Modeling mucus physiology and pathophysiology in human organs-on-chips

Izadifar, Zohreh; Sontheimer-Phelps, Alexandra; Lubamba, Bob; Bai, Haiqing; Fadel, Cicely; Stejskalová, Anna; Özkan, Aliçan; Dasgupta, Queeny; Bein, Amir; Junaid, Abidemi; Gulati, Aakanksha; Mahajan, Gautam; Kim, Seong–Min; LoGrande, Nina; Naziripour, Arash; Ingber, Donald E.

doi:10.1016/j.addr.2022.114542

Cited by 15 publications

(11 citation statements)

References 227 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cervical mucus is composed of 92%–95% water and ions and 5%–8% solid matter 114 . However, it cannot be recapitulated by conventional cervicovaginal culture models 115 . With the help of the microfluidic technique, Izadifar et al successfully developed a human cervix chip that could produce abundant amounts of mucus, mimicking the natural one biomechanically and biochemically 115 .…”

Section: Discussionmentioning

confidence: 99%

“…However, it cannot be recapitulated by conventional cervicovaginal culture models 115 . With the help of the microfluidic technique, Izadifar et al successfully developed a human cervix chip that could produce abundant amounts of mucus, mimicking the natural one biomechanically and biochemically 115 . A cervix chip could also be fabricated by culturing cervical epithelial cells on the mucus chips 116 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Microfluidic chip as a promising evaluation method in assisted reproduction: A systematic review

Wu,

Yan

et al. 2023

Bioengineering & Transla Med

View full text Add to dashboard Cite

The aim of assisted reproductive technology (ART) is to select the high‐quality sperm, oocytes, and embryos, and finally achieve a successful pregnancy. However, functional evaluation is hindered by intra‐ and inter‐operator variability. Microfluidic chips emerge as the one of the most powerful tools to analyze biological samples for reduced size, precise control, and flexible extension. Herein, a systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and IEEE Xplore databases until March 2023. We displayed and prospected all detection strategies based on microfluidics in the ART field. After full‐text screening, 71 studies were identified as eligible for inclusion. The percentages of human and mouse studies equaled with 31.5%. The prominent country in terms of publication number was the USA (n = 13). Polydimethylsiloxane (n = 49) and soft lithography (n = 28) were the most commonly used material and fabrication method, respectively. All articles were classified into three types: sperm (n = 38), oocytes (n = 20), and embryos (n = 13). The assessment contents included motility, counting, mechanics, permeability, impedance, secretion, oxygen consumption, and metabolism. Collectively, the microfluidic chip technology facilitates more efficient, accurate, and objective evaluation in ART. It can even be combined with artificial intelligence to assist the daily activities of embryologists. More well‐designed clinical studies and affordable integrated microfluidic chips are needed to validate the safety, efficacy, and reproducibility.Trial registration: The protocol was registered in the Open Science Frame REGISTRIES (identification: osf.io/6rv4a).

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Microfluidic chip as a promising evaluation method in assisted reproduction: A systematic review

Wu,

Yan

et al. 2023

Bioengineering & Transla Med

View full text Add to dashboard Cite

show abstract

“…The mucus layer in the FRT is vital for reproductive functions, with its properties varying due to hormonal changes, ensuring a conducive environment for fertilization and embryo gestation. 98 The cervico-vaginal tract acts as a barrier, balancing sperm passage, supporting beneficial bacteria, and warding off harmful pathogens. 99,100 Disturbances, like bacterial vaginosis, can cause health issues such as preterm birth and increased HIV-1 risk.…”

Section: Modeling the Mucus Layermentioning

confidence: 99%

“…However, these models have limitations, and human organ-on-a-chip technology has been applied to overcome these challenges and model mucus biology more physiologically. 98 One notable advancement was made by Izadifar et al, who developed a two-channel cervical chip lined with primary human cervical ECs. 18 This innovation, along with the human vaginal chip, has provided insights into mucus physiology and pathophysiology.…”

