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Review
. 2024 Sep 18;3(6):100201.
doi: 10.1016/j.cellin.2024.100201. eCollection 2024 Dec.

Modeling respiratory tract diseases for clinical translation employing conditionally reprogrammed cells

Danyal Daneshdoust  1 , Kai He  1   2 , Qi-En Wang  1   3 , Jenny Li  1   4 , Xuefeng Liu  1   5
Affiliations
Review

Modeling respiratory tract diseases for clinical translation employing conditionally reprogrammed cells

Danyal Daneshdoust et al. Cell Insight. .

Abstract

Preclinical models serve as indispensable tools in translational medicine. Specifically, patient-derived models such as patient-derived xenografts (PDX), induced pluripotent stem cells (iPSC), organoids, and recently developed technique of conditional reprogramming (CR) have been employed to reflect the host characteristics of diseases. CR technology involves co-culturing epithelial cells with irradiated Swiss-3T3-J2 mouse fibroblasts (feeder cells) in the presence of a Rho kinase (ROCK) inhibitor, Y-27632. CR technique facilitates the rapid conversion of both normal and malignant cells into a "reprogrammed stem-like" state, marked by robust in vitro proliferation. This is achieved without reliance on exogenous gene expression or viral transfection, while maintaining the genetic profile of the parental cells. So far, CR technology has been used to study biology of diseases, targeted therapies (precision medicine), regenerative medicine, and noninvasive diagnosis and surveillance. Respiratory diseases, ranking as the third leading cause of global mortality, pose a significant burden to healthcare systems worldwide. Given the substantial mortality and morbidity rates of respiratory diseases, efficient and rapid preclinical models are imperative to accurately recapitulate the diverse spectrum of respiratory conditions. In this article, we discuss the applications and future potential of CR technology in modeling various respiratory tract diseases, including lung cancer, respiratory viral infections (such as influenza and Covid-19 and etc.), asthma, cystic fibrosis, respiratory papillomatosis, and upper aerodigestive track tumors. Furthermore, we discuss the potential utility of CR in personalized medicine, regenerative medicine, and clinical translation.

Keywords: Asthma; Conditional reprogramming; Covid-19; Cystic fibrosis; Lung cancer; Preclinical models; Respiratory diseases; Respiratory papillomatosis; Respiratory viral infections; Translational medicine.

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Conflict of interest statement

Several patents for CR technology have been awarded to Georgetown University by the US Patent Office. The license for this technology has been given to a Maryland-based start-up company for commercialization. The inventor, X.L., and Georgetown University receive potential royalties and payments from the company. CR media and CR cells have been distributed by Propagenix (acquired by StemCell Technologies), Fisher Scientific, ATCC, etc. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
CR technology has significant applications in respiratory tract disorders. The CR method enables the rapid generation of cultures from both normal and malignant tissue obtained through brushings, swabs, and biopsies. The figure was created using BioRender.
Fig. 2
Fig. 2
|Workflow of human normal airway epithelial cells CRC culture under in vitro apical (ALI) and closed organoids (3D) cultures. The figure was created using BioRender.
Fig. 3
Fig. 3
|Applications of CRCs in respiratory tract diseases. The figure was created using BioRender.
See this image and copyright information in PMC

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