue-engineered autologous bladders for patients needing cystoplasty.Lancet200636795181241124610.1016/S0140‑6736(06)68438‑916631879
    [Google Scholar]
  16. AndradeC.F. WongA.P. WaddellT.K. KeshavjeeS. LiuM. Cell-based tissue engineering for lung regeneration.Am. J. Physiol. Lung Cell. Mol. Physiol.20072922L510L51810.1152/ajplung.00175.200617028264
    [Google Scholar]
  17. DingT. LuoZ.J. ZhengY. HuX.Y. YeZ.X. Rapid repair and regeneration of damaged rabbit sciatic nerves by tissue-engineered scaffold made from nano-silver and collagen type I.Injury201041552252710.1016/j.injury.2009.04.00319524233
    [Google Scholar]
  18. MobarakehZ.T. AiJ. YazdaniF. SorkhabadiS.M.R. GhanbariZ. JavidanA.N. Mortazavi-TabatabaeiS.A. MassumiM. BaroughS.E. Human endometrial stem cells as a new source for programming to neural cells.Cell Biol. Int. Rep.201219171410.1042/CBR2011000923124318
    [Google Scholar]
  19. OrazizadehM. RashidiI. SaremiJ. LatifiM. Focal adhesion kinase (FAK) involvement in human endometrial remodeling during the menstrual cycle.Iran. Biomed. J.20091329510119471549
    [Google Scholar]
  20. LiuM. ZengX. MaC. YiH. AliZ. MouX. LiS. DengY. HeN. Injectable hydrogels for cartilage and bone tissue engineering.Bone Res.2017511701410.1038/boneres.2017.1428584674
    [Google Scholar]
  21. ElderB.D. EleswarapuS.V. AthanasiouK.A. Extraction techniques for the decellularization of tissue engineered articular cartilage constructs.Biomaterials200930223749375610.1016/j.biomaterials.2009.03.05019395023
    [Google Scholar]
  22. BordbarS. Lotfi BakhshaieshN. KhanmohammadiM. SayahpourF.A. AliniM. Baghaban EslaminejadM. Production and evaluation of decellularized extracellular matrix hydrogel for cartilage regeneration derived from knee cartilage.J. Biomed. Mater. Res. A2020108493894610.1002/jbm.a.3687131894891
    [Google Scholar]
  23. BadylakS.F. TaylorD. UygunK. Whole-organ tissue engineering: Decellularization and recellularization of three-dimensional matrix scaffolds.Annu. Rev. Biomed. Eng.2011131275310.1146/annurev‑bioeng‑071910‑12474321417722
    [Google Scholar]
  24. VertreesR.A. ZwischenbergerJ.B. BoorP.J. PopovV. McCarthyM. GoodwinT. SolleyT. Cellular differentiation in three-dimensional lung cell cultures.Cancer Biol. Ther.20087340441110.4161/cbt.7.3.536818075303
    [Google Scholar]
  25. HasanzadehE. MahmoodiN. BasiriA. Esmaeili RanjbarF. HassannejadZ. Ebrahimi-BaroughS. AzamiM. AiJ. Rahimi-MovagharV. Proanthocyanidin as a crosslinking agent for fibrin, collagen hydrogels and their composites with decellularized Wharton’s-jelly-extract for tissue engineering applications.J. Bioact. Compat. Polym.202035655457110.1177/0883911520956252
    [Google Scholar]
  26. KuşoğluA. YangınK. ÖzkanS.N. Different decellularization methods in bovine lung tissue reveals distinct biochemical composition, stiffness, and viscoelasticity in reconstituted hydrogels.ACS Appl Bio Mater.20236793805
    [Google Scholar]
  27. PetersenT.H. CalleE.A. ZhaoL. LeeE.J. GuiL. RaredonM.B. GavrilovK. YiT. ZhuangZ.W. BreuerC. HerzogE. NiklasonL.E. Tissue-engineered lungs for in vivo implantation.Science2010329599153854110.1126/science.118934520576850
    [Google Scholar]
  28. OttH.C. ClippingerB. ConradC. SchuetzC. PomerantsevaI. IkonomouL. KottonD. VacantiJ.P. Regeneration and orthotopic transplantation of a bioartificial lung.Nat. Med.201016892793310.1038/nm.219320628374
    [Google Scholar]
  29. PetersenT.H. CalleE.A. ColehourM.B. NiklasonL.E. Matrix composition and mechanics of decellularized lung scaffolds.Cells Tissues Organs2012195322223110.1159/00032489621502745
