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Stem cell-based Lung-on-Chips: The best of both worlds?

ABSTRACT: Pathologies of the respiratory system such as lung infections, chronic inflammatory lung diseases, and lung cancer are among the leading causes of morbidity and mortality, killing one in six people worldwide. Development of more effective treatments is hindered by the lack of preclinical models of the human lung that can capture the disease complexity, highly heterogeneous disease phenotypes, and pharmacokinetics and pharmacodynamics observed in patients. The merger of two novel technologies, Organs-on-Chips and human stem cell engineering, has the potential to deliver such urgently needed models. Organs-on-Chips, which are microengineered bioinspired tissue systems, recapitulate the mechanochemical environment and physiological functions of human organs while concurrent advances in generating and differentiating human stem cells promise a renewable supply of patient-specific cells for personalized and precision medicine. Here, we discuss the challenges of modeling human lung pathophysiology in vitro, evaluate past and current models including Organs-on-Chips, review the current status of lung tissue modeling using human pluripotent stem cells, explore in depth how stem-cell based Lung-on-Chips may advance disease modeling and drug testing, and summarize practical consideration for the design of Lung-on-Chips for academic and industry applications.

SUBMITTER: Nawroth JC

PROVIDER: S-EPMC7172977 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Stem cell-based Lung-on-Chips: The best of both worlds?

Nawroth Janna C JC Barrile Riccardo R Conegliano David D van Riet Sander S Hiemstra Pieter S PS Villenave Remi R

Advanced drug delivery reviews 20180725

Pathologies of the respiratory system such as lung infections, chronic inflammatory lung diseases, and lung cancer are among the leading causes of morbidity and mortality, killing one in six people worldwide. Development of more effective treatments is hindered by the lack of preclinical models of the human lung that can capture the disease complexity, highly heterogeneous disease phenotypes, and pharmacokinetics and pharmacodynamics observed in patients. The merger of two novel technologies, Or ...[more]

PMID: 30009883

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Project description:Abstract Biceps tendinopathy and superior labrum anterior posterior lesions are a common source of shoulder pain and disability and can be effectively treated with biceps tenodesis. There are a variety of open and arthroscopic tenodesis techniques, but no one technique has demonstrated superiority. Arthroscopic techniques often disregard the extra-articular portions of the biceps tendon as a potential source of pain. Open techniques address this concern; however, they can be associated with wound complications, increased blood loss, nerve injury, and disruptions to surgical workflow. Here, we describe an all arthroscopic tenodesis technique at the suprapectoral zone of the tendon. This method addresses extra-articular sources of pain, while limiting the potential pitfalls of open surgery. Technique Video Video 1 Narrated technique video. Standard posterior, anterior, lateral, and low anterior portals are used during the technique. Viewing from the posterior portal in a right shoulder the biceps anchor is debrided to a stable base. A BirdBeak device is inserted through the standard anterior portal and pierces the biceps tendon as laterally as possible, and an 18-gauge spinal needle is used to tease the suture from the BirdBeak device. After a standard subacromial decompression is performed the camera is inserted into the standard lateral portal, and an anterior subdeltoid bursectomy is performed to provide adequate visualization of the tenodesis site. An accessory low anterior portal is created about 1.5 cm proximal to the pectoralis major tendon insertion. The pectoralis major insertion site is used to aid in localization of the tendon just proximal to the subdeltoid portion of the tendon. An 11-blade is inserted through the low anterior portal and used to incise the transverse humeral ligament; the biceps tendon will often bulge from beneath the ligament at this step, confirming appropriate position. The bicep tendon is retracted with the probe, and a noncannulated 8-mm reamer is inserted into the low anterior portal and used to produce a unicortical tunnel. The tunnel’s edges are debrided using an arthroscopic shaver and the arthroscopic electrocautery device; the inferior portion of the tunnel must be smooth to prevent fraying of the tendon. The biceps tendon is then tensioned appropriately via tension pulled through the previously placed suture. A fork-tipped interference screw is then introduced through the low anterior portal to introduce the biceps tendon into the tenodesis site. The interference screw is then inserted and left 1 mm proud. The residual proximal bicep tendon is then amputated using an arthroscopic biter and removed through the lateral portal. The finished tenodesis site is probed and inspected, and a standard postoperative protocol is used.

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Stem cell-based Lung-on-Chips: The best of both worlds?

Publications

Stem cell-based Lung-on-Chips: The best of both worlds?

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