The Microfluidic Environment Reveals a Hidden Role of Self-Organizing Extracellular Matrix in Hepatic Commitment and Organoid Formation of hiPSCs

Michielin, Federica; Giobbe, Giovanni Giuseppe; Luni, Camilla; Hu, Qianjiang; Maroni, Ida; Orford, Michael; Manfredi, Anna; Filippo, Lucio Di; David, Anna L.; Cacchiarelli, Davide; Coppi, Paolo De; Eaton, Simon; Elvassore, Nicola

doi:10.1016/j.celrep.2020.108453

Cited by 28 publications

(19 citation statements)

References 56 publications

(81 reference statements)

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“…By quantitatively analyzing the proteomic composition of conditioned media in microfluidics and in conventional wells (46), they demonstrated that the highly concentrated microfluidic soluble environment promoted an endogenous ECM and, in particular, collagen I and fibronectin deposition and remodeling. The maturation-promoting role of ECM endogenous composition was then confirmed in an organoid hepatic model (38). The relevance of ECM was shown also in endoderm differentiation toward the intestinal phenotype in a study by Naumovska and colleagues (34).…”

Section: On-chip Differentiation Toward More Mature Phenotypesmentioning

confidence: 84%

“…At the microscale, differentiation has been accomplished according to two complementary biologically inspired strategies (Table 2). The first approach uses microfluidics to mimic the physiological environment during embryonic development and morphogenesis (19,(30)(31)(32)(33)(34)(35)(36)(37)(38). It is based on providing exogenous molecules in the culture medium that sequentially activate the developmental intracellular signaling pathways.…”

Section: Human Pluripotent Stem Cell Differentiation At the Microscalementioning

confidence: 99%

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Derivation and Differentiation of Human Pluripotent Stem Cells in Microfluidic Devices

Luni

Gagliano

Elvassore

2022

Annu. Rev. Biomed. Eng.

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An integrative approach based on microfluidic design and stem cell biology enables capture of the spatial-temporal environmental evolution underpinning epigenetic remodeling and the morphogenetic process. We examine the body of literature that encompasses microfluidic applications where human induced pluripotent stem cells are derived starting from human somatic cells and where human pluripotent stem cells are differentiated into different cell types. We focus on recent studies where the intrinsic features of microfluidics have been exploited to control the reprogramming and differentiation trajectory at the microscale, including the capability of manipulating the fluid velocity field, mass transport regime, and controllable composition within micro- to nanoliter volumes in space and time. We also discuss studies of emerging microfluidic technologies and applications. Finally, we critically discuss perspectives and challenges in the field and how these could be instrumental for bringing about significant biological advances in the field of stem cell engineering. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 24 is June 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: On-chip Differentiation Toward More Mature Phenotypesmentioning

confidence: 84%

Section: Human Pluripotent Stem Cell Differentiation At the Microscalementioning

confidence: 99%

Derivation and Differentiation of Human Pluripotent Stem Cells in Microfluidic Devices

Luni

Gagliano

Elvassore

2022

Annu. Rev. Biomed. Eng.

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“…Recently, Michielin et al [82] have studied the role of accumulative soluble ECM in developing hiPSC-derived hepatic organoids in microfluidic environments (Fig. 4A).…”

Section: Liver Organoids-on-a-chipmentioning

confidence: 99%

Recent advances and challenges in organoid-on-a-chip technology

Suhito

Kim

2022

Organoid

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Conventional 2-dimensional cell culture poorly mimics human-relevant models, which is considered a major challenge in biological research. Organoids are a recent breakthrough in 3-dimensional (3D) in vitro tissue engineering that better reflect the physiological, morphological, and functional properties of in vivo organs (e.g., brain, heart, kidney, lung, and liver). Consequently, organoids are extensively used in various impactful biomedical applications including organ development, disease modeling, and clinical drug testing. However, organoid technology still has several limitations, including low reproducibility, vascularization, limited nutrient uptake and distribution (affecting the level of organoid maturation), lack of standardization, and intra-clonal variability. Efforts have been made to overcome these shortcomings of organoid culture. Microfluidic technology has successfully facilitated the establishment of organoid-on-a-chip systems, which effectively improve the structural and physiological features of organoids in a controlled manner. This review discusses the recent advances and developments in organoid-on-a-chip technology. We hope that this study will motivate researchers to explore the possible engagement between microfluidic devices and self-assembled 3D cell cultures to leverage the enhanced quality of organoids, which will have favorable impacts on future tissue regeneration and regenerative therapies.

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“…On the other hand, microfluidic systems are devices that handle few microliters of medium within micrometric channels [18]. When used for cell culture, they have been demonstrated to establish a different balance between cell-secreted endogenous factors and exogenous factors from the culture medium [19,20], with implications for biological response in multiple applications, such as human somatic cell reprogramming to pluripotency [21][22][23] and differentiation [24,25]. Given that in vivo the interstitial spaces in tissues have dimensions comparable to those of microfluidic systems, a thorough understanding on how extracellular phosphorylation is regulated and its functional implications in physiological and pathological conditions may be better captured in vitro at microscale.…”

Section: Introductionmentioning

confidence: 99%

Extracellular phosphoprotein regulation is affected by culture system scale-down

Xue¹,

Cui²,

Martewicz³

et al. 2022

Biochimica et Biophysica Acta (BBA) - General Subjects

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The Microfluidic Environment Reveals a Hidden Role of Self-Organizing Extracellular Matrix in Hepatic Commitment and Organoid Formation of hiPSCs

Cited by 28 publications

References 56 publications

Derivation and Differentiation of Human Pluripotent Stem Cells in Microfluidic Devices

Derivation and Differentiation of Human Pluripotent Stem Cells in Microfluidic Devices

Recent advances and challenges in organoid-on-a-chip technology

Extracellular phosphoprotein regulation is affected by culture system scale-down

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