    [Google Scholar]
  30. LiaoJ. JoyceE.M. SacksM.S. Effects of decellularization on the mechanical and structural properties of the porcine aortic valve leaflet.Biomaterials20082981065107410.1016/j.biomaterials.2007.11.00718096223
    [Google Scholar]
  31. CaoR. ZhanA. CiZ. WangC. SheY. XuY. XiaoK. XiaH. ShenL. MengD. ChenC. A biomimetic biphasic scaffold consisting of decellularized cartilage and decalcified bone matrixes for osteochondral defect repair.Front. Cell Dev. Biol.2021963900610.3389/fcell.2021.63900633681223
    [Google Scholar]
  32. TanH. YangB. DuanX. WangF. ZhangY. JinX. DaiG. YangL. The promotion of the vascularization of decalcified bone matrix in vivo by rabbit bone marrow mononuclear cell-derived endothelial cells.Biomaterials200930213560356610.1016/j.biomaterials.2009.03.02919359037
    [Google Scholar]
  33. NooriA Mokhber DezfouliMR RajabiS Decellularized lung extracellular matrix scaffold promotes human embryonic stem cell differentiation towards alveolar progenitorsCell J.202325372382
    [Google Scholar]
  34. LeeJ.S. ChoiY.S. ChoS.W. Decellularized tissue matrix for stem cell and tissue engineering.Adv. Exp. Med. Biol.2018106416118010.1007/978‑981‑13‑0445‑3_1030471032
    [Google Scholar]
  35. HuangS.X.L. IslamM.N. O’NeillJ. HuZ. YangY.G. ChenY.W. MumauM. GreenM.D. Vunjak-NovakovicG. BhattacharyaJ. SnoeckH.W. Efficient generation of lung and airway epithelial cells from human pluripotent stem cells.Nat. Biotechnol.2014321849110.1038/nbt.275424291815
    [Google Scholar]
  36. XueJX GongYY ZhouGD LiuW CaoY ZhangWJ Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells induced by acellular cartilage sheets.Biomaterials201233583284010.1016/j.biomaterials.2012.04.054
    [Google Scholar]
  37. RannelsD.E. RannelsS.R. Influence of the extracellular matrix on type 2 cell differentiation.Chest198996116517310.1378/chest.96.1.1652661156
    [Google Scholar]
  38. YuanH IngenitoEP SukiB Dynamic properties of lung parenchyma: Mechanical contributions of fiber network and interstitial cells.J. Appl. Physiol.19978314201431
    [Google Scholar]
  39. CortiellaJ. NilesJ. CantuA. BrettlerA. PhamA. VargasG. WinstonS. WangJ. WallsS. NicholsJ.E. Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation.Tissue Eng. Part A20101682565258010.1089/ten.tea.2009.073020408765
    [Google Scholar]
  40. EnglerA.J. SenS. SweeneyH.L. DischerD.E. Matrix elasticity directs stem cell lineage specification.Cell2006126467768910.1016/j.cell.2006.06.04416923388
    [Google Scholar]
  41. EnglerA.J. SweeneyH.L. DischerD.E. SchwarzbauerJ.E. Extracellular matrix elasticity directs stem cell differentiation.J. Musculoskelet. Neuronal Interact.20077433518094500
    [Google Scholar]
  42. ShannonJ.M. MasonR.J. JenningsS.D. Functional differentiation of alveolar type II epithelial cells in vitro: Effects of cell shape, cell-matrix interactions and cell-cell interactions.Biochim. Biophys. Acta Mol. Cell Res.1987931214315610.1016/0167‑4889(87)90200‑X3663713
    [Google Scholar]
  43. MondrinosM.J. KoutzakiS. JiwanmallE. LiM. DechadarevianJ.P. LelkesP.I. FinckC.M. Engineering three-dimensional pulmonary tissue constructs.Tissue Eng.200612471772810.1089/ten.2006.12.71716674286
    [Google Scholar]
  44. ChenP. MarsilioE. GoldsteinR.H. YannasI.V. SpectorM. Formation of lung alveolar-like structures in collagen-glycosaminoglycan scaffolds in vitro.Tissue Eng.2005119-101436144810.1089/ten.2005.11.143616259599
    [Google Scholar]
  45. SugiharaH. TodaS. MiyabaraS. FujiyamaC. YonemitsuN. Reconstruction of alveolus-like structure from alveolar type II epithelial cells in three-dimensional collagen gel matrix culture.Am. J. Pathol.199314237837928456939
    [Google Scholar]
  46. RabataA. FedrR. SoucekK. HamplA. KoledovaZ. 3D cell culture models demonstrate a role for fgf and wnt signaling in regulation of lung epithelial cell fate and morphogenesis.Front. Cell Dev. Biol.2020857410.3389/fcell.2020.0057432850782
    [Google Scholar]
  47. TiwariS.K. WangS. SmithD. CarlinA.F. RanaT.M. Revealing tissue-specific SARS-CoV-2 infection and host responses using human stem cell-derived lung and cerebral organoids.Stem Cell Reports202116343744510.1016/j.stemcr.2021.02.00533631122
    [Google Scholar]
  48. da RosaNN AppelJM IriodaAC MogharbelBF Three-dimensional bioprinting of an in vitro lung model.Int J Mol Sci.2023246585210.3390/ijms24065852
    [Google Scholar]
  49. WangZ. LaiJ. LiY. ZhouH. AlhaskawiA. LiP. ShenX. LuH. TuT. Could E-cadherin overexpression promote epithelial differentiation of human adipose-derived stem cells by mediating mesenchymal-to-epithelial transition?Med. Hypotheses202317111101610.1016/j.mehy.2023.111016
    [Google Scholar]
  50. LinL.P. TanM.T.T. Biosensors for the detection of lung cancer biomarkers: A review on biomarkers, transducing techniques and recent graphene-based implementations.Biosens. Bioelectron.202323711549210.1016/j.bios.2023.11549237421797
    [Google Scholar]
  51. FicialM. AntonagliaC. ChilosiM. SantagiulianaM. TahseenA.O. ConfalonieriD. ZandonàL. BussaniR. ConfalonieriM. Keratin-14 expression in pneumocytes as a marker of lung regeneration/repair during diffuse alveolar damage.Am. J. Respir. Crit. Care Med.201418991142114510.1164/rccm.201312‑2134LE24787069
    [Google Scholar]
  52. MendezJ.J. GhaediM. SteinbacherD. NiklasonL.E. Epithelial cell differentiation of human mesenchymal stromal cells in decellularized lung scaffolds.Tissue Eng. Part A20142011-121735174610.1089/ten.tea.2013.064724393055
    [Google Scholar]
  53. KawaiN. OujiY. SakagamiM. TojoT. SawabataN. YoshikawaM. TaniguchiS. Induction of lung-like cells from mouse embryonic stem cells by decellularized lung matrix.Biochem. Biophys. Rep.201815333810.1016/j.bbrep.2018.06.00529942870
    [Google Scholar]
  54. BahramiN. bordbarS. HasanzadehE. GoodarziA. AiA. MohamadniaA. The effect of decellularized cartilage matrix scaffolds combined with endometrial stem cell–derived osteocytes on osteochondral tissue engineering in rats. In vitro. Cell. Dev. Biol. Anim.202258648049010.1007/s11626‑022‑00692‑935727496
    [Google Scholar]
  55. BianL. GuvendirenM. MauckR.L. BurdickJ.A. Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis.Proc. Natl. Acad. Sci. USA201311025101171012210.1073/pnas.121410011023733927
    [Google Scholar]
  56. TemenoffJ.S. MikosA.G. Review: Tissue engineering for regeneration of articular cartilage.Biomaterials200021543144010.1016/S0142‑9612(99)00213‑610674807
    [Google Scholar]
  57. WangZ. LiZ. LiZ. WuB. LiuY. WuW. Cartilaginous extracellular matrix derived from decellularized chondrocyte sheets for the reconstruction of osteochondral defects in rabbits.Acta Biomater.20188112914510.1016/j.actbio.2018.10.00530300711
    [Google Scholar]
/content/journals/cscr/10.2174/011574888X285428240521130119
Loading
/content/journals/cscr/10.2174/011574888X285428240521130119
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test