Section: Modeling the Mucus Layermentioning

confidence: 99%

“…107 Organ-on-a-chip technology's potential extends beyond modeling, facilitating simultaneous characterization of mucus biochemical, structural, and biophysical properties. 98 For future research, it would be useful to see if such FRT organoids-on-a-chip models can be made using organoid-derived cells or linearized organoids to have an accessible mucus layer. Then the properties between the differently constructed models' mucus layers could be assessed, both with microbial cultures and without.…”

Section: Modeling Specific Properties Of the Frtmentioning

confidence: 99%

See 1 more Smart Citation

Advanced Technologies for Studying Microbiome–Female Reproductive Tract Interactions: Organoids, Organoids-on-a-Chip, and Beyond

Kaya,

de Zoete,

Steba

2023

Semin Reprod Med

View full text Add to dashboard Cite

The female reproductive tract (FRT) is home to diverse microbial communities that play a pivotal role in reproductive health and disorders such as infertility, endometriosis, and cervical cancer. To understand the complex host–microbiota interactions within the FRT, models that authentically replicate the FRT's environment, including the interplay between the microbiota, mucus layer, immune system, and hormonal cycle, are key. Recent strides in organoid and microfluidic technologies are propelling research in this domain, offering insights into FRT–microbiota interactions and potential therapeutic avenues. This review delves into the current state of FRT organoid models and microbe integration techniques, evaluating their merits and challenges for specific research objectives. Emphasis is placed on innovative approaches and applications, including integrating organoids with microfluidics, and using patient-derived biobanks, as this offers potential for deeper mechanistic insights and personalized therapeutic strategies. Modeling various FRT properties in organoids is explored, from encompassing age-related epithelial features, oxygen levels, and hormonal effects to mucus layers, immune responses, and microbial interactions, highlighting their potential to transform reproductive health research and predict possible outcomes.

show abstract

A Dopamine‐Modified Hyaluronic Acid‐Based Mucus Carrying Phytoestrogen and Urinary Exosome for Thin Endometrium Repair

Li,

Tan,

Deng

et al. 2024

Advanced Materials

View full text Add to dashboard Cite

Thin endometrium (TE) is closely associated with infertility in reproductive medicine. Estrogen therapy gains unsatisfactory outcomes. In this study, an artificial mucus based on dopamine (L‐DOPA)‐modified hyaluronic acid combining phytoestrogen cajaninstilbene acid and rat urinary exosomes (CUEHD) is constructed for TE treatment using a rat TE model. In the rat TE model, the dominant elastic behavior and adhesive properties of CUEHD guarantee adequate retention, rendering superior synergistic treatment efficacy and favorable biosafety characteristics. CUEHD treatment significantly increases endometrial thickness and promotes receptivity and fertility. Mechanistically, estrogen homeostasis, inflammation inhibition, and endometrial regeneration are achieved through the crosstalk between ER‐NLRP3‐IL1β and Wnt‐β catenin‐TGFβ‐smad signaling pathways. Moreover, the therapeutic potential of exosomes from human urine and adipose tissue‐derived stem cells (ADSCs) and rat ADSCs are also demonstrated, indicating extensive use of the artificial mucus system. Thus, this study illustrates a platform combining phytoestrogen and exosomes with promising implications for TE treatment.

show abstract

Modeling mucus physiology and pathophysiology in human organs-on-chips

Cited by 15 publications

References 227 publications

Microfluidic chip as a promising evaluation method in assisted reproduction: A systematic review

Microfluidic chip as a promising evaluation method in assisted reproduction: A systematic review

Advanced Technologies for Studying Microbiome–Female Reproductive Tract Interactions: Organoids, Organoids-on-a-Chip, and Beyond

A Dopamine‐Modified Hyaluronic Acid‐Based Mucus Carrying Phytoestrogen and Urinary Exosome for Thin Endometrium Repair

Contact Info

Product

Resources

About