Probing Embryonic Stem Cell Autocrine and Paracrine Signaling Using Microfluidics

Przybyla, Laralynne; Voldman, Joel

doi:10.1146/annurev-anchem-062011-143122

Cited by 68 publications

(77 citation statements)

References 106 publications

(137 reference statements)

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“…Microfluidics with patterning and temporal analysis PSC Reveal paracrine/autocrine signaling for PSC self-renewal [110] Microbioreactor array with 3-D cell culture setting EBs derived from human ESC or iPSC PSC mesoderm differentiation, with controlled cytokine gradients.…”

Section: Understanding Of Cell Migration and Cancer Invasion [104]mentioning

confidence: 99%

“…For examples, MSCs secreted various trophic factors to modulate the immune response and cell survival [107] . PSCs have also been shown to self-regulate the expansion and differentiation through autocrine/paracrine signaling such as Wnt, lefty, and Activin A [108][109][110][111][112] . For hematopoietic differentiation, the secreted VEGF, stem cell factor (SCF) and anti-apoptotic factors from ESCs stimulated the formation of colony-forming cells [113] .…”

Section: Outlet Portsmentioning

confidence: 99%

“…By increasing the flow rate to wash out the endogenous secreted factors, PSC spontaneous differentiation occurred [108,115] . While microfluidics has been explored to study the autocrine/ paracrine signaling of adherent stem cells [108,110] , its use in suspension stem cells is also possible in combination with other approaches such as pathway inhibition and fedbatch dilutio [110,116] . Cell communication and spatial ligand distribution in 3-D suspended cells are determined by cell organization, cell density and ligand diffusivity.…”

Section: Outlet Portsmentioning

confidence: 99%

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Engineering stem cell niches in bioreactors

Liu

Liu²,

Zang³

et al. 2013

WJSC

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Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as "niches", to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/ autocrine signaling and physical forces (i.e. , mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering.

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Section: Understanding Of Cell Migration and Cancer Invasion [104]mentioning

confidence: 99%

Section: Outlet Portsmentioning

confidence: 99%

Section: Outlet Portsmentioning

confidence: 99%

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Engineering stem cell niches in bioreactors

Liu

Liu²,

Zang³

et al. 2013

WJSC

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“…4,5 In vitro cultured PSCs produce endogenous ECM proteins (i.e., fibronectin [FN], basement membrane proteins) that regulate PSC fate through cell adhesion and/or binding with autocrine factors (i.e., leukemia inhibitory factor [LIF], Wnt, and Activin). [6][7][8][9] Thus, the derivation of ECMs from PSC cultures while preserving their distinct signaling capacities will greatly enhance their potential in cell delivery and tissue repair. 10,11 Stem cell-derived ECMs have been used to support in vitro cell expansion and differentiation as well as in vivo tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Matrices Decellularized from Embryonic Stem Cells Maintained Their Structure and Signaling Specificity

Sart

2014

Tissue Engineering Part A

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Embryonic stem cells (ESCs) emerge as a promising tool for tissue engineering and regenerative medicines due to their extensive self-renewal ability and the capacity to give rise to cells from all three-germ layers. ESCs also secrete a large amount of endogenous extracellular matrices (ECMs), which play an important role in regulating ESC self-renewal, lineage commitment, and tissue morphogenesis. ECMs derived from ESCs have a broader signaling capacity compared to somatic ECMs and are predicted to have a lower risk of tumor formation associated with ESCs. In this study, ECMs from undifferentiated ESC monolayers, undifferentiated aggregates, or differentiated embryoid bodies at different developmental stages and lineage specifications were decellularized and their capacities to direct ESC proliferation and differentiation were characterized. The results demonstrate that the ESC-derived ECMs were able to influence ESC proliferation and differentiation by direct interactions with the cells and by influencing the signaling functions of the regulatory macromolecules such as retinoic acid. Such matrices have the potential to present regulatory signals to direct lineage-and developmentspecific cellular responses for in vitro applications or cell delivery.

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“…For getting more insights, microfluidic systems have been implemented allowing very precise studies on the effects of shear fields/shear stress in conjunction with ECM and medium composition (study of the effects of cytokines, growth factors, etc.) on cell renewal and stem cell fate in view to the development of an optimal culture system for expansion and differentiation of stem cells [124][125][126].…”

mentioning

confidence: 99%

Advances in cell culture: anchorage dependence

Merten

2015

Phil. Trans. R. Soc. B

129

103

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Anchorage-dependent cells are of great interest for various biotechnological applications. (i) They represent a formidable production means of viruses for vaccination purposes at very large scales (in 1000-6000 l reactors) using microcarriers, and in the last decade many more novel viral vaccines have been developed using this production technology. (ii) With the advent of stem cells and their use/potential use in clinics for cell therapy and regenerative medicine purposes, the development of novel culture devices and technologies for adherent cells has accelerated greatly with a view to the large-scale expansion of these cells. Presently, the really scalable systems-microcarrier/ microcarrier-clump cultures using stirred-tank reactors-for the expansion of stem cells are still in their infancy. Only laboratory scale reactors of maximally 2.5 l working volume have been evaluated because thorough knowledge and basic understanding of critical issues with respect to cell expansion while retaining pluripotency and differentiation potential, and the impact of the culture environment on stem cell fate, etc., are still lacking and require further studies. This article gives an overview on critical issues common to all cell culture systems for adherent cells as well as specifics for different types of stem cells in view of small-and large-scale cell expansion and production processes.

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Probing Embryonic Stem Cell Autocrine and Paracrine Signaling Using Microfluidics

Cited by 68 publications

References 106 publications

Engineering stem cell niches in bioreactors

Engineering stem cell niches in bioreactors

Extracellular Matrices Decellularized from Embryonic Stem Cells Maintained Their Structure and Signaling Specificity

Advances in cell culture: anchorage dependence

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