3D Human Organoids: The Next “Viral” Model for the Molecular Basis of Infectious Diseases

Chia, Shirley Pei Shan; Kong, Sharleen Li Ying; Soh, Boon Seng

doi:10.3390/biomedicines10071541

Cited by 12 publications

(7 citation statements)

References 165 publications

(251 reference statements)

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“…Organoids are generated using different techniques, as such there is no specific protocol on the generation of organoids that has been developed. The morphological development of organoids may be restricted by naturally produced ECMs like Matrigel due to batch-to-batch variability and the presence of animal-derived products [ 143 , 144 ].…”

Section: Limitations Of Organoid Applicationmentioning

confidence: 99%

Insights on Three Dimensional Organoid Studies for Stem Cell Therapy in Regenerative Medicine

Mulaudzi,

Abrahamse,

Crous

2023

Stem Cell Rev and Rep

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Regenerative medicine has developed as a promising discipline that utilizes stem cells to address limitations in traditional therapies, using innovative techniques to restore and repair damaged organs and tissues. One such technique is the generation of three-dimensional (3D) organoids in stem cell therapy. Organoids are 3D constructs that resemble specific organs' structural and functional characteristics and are generated from stem cells or tissue-specific progenitor cells. The use of 3D organoids is advantageous in comparison to traditional two-dimensional (2D) cell culture by bridging the gap between in vivo and in vitro research. This review aims to provide an overview of the advancements made towards regenerative medicine using stem cells to generate organoids, explore the techniques used in generating 3D organoids and their applications and finally elucidate the challenges and future directions in regenerative medicine using 3D organoids. Graphical Abstract

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Section: Limitations Of Organoid Applicationmentioning

confidence: 99%

Insights on Three Dimensional Organoid Studies for Stem Cell Therapy in Regenerative Medicine

Mulaudzi,

Abrahamse,

Crous

2023

Stem Cell Rev and Rep

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“…The main organoid models we have focused on are similar and include lung and brain organoids. The virus invasion mechanism is the most common focus in this field of research and has been the predominant focus of all previous reviews [ 23 , 24 , 26 ]. This review differs, however, for the following reasons: (1) we have summarised novel organoid models that have not been mentioned in previous reviews, such as the skin, salivary, and nasal organoid models; (2) we have summarised the limitations of the organoid models and the problems encountered in previous organoid cultures and have provided advice to help address these issues in future investigations; (3) we have described the applications of organoids in tracing the origins, mutations, and species specificity of SARS-CoV-2, thus providing a novel angle for SARS-CoV-2 studies; and (4) we have also discussed the different organoid culture methods and compared them to determine the most suitable culture environment.…”

Section: Low Degree Of Organ Systematisationmentioning

confidence: 99%

“…A brain organoid was also used for the study of prion diseases, where it showed immune responses and individualized pathology changes with prion challenging. In addition, changes in cellular metabolism and cytokine secretion were also observed [ 26 ]. Holthaus et al found that the cAMP/PKA signalling pathway was the main pathway involved in the damage of the intestinal epithelium barrier, as a result of infection by Giardia duodenalis [ 27 ].…”

Section: Brief Introduction To Organoidsmentioning

confidence: 99%

Organoids to Remodel SARS-CoV-2 Research: Updates, Limitations and Perspectives

An¹,

He²,

Ge³

et al. 2023

Aging and disease

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The novel COVID-19 pneumonia caused by the SARS-CoV-2 virus poses a significant threat to human health. Scientists have made significant efforts to control this virus, consequently leading to the development of novel research methods. Traditional animal and 2D cell line models might not be suitable for large-scale applications in SARS-CoV-2 research owing to their limitations. As an emerging modelling method, organoids have been applied in the study of various diseases. Their advantages include their ability to closely mirror human physiology, ease of cultivation, low cost, and high reliability; thus, they are considered to be a suitable choice to further the research on SARS-CoV-2. During the course of various studies, SARS-CoV-2 was shown to infect a variety of organoid models, exhibiting changes similar to those observed in humans. This review summarises the various organoid models used in SARS-CoV-2 research, revealing the molecular mechanisms of viral infection and exploring the drug screening tests and vaccine research that have relied on organoid models, hence illustrating the role of organoids in remodelling SARS-CoV-2 research.

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“…The recent development of organoids, self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function, provides robust models to study infections directly in fully differentiated human tissues 27 . Originally established for gastrointestinal tissue 28 , several models are now available, including bladder 29 , pancreas 30 , liver 31 as well as upper 32 and lower 33 airways.…”

Section: Introductionmentioning

confidence: 99%

Goblet cell invasion promotes breaching of respiratory epithelia by an opportunistic human pathogen

Swart,

Laventie,

Sütterlin

et al. 2023

Preprint

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While commensal bacteria generally respect natural barriers of the human body, pathogens are able to breach epithelia, invade deeper tissue layers and cause life-threatening infections. Pseudomonas aeruginosa, an opportunistic human pathogen, is a leading cause of severe hospital-acquired pneumonia, with mortality rates as high as 50% in mechanically ventilated patients. Effective colonization and breaching of lung mucosa are hallmarks of P. aeruginosa pathogenesis. Although virulence factors and behavioral strategies of P. aeruginosa have been described, it has remained unclear how this pathogen disseminates on functional mucosal surfaces, how it avoids mucociliary clearance and how it invades the tissue barrier. Using fully differentiated human lung epithelia, we demonstrate that P. aeruginosa efficiently spreads on the apical tissue surface before it breaches epithelia by specifically invading mucus secreting goblet cells. Internalization leads to host cell death and expulsion and the formation of ruptures of the epithelial barrier. Rupture sites are rapidly colonized by extracellular bacteria through active chemotaxis, leading to increasing tissue damage and successful pathogen translocation to the unprotected basolateral side of the epithelium. We show that cell invasion is promoted by two Type-6 toxin secretion systems (T6SS), while Type-3 (T3SS) mediates cell death of infected goblet cells. T3SS mutants invade goblet cells normally, but internalized bacteria fail to trigger goblet cell expulsion and instead show unrestrained intracellular replication. While the effective shedding of infected host cells reveals potent tissue protection mechanisms, the discovery of an intracellular lifestyle of P. aeruginosa in human lung epithelia provides new entry points into investigating the intersection of antibiotic and immune mechanisms during lung infections. By demonstrating that P. aeruginosa uses a combination of specific virulence factors and collective behavior to invade goblet cells and breach the lung tissue barrier from within, these studies reveal novel mechanisms underlying lung infection dynamics under physiological conditions.

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3D Human Organoids: The Next “Viral” Model for the Molecular Basis of Infectious Diseases

Cited by 12 publications

References 165 publications

Insights on Three Dimensional Organoid Studies for Stem Cell Therapy in Regenerative Medicine

Insights on Three Dimensional Organoid Studies for Stem Cell Therapy in Regenerative Medicine

Organoids to Remodel SARS-CoV-2 Research: Updates, Limitations and Perspectives

Goblet cell invasion promotes breaching of respiratory epithelia by an opportunistic human pathogen

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