Creating an Artificial 3-Dimensional Ovarian Follicle Culture System Using a Microfluidic System

Healy, M.W.; Dolitsky, Shelley; Villancio-Wolter, Maria K.; Raghavan, Meera; Tillman, Alexandra R.; Morgan, Nicole Y.; DeCherney, Alan H.; Park, Solji; Wolff, E

doi:10.3390/mi12030261

Cited by 12 publications

(9 citation statements)

References 55 publications

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“…Interestingly, the results obtained indicated that the relative expression levels of each specific gene vs. all the other genes considered was maintained for all of the engrafting period. Although further studies are needed to better elucidate this aspect, it is tempting to speculate that, different from what was reported for 2D culture systems where a poor correlation with in vivo conditions was detected [40,41], the decellularized ECM-based scaffold niche may provide repopulating cells with inputs that preserve the transcription regulatory mechanisms at work in their native tissue, offering an adequate 3D microenvironment driving repopulating cells. This hypothesis found further support in the results obtained when ECM-based scaffolds were repopulated with epigenetically erased cells obtained through epigenetic erasing [30][31][32][33][34][35][36][37][42][43][44][45][46][47].…”

Section: Discussionmentioning

confidence: 71%

Ovarian Decellularized Bioscaffolds Provide an Optimal Microenvironment for Cell Growth and Differentiation In Vitro

Pennarossa

Iorio

Gandolfi

et al. 2021

Cells

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Ovarian failure is the most common cause of infertility. Although numerous strategies have been proposed, a definitive solution for recovering ovarian functions and restoring fertility is currently unavailable. One innovative alternative may be represented by the development of an “artificial ovary” that could be transplanted in patients for re-establishing reproductive activities. Here, we describe a novel approach for successful repopulation of decellularized ovarian bioscaffolds in vitro. Porcine whole ovaries were subjected to a decellularization protocol that removed the cell compartment, while maintaining the macrostructure and microstructure of the original tissue. The obtained bioscaffolds were then repopulated with porcine ovarian cells or with epigenetically erased porcine and human dermal fibroblasts. The results obtained demonstrated that the decellularized extracellular matrix (ECM)-based scaffold may constitute a suitable niche for ex vivo culture of ovarian cells. Furthermore, it was able to properly drive epigenetically erased cell differentiation, fate, and viability. Overall, the method described represents a powerful tool for the in vitro creation of a bioengineered ovary that may constitute a promising solution for hormone and fertility restoration. In addition, it allows for the creation of a suitable 3D platform with useful applications both in toxicological and transplantation studies.

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Section: Discussionmentioning

confidence: 71%

Ovarian Decellularized Bioscaffolds Provide an Optimal Microenvironment for Cell Growth and Differentiation In Vitro

Pennarossa

Iorio

Gandolfi

et al. 2021

Cells

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“…Recent studies have demonstrated the efficacy of microfluidic chips in the culturing of single human preantral follicles, with results comparable to those obtained through traditional methods [ 124 ], which is shown in Fig. 2 c Furthermore, the application of this technology in constructing double-layer follicles composed of mouse granulosa cells has yielded promising results, with the resulting follicles exhibiting endocrine function such as the production of estradiol, progesterone, and androstenedione [ 125 ]. Microfluidic chips also have the potential to be integrated with other human organ chips to construct an integrated human body model, so as to better study the endocrine, immune, metabolic and other factors involved in follicular development [ 123 ], as shown in Fig.…”

Section: Ovarian Research Using Microfluidic Systemsmentioning

confidence: 84%

Revolutionizing the female reproductive system research using microfluidic chip platform

Yan,

Wu,

Zhang

et al. 2023

J Nanobiotechnol

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Comprehensively understanding the female reproductive system is crucial for safeguarding fertility and preventing diseases concerning women's health. With the capacity to simulate the intricate physio- and patho-conditions, and provide diagnostic platforms, microfluidic chips have fundamentally transformed the knowledge and management of female reproductive health, which will ultimately promote the development of more effective assisted reproductive technologies, treatments, and drug screening approaches. This review elucidates diverse microfluidic systems in mimicking the ovary, fallopian tube, uterus, placenta and cervix, and we delve into the culture of follicles and oocytes, gametes’ manipulation, cryopreservation, and permeability especially. We investigate the role of microfluidics in endometriosis and hysteromyoma, and explore their applications in ovarian cancer, endometrial cancer and cervical cancer. At last, the current status of assisted reproductive technology and integrated microfluidic devices are introduced briefly. Through delineating the multifarious advantages and challenges of the microfluidic technology, we chart a definitive course for future research in the woman health field. As the microfluidic technology continues to evolve and advance, it holds great promise for revolutionizing the diagnosis and treatment of female reproductive health issues, thus propelling us into a future where we can ultimately optimize the overall wellbeing and health of women everywhere. Graphical Abstract

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“…When integrating with microfluidic chips, the decellularization and recellularization manipulation can be reproduced directly in the devices or used as medium to fill the chips ( Hong et al , 2017 ; Palikuqi et al , 2020 ; Bhatt et al , 2022 ). The latter provides a dynamic stimulus to the cumulus cell–oocyte complex or denuded oocytes, which improves the outcomes of oocyte maturation and IVF ( Nagashima et al , 2018 ; Podwin et al , 2020 ; Healy et al , 2021 ; Sadeghzadeh Oskouei et al , 2021 ). Altogether, the integration of these advanced culture systems will facilitate the development of ovarian regeneration and drug-testing models.…”

Section: Discussionmentioning

confidence: 99%

Extracellular matrix-derived scaffolds in constructing artificial ovaries for ovarian failure: a systematic methodological review

Huang

Yan

et al. 2023

Human Reproduction Open

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STUDY QUESTION What is the current state-of-the-art methodology assessing decellularized extracellular matrix (dECM)-based artificial ovaries for treating ovarian failure? SUMMARY ANSWER Preclinical studies have demonstrated that decellularized scaffolds support the growth of ovarian somatic cells and follicles both in vitro and in vivo. WHAT IS KNOWN ALREADY Artificial ovaries are a promising approach for rescuing ovarian function. Decellularization has been applied in bioengineering female reproductive tract tissues. However, decellularization targeting the ovary lacks a comprehensive and in-depth understanding. STUDY DESIGN, SIZE, DURATION PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials were searched from inception until October 20, 2022 to systematically review all studies in which artificial ovaries were constructed using decellularized extracellular matrix scaffolds. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. PARTICIPANTS/MATERIALS, SETTING, METHODS Two authors selected studies independently based on the eligibility criteria. Studies were included if decellularized scaffolds, regardless of their species origin, were seeded with ovarian cells or follicles. Review articles and meeting papers were removed from the search results, as were articles without decellularized scaffolds or recellularization or decellularization protocols, or control groups or ovarian cells. MAIN RESULTS AND THE ROLE OF CHANCE The search returned a total of 754 publications, and 12 papers were eligible for final analysis. The papers were published between 2015 and 2022, and were most frequently reported as coming from Iran. Detailed information on the decellularization procedure, evaluation method and preclinical study design was extracted. In particular, we concentrated on the type and duration of detergent reagent, DNA and extracellular matrix detection methods, and the main findings on ovarian function. Decellularized tissues derived from humans and experimental animals were reported. Scaffolds loaded with ovarian cells have produced estrogen and progesterone, though with high variability, and have supported the growth of various follicles. Serious complications have not been reported. LIMITATIONS, REASONS FOR CAUTION A meta-analysis could not be performed. Therefore, only data pooling was conducted. Additionally, the quality of some studies was limited mainly due to incomplete description of methods, which impeded specific data extraction and quality analysis. Several studies that used dECM scaffolds were performed or authored by the same research group with a few modifications, which might have biased our evaluation. WIDER IMPLICATIONS OF THE FINDINGS Overall, the decellularization-based artificial ovary is a promising but experimental choice for substituting insufficient ovaries. A generic and comparable standard should be established for the decellularization protocols, quality implementation, and cytotoxicity controls. Currently, decellularized materials are far from being clinically applicable to artificial ovaries. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the National Natural Science Foundation of China (Nos. 82001498 and 81701438). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER This systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO, ID CRD42022338449).

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Creating an Artificial 3-Dimensional Ovarian Follicle Culture System Using a Microfluidic System

Cited by 12 publications

References 55 publications

Ovarian Decellularized Bioscaffolds Provide an Optimal Microenvironment for Cell Growth and Differentiation In Vitro

Ovarian Decellularized Bioscaffolds Provide an Optimal Microenvironment for Cell Growth and Differentiation In Vitro

Revolutionizing the female reproductive system research using microfluidic chip platform

Extracellular matrix-derived scaffolds in constructing artificial ovaries for ovarian failure: a systematic methodological review

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