Mechanobiology of Human Pluripotent Stem Cells

Earls, Jonathan K.; Jin, Sha; Ye, Kaiming

doi:10.1089/ten.teb.2012.0641

Cited by 26 publications

(18 citation statements)

References 88 publications

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“…Shear stress induced by agitation is also known to play an important role in iPSC differentiation 50,51 . The glass-ball type spinner flask produces laminar flow (Re < 1000) and mild shear rate less than 0.15 N/m 2 36 , while tissue culture flasks on a rocker mimics a wave-type bag bioreactor that generates much lower shear of approximately 0.01 N/m 2 measured in previous studies 52 agitation on a rocker in the following step might be beneficial for the hematopoietic differentiation by enhancing transport and preventing complete attachment leading to loss of EB structures.…”

Section: Discussionmentioning

confidence: 99%

“…BC1 and TNC1 hiPSCs were expanded in 100-ml spinner flasks (CELLSPIN, Integra Biosciences) as cell aggregates in E8 medium (Essential 8, Thermo Fisher Scientific) as previously described 36 to yield a large quantity. Cell aggregates were dissociated into single cells by Accutase and inoculated at 4 × 10 5 cells/ml in spinner flasks at agitating speed of [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] rpm to initiate EB formation in 40 ml E8-based EB-formation medium (E8-EB medium), which is E8 medium supplemented with 10 ng/ml BMP4 (R&D Systems), 0.5% w/v human albumin (Plasbumin-25, Amgen), and 10 µM ROCK inhibitor Y27632 (Stemgent). This was marked as day 0 of differentiation.…”

Section: Eb Differentiation Using Sf-ts-tr Methodsmentioning

confidence: 99%

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Scalable Production of Human Erythrocytes from Induced Pluripotent Stem Cells

Wang

Gao

et al. 2016

Preprint

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In vitro production of erythrocytes in physiologic numbers from human induced pluripotent stem cells (hiPSCs) holds great promise for improved transfusion medicine and novel cell therapies. We report here, for the first time, a strategy for scalable and xeno-free differentiation of hematopoietic stem/progenitor cells from hiPSCs and subsequent erythrocytes specification, by using stepwise cell culture conditions and by integrating spinner flasks and rocker. This system supported robust and reproducible definitive hematopoietic differentiation of multiple hiPSC lines. We demonstrated an ultra-high yield of up to 4×10 9 CD235a + erythrocytes at >98% purity when using a 1-litre spinner flask for suspension culture. Erythrocytes generated from our system can reach a mature stage with red blood cell (RBC) characteristics of enucleation, βglobin protein expression and oxygen-binding ability. The entire process is xeno-free and clinically compliant, allowing future mass production of hiPSC-derived RBCs for transfusion medicine purposes.

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Section: Discussionmentioning

confidence: 99%

Section: Eb Differentiation Using Sf-ts-tr Methodsmentioning

confidence: 99%

Scalable Production of Human Erythrocytes from Induced Pluripotent Stem Cells

Wang

Gao

et al. 2016

Preprint

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“…HPSCs are sensitive to biomechanical cues of the microenvironment [63][64][65] and respond quickly to stiffness change [65,66] . For hPSCs, a stiff surface was found to promote cell attachment and proliferation with dense F-actin expression while a soft surface led to cell detachment [67] .…”

Section: Effects Of Ecm On Npc Differentiation From Pscsmentioning

confidence: 99%

Neural differentiation from pluripotent stem cells: The role of natural and synthetic extracellular matrix

Liu

Yan

et al. 2014

WJSC

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Neural cells differentiated from pluripotent stem cells (PSCs), including both embryonic stem cells and induced pluripotent stem cells, provide a powerful tool for drug screening, disease modeling and regenerative medicine. High-purity oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) have been derived from PSCs recently due to the advancements in understanding the developmental signaling pathways. Extracellular matrices (ECM) have been shown to play important roles in regulating the survival, proliferation, and differentiation of neural cells. To improve the function and maturation of the derived neural cells from PSCs, understanding the effects of ECM over the course of neural differentiation of PSCs is critical. During neural differentiation of PSCs, the cells are sensitive to the properties of natural or synthetic ECMs, including biochemical composition, biomechanical properties, and structural/topographical features. This review summarizes recent advances in neural differentiation of human PSCs into OPCs and NPCs, focusing on the role of ECM in modulating the composition and function of the differentiated cells. Especially, the importance of using three-dimensional ECM scaffolds to simulate the in vivo microenvironment for neural differentiation of PSCs is highlighted. Future perspectives including the immediate applications of PSC-derived neural cells in drug screening and disease modeling are also discussed.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Pluripotent stem cells; Neural differentiation; Extracellular matrix; Three-dimensional; Drug screening Core tip: Neural cells derived from human pluripotent stem cells (hPSCs), including oligodendrocyte progenitor cells and neural progenitor cells, emerge as an unlimited and physiologically relevant cell source for drug screening, disease modeling, and regenerative medicine. Natural and synthetic extracellular matrices play an important role in regulating neural differentiation, cell migration, and the derived neural cell maturation. Recent advances in neural differentiation of hPSCs on extracellular matrices in 2-D and 3-D systems are reviewed in this paper. The immediate applications of the derived neural cells in drug screening and disease modeling are also discussed.

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“…Stem cells are mechanosensitive and respond to the deformation characteristics in all axes of the scaffolds (Fozdar, Soman, Lee, Han, & Chen, ; Soman, Lee, Phadke, Varghese, & Chen, ). Pluripotent stem cells (PSCs) are sensitive to biophysical cues of the microenvironment (Earls, Jin, & Ye, ; Gonzalez‐Rodriguez, Guevorkian, Douezan, & Brochard‐Wyart, ; Song, Wang, Li, & Yang, ; Sun et al, ) and respond quickly to the stiffness change (Eroshenko, Ramachandran, Yadavalli, & Rao, ; Sun et al, ). For example, cardiomyocytes derived from PSCs showed stiffness‐dependent contraction with higher modulus (4.4–76 kPa) leading to higher contraction stress (Hazeltine et al, ; Hazeltine et al, ; Shkumatov, Baek, & Kong, ).…”

Section: Introductionmentioning

confidence: 99%

Vascular differentiation from pluripotent stem cells in 3‐D auxetic scaffolds

Song

Ahmed

et al. 2018

J Tissue Eng Regen Med

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Auxetic scaffolds, that is, scaffolds that can display negative Poisson's ratio, have unique physical properties and can expand transversally when axially strained or contract under compression. Auxetic materials have been used for bioprostheses and artery stents due to the enhanced compressive strength and shear stiffness. In vascular tissue engineering, auxetic scaffolