Engineering Tissue-Informed Biomaterials to Advance Pulmonary Regenerative Medicine

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2021 Apr 26

PMID 33898484

Authors

Donald R Campbell Jr

Christiana N Senger

Amy L Ryan

Chelsea M Magin

Affiliations

Soon will be listed here.

Abstract

Biomaterials intentionally designed to support the expansion, differentiation, and three-dimensional (3D) culture of induced-pluripotent stem cells (iPSCs) may pave the way to cell-based therapies for chronic respiratory diseases. These conditions are endured by millions of people worldwide and represent a significant cause of morbidity and mortality. Currently, there are no effective treatments for the majority of advanced lung diseases and lung transplantation remains the only hope for many chronically ill patients. Key opinion leaders speculate that the novel coronavirus, COVID-19, may lead to long-term lung damage, further exacerbating the need for regenerative therapies. New strategies for regenerative cell-based therapies harness the differentiation capability of human iPSCs for studying pulmonary disease pathogenesis and treatment. Excitingly, biomaterials are a cell culture platform that can be precisely designed to direct stem cell differentiation. Here, we present a closer look at the state-of-the-art of iPSC differentiation for pulmonary engineering, offer evidence supporting the power of biomaterials to improve stem cell differentiation, and discuss our perspective on the potential for tissue-informed biomaterials to transform pulmonary regenerative medicine.

Citing Articles

Biomaterial-based 3D human lung models replicate pathological characteristics of early pulmonary fibrosis.

Tanneberger A, Blomberg R, Kary A, Lu A, Riches D, Magin C bioRxiv. 2025; .

PMID: 40027659 PMC: 11870410. DOI: 10.1101/2025.02.12.637970.

References

Metzger R, Klein O, Martin G, Krasnow M . The branching programme of mouse lung development. Nature. 2008; 453(7196):745-50. PMC: 2892995. DOI: 10.1038/nature07005. View

Liu F, Mallarino Haeger C, Dieffenbach P, Sicard D, Chrobak I, Coronata A . Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension. JCI Insight. 2016; 1(8). PMC: 4918638. DOI: 10.1172/jci.insight.86987. View

Spagnolo P, Balestro E, Aliberti S, Cocconcelli E, Biondini D, Casa G . Pulmonary fibrosis secondary to COVID-19: a call to arms?. Lancet Respir Med. 2020; 8(8):750-752. PMC: 7228737. DOI: 10.1016/S2213-2600(20)30222-8. View

Burdick J, Murphy W . Moving from static to dynamic complexity in hydrogel design. Nat Commun. 2012; 3:1269. DOI: 10.1038/ncomms2271. View

Sargeant T, Desai A, Banerjee S, Agawu A, Stopek J . An in situ forming collagen-PEG hydrogel for tissue regeneration. Acta Biomater. 2011; 8(1):124-32. DOI: 10.1016/j.actbio.2011.07.028. View

Burgstaller G, Oehrle B, Gerckens M, White E, Schiller H, Eickelberg O . The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease. Eur Respir J. 2017; 50(1). DOI: 10.1183/13993003.01805-2016. View

Neuberger T, Burton B, Clark H, Van Goor F . Use of primary cultures of human bronchial epithelial cells isolated from cystic fibrosis patients for the pre-clinical testing of CFTR modulators. Methods Mol Biol. 2011; 741:39-54. DOI: 10.1007/978-1-61779-117-8_4. View

Greaney A, Adams T, Raredon M, Gubbins E, Schupp J, Engler A . Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing. Cell Rep. 2020; 30(12):4250-4265.e6. PMC: 7175071. DOI: 10.1016/j.celrep.2020.03.004. View

Tong Z, Solanki A, Hamilos A, Levy O, Wen K, Yin X . Application of biomaterials to advance induced pluripotent stem cell research and therapy. EMBO J. 2015; 34(8):987-1008. PMC: 4406648. DOI: 10.15252/embj.201490756. View

10.

Johannson K, Vittinghoff E, Lee K, Balmes J, Ji W, Kaplan G . Acute exacerbation of idiopathic pulmonary fibrosis associated with air pollution exposure. Eur Respir J. 2013; 43(4):1124-31. PMC: 5555605. DOI: 10.1183/09031936.00122213. View

11.

de Hilster R, Sharma P, Jonker M, White E, Gercama E, Roobeek M . Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue. Am J Physiol Lung Cell Mol Physiol. 2020; 318(4):L698-L704. PMC: 7191637. DOI: 10.1152/ajplung.00451.2019. View

12.

Rawlins E, Okubo T, Xue Y, Brass D, Auten R, Hasegawa H . The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell. 2009; 4(6):525-34. PMC: 2730729. DOI: 10.1016/j.stem.2009.04.002. View

13.

Sun X, Sui H, Fisher J, Yan Z, Liu X, Cho H . Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis. J Clin Invest. 2010; 120(9):3149-60. PMC: 2929732. DOI: 10.1172/JCI43052. View

14.

. Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2020; 8(6):585-596. PMC: 7284317. DOI: 10.1016/S2213-2600(20)30105-3. View

15.

Kloxin A, Benton J, Anseth K . In situ elasticity modulation with dynamic substrates to direct cell phenotype. Biomaterials. 2009; 31(1):1-8. PMC: 2791128. DOI: 10.1016/j.biomaterials.2009.09.025. View

16.

Ghaedi M, Niklason L . Human Pluripotent Stem Cells (iPSC) Generation, Culture, and Differentiation to Lung Progenitor Cells. Methods Mol Biol. 2016; 1576:55-92. PMC: 5976544. DOI: 10.1007/7651_2016_11. View

17.

Rock J, Onaitis M, Rawlins E, Lu Y, Clark C, Xue Y . Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A. 2009; 106(31):12771-5. PMC: 2714281. DOI: 10.1073/pnas.0906850106. View

18.

Lavelle G, White M, Browne N, McElvaney N, Reeves E . Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences. Biomed Res Int. 2016; 2016:5258727. PMC: 4908263. DOI: 10.1155/2016/5258727. View

19.

Jacob A, Morley M, Hawkins F, McCauley K, Jean J, Heins H . Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells. Cell Stem Cell. 2017; 21(4):472-488.e10. PMC: 5755620. DOI: 10.1016/j.stem.2017.08.014. View

20.

Gilpin S, Ren X, Okamoto T, Guyette J, Mou H, Rajagopal J . Enhanced lung epithelial specification of human induced pluripotent stem cells on decellularized lung matrix. Ann Thorac Surg. 2014; 98(5):1721-9. PMC: 4252658. DOI: 10.1016/j.athoracsur.2014.05.080. View