Organoids as a model system for studying human lung development and disease

Nadkarni, Rohan R.; Abed, Soumeya; Draper, Jonathan S.

doi:10.1016/j.bbrc.2015.12.091

Cited by 86 publications

(61 citation statements)

References 80 publications

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“…Organoids can be generated from multiple cell types and generally self-aggregate into three dimensional structures that can mimic the organization of the native organ (Rock, Onaitis et al 2009, Sato, Vries et al 2009, Barker, Huch et al 2010, Barkauskas, Cronce et al 2013, Nadkarni, Abed et al 2016). In the lung, the source of cells used in organoids can include primary cells from human or mouse lungs or cells derived from differentiated pluripotent stem cells.…”

Section: Modeling Lung Disease and Regenerationmentioning

confidence: 99%

Developmental pathways in lung regeneration

Stabler

Morrisey

2016

Cell Tissue Res

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The key processes of lung development have been elucidated in the past several decades, helping to identify and characterize the resident progenitor cells that ultimately generate the mature organ. The adult lung is a complex organ consisting of scores of different cell lineages that are remarkably quiescent in the absence of injury. Despite low cellular turnover, the lung can respond quickly and dramatically to acute damage when spatially restricted stem and progenitor cells re-enter the cell cycle and differentiate to promote repair. The findings from lung developmental biology are now being used to examine the mechanisms that underlie lung regeneration. The use of in vitro models such as pluripotent stem cells and new methods of gene editing have provided models for understanding lung disease, exploring the mechanisms of lung regeneration, and have raised the prospect of correcting lung dysfunction. We will outline how basic studies into lung developmental biology are now being applied to lung regeneration, opening up new avenues of research that may ultimately be harnessed for treatments of lung disease.

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Section: Modeling Lung Disease and Regenerationmentioning

confidence: 99%

Developmental pathways in lung regeneration

Stabler

Morrisey

2016

Cell Tissue Res

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“…More accurately, organoids [i] contain more than one cell type, [ii] show physiological function of the organ they model, and [iii] are formed by self-assembly of cells and show organization of the specific organ [90,91]. The present models arose with the introduction of the hanging drop method by Harrison in 1906 [20] and Wilson who showed self-organization of sponge cells forming a whole organism [92].…”

Section: Outlook: Skin Organoids and Their Potential Use For Personalmentioning

confidence: 99%

In vitro skin three-dimensional models and their applications

Klicks

Molitor

Ertongur-Fauth

et al. 2017

JCB

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Abstract. Skin fulfils a plethora of eminent physiological functions ranging from physical barrier over immunity shield to the interface mediating social interaction. Prone to several acquired and inherited diseases, skin is therefore a major target of pharmaceutical and cosmetic research. The lack of similarity between human and animal skin and rising ethical concerns in the use of animal models have driven the search for novel realistic three-dimensional skin models. This review provides a survey of contemporary skin models and compares them in terms of applicability, reliability, cost and complexity.Keywords: Skin, phenotypic screening, 3D models, pharmaceutical research Skin -composition and functionHuman skin covers an area of almost 2 m 2 in the adult and consists of the three major layers, subcutis, dermis, and epidermis. The subcutis is composed of adipose and epithelial cells. It harbours blood vessels, neurites of peripheral neurons, Vater-Pacini mechanosensors, and, partially, also sweat glands and hair follicles. It connects the skin to periosteum and fascia, absorbs forces, and mediates thermal insulation. The dermis supplies the epidermis with mechanical support and nutrients. It is stratified into an inner, reticular, and an outer, papillary, zone. The dermis houses most sebaceous glands, sweat glands, hair follicles, smooth muscle cells, and capillary beds and, thus, regulates skin moisture, body temperature, and performs the secretory function of skin. The papillary layer is characterized by relatively loose connective tissue, where Meissner corpuscles sense touch. Immune cells, particularly mast cells and dendritic cells, are patrolling in the papillary layer and mediate local inflammatory reactions and immune surveillance. Finally, dermal fibroblasts secrete extracellular matrix (ECM) and basement membrane components. These are primarily collagens I and III, and a proteoglycan-rich ground substance [1]. The resulting ECM mediates tensile strength of the dermis. The dermo-epidermal junction is centered around a special basement membrane. This is composed of a laminin/collagen IV scaffold and further typical basement membrane components such as perlecans and nidogens [1].The epidermis is a squamous epithelium of 50-100 m thickness. It is devoid of blood vessels but contains keratinocytes, Merkel cell mechanosensors, Langerhans immune cells, and melanocytes. The 1 These authors contributed equally.

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“…While these platforms are primarily used to look at lung development and disease, there may be unique opportunities for use with pathogens. Of note, for further reading in the use of lung organoid systems, Nadkami at co-authors provide an informative review [48]. As additional technologies, such as the popularized lung-on-a-chip [49,50], are being established, and even the recent report of closed circulatory perfusion systems that includes a liver-heart-lung cell platform [51], scientists are now being enticed with next-generation platforms to study respiratory pathogens.…”

Section: Future Directions and Considerationsmentioning

confidence: 99%

Advances and Remaining Challenges in the Study of Influenza and Anthrax Infection in Lung Cell Culture

Powell

Straub

2018

Challenges

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For over 30 years, immortalized lung cells have enabled researchers to elucidate lung-pathogen molecular interactions. However, over the last five years, numerous commercial companies are now providing affordable, ready-to-use primary lung cells for use in research laboratories. Despite advances in primary cell culture, studies using immortalized lung cells still dominate the recent scientific literature. In this review, we highlight recent influenza and anthrax studies using in vitro primary lung tissue models and how these models are providing better predictive outcomes for when extrapolated to in vivo observations. By focusing on one virus (influenza) and one bacterium (Bacillus anthracis), it is the intent that these primary lung cell culture observations may translate into more useful studies for other related viral and bacterial lung pathogens of interest.

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Organoids as a model system for studying human lung development and disease

Cited by 86 publications

References 80 publications

Developmental pathways in lung regeneration

Developmental pathways in lung regeneration

In vitro skin three-dimensional models and their applications

Advances and Remaining Challenges in the Study of Influenza and Anthrax Infection in Lung Cell Culture

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