Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells

Hawkins, Finn; Suzuki, Shingo; Beermann, Mary Lou; Barillà, Cristina; Wang, Ruobing; Villacorta‐Martin, Carlos; Berical, Andrew; Jean, Jyh‐Chang; Suer, Jake Le; Matte, Taylor; Simone-Roach, Chantelle; Tang, Yang; Schlaeger, Thorsten M.; Crane, Ana M.; Matthias, Nadine; Huang, Sarah X.L.; Randell, Scott H.; Wu, Joshua H.; Spence, Jason R.; Carraro, Gianni; Stripp, Barry R.; Rab, András; Sorsher, Eric J.; Horani, Amjad; Brody, Steven L.; Davis, Brian R.; Kotton, Darrell N.

doi:10.1016/j.stem.2020.09.017

Cited by 132 publications

(207 citation statements)

References 60 publications

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Section: Identification Of Suitable Regenerative Cells With Differentmentioning

confidence: 99%

“…More recently, iPSCs have been differentiated into basal cells, termed induced basal cells (iBCs) (Hawkins et al, 2020). These iBCs are functionally indistinct from native basal cells and have been shown in vitro to differentiate into a pseudostratified airway epithelium exhibiting CFTR activity (Hawkins et al, 2020). However, the rarer cell types of the epithelium such as the CFTR-expressing ionocytes, and brush cells, were not observed in vitro cultures of iBCs differentiated at air-liquid interface (Hawkins et al, 2020).…”

Section: Identification Of Suitable Regenerative Cells With Differentmentioning

confidence: 99%

“…These iBCs are functionally indistinct from native basal cells and have been shown in vitro to differentiate into a pseudostratified airway epithelium exhibiting CFTR activity (Hawkins et al, 2020). However, the rarer cell types of the epithelium such as the CFTR-expressing ionocytes, and brush cells, were not observed in vitro cultures of iBCs differentiated at air-liquid interface (Hawkins et al, 2020). Furthermore, the long-term effects of these manipulations are not well understood, and several questions regarding the in vivo competence of iBCs remain unanswered.…”

Section: Identification Of Suitable Regenerative Cells With Differentmentioning

confidence: 99%

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Treatment of Cystic Fibrosis: From Gene- to Cell-Based Therapies

et al. 2021

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Prognosis of patients with cystic fibrosis (CF) varies extensively despite recent advances in targeted therapies that improve CF transmembrane conductance regulator (CFTR) function. Despite being a multi-organ disease, extensive lung tissue destruction remains the major cause of morbidity and mortality. Progress towards a curative treatment strategy that implements a CFTR gene addition-technology to the patients’ lungs has been slow and not yet developed beyond clinical trials. Improved delivery vectors are needed to overcome the body’s defense system and ensure an efficient and consistent clinical response before gene therapy is suitable for clinical care. Cell-based therapy–which relies on functional modification of allogenic or autologous cells ex vivo, prior to transplantation into the patient–is now a therapeutic reality for various diseases. For CF, pioneering research has demonstrated proof-of-principle for allogenic transplantation of cultured human airway stem cells into mouse airways. However, applying a cell-based therapy to the human airways has distinct challenges. We review CF gene therapies using viral and non-viral delivery strategies and discuss current advances towards autologous cell-based therapies. Progress towards identification, correction, and expansion of a suitable regenerative cell, as well as refinement of pre-cell transplant lung conditioning protocols is discussed.

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Section: Identification Of Suitable Regenerative Cells With Differentmentioning

confidence: 99%

Section: Identification Of Suitable Regenerative Cells With Differentmentioning

confidence: 99%

Section: Identification Of Suitable Regenerative Cells With Differentmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of Cystic Fibrosis: From Gene- to Cell-Based Therapies

et al. 2021

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“…Investigation of effective methods to differentiate human iPSCs into mature airway epithelium has been crucial to developing functional cells for effective disease modeling and therapeutic screening. iPSCs have been directed to mimic embryonic lung development and differentiate into functional airway epithelium (17,18,27,39,40) through sequential addition of factors that regulate activin/nodal, bone morphogenic protein (BMP), fibroblast growth factor FIGURE 1 | Engineering tissue-informed biomaterials to advance pulmonary regenerative medicine and model respiratory disease. This schematic illustrates the potential for tissue-informed biomaterials to advance pulmonary regenerative medicine through two complementary pathways: (1) by using tissue-informed biomaterial cell culture platforms to differentiate patient-specific stem cells into healthy, implantable lung cells and tissue (left); and (2) engineering biomaterial-based platforms to induce differentiation of these same patient-specific stem cells into diseased phenotypes for disease modeling and evaluation of precision medical treatments (right).…”

Section: Patient-derived Cells For Studying Respiratory Diseasementioning

confidence: 99%

Engineering Tissue-Informed Biomaterials to Advance Pulmonary Regenerative Medicine

et al. 2021

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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.

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“…The large airway epithelium is a pseudostratified columnar epithelium consisting of basal cells in the basal layer, and secretory and ciliated cells residing in an apical/surface layer. Basal cells function as progenitors of other epithelial cells (Boers et al, 1998; Hong et al, 2004a, b; Lynch et al, 2019; Rock et al, 2009) and regulate adhesion of the epithelium to the basement membrane (Evans and Plopper, 1988; Hawkins et al, 2021; Nakajima et al, 1998). Secretory cells can be further divided into two subtypes, club cells and goblet cells.…”

Section: Introductionmentioning

confidence: 99%

Topography-dependent gene expression and function of common cell archetypes in large and small porcine airways

Pezzulo

Thurman

et al. 2021

Preprint

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The small airways of humans are affected early in several lung diseases. However, because they are relatively inaccessible, little is known about the epithelial cells that line these airways. We performed a single cell RNA-seq census of small and large airways of wild-type pigs and pigs with disrupted cystic fibrosis transmembrane conductance regulator (CFTR) gene. The sequencing data showed that small airway epithelia had similar major cell types as large airways but no ionocytes; moreover, lack of CFTR expression had minimal effect on the transcriptome. Small airway epithelial cells expressed a different transcriptome than large airway cells. Quantitative immunohistochemistry showed that small airway basal cells participate in epithelial barrier function. Finally, sequencing data and in vitro electrophysiologic studies suggest that small airway epithelia have a water and ion transport advantage. Our data highlight the archetypal nature of basal, secretory, and ciliated airway cells with location-dependent gene expression and function.

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Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells

Cited by 132 publications

References 60 publications

Treatment of Cystic Fibrosis: From Gene- to Cell-Based Therapies

Treatment of Cystic Fibrosis: From Gene- to Cell-Based Therapies

Engineering Tissue-Informed Biomaterials to Advance Pulmonary Regenerative Medicine

Topography-dependent gene expression and function of common cell archetypes in large and small porcine airways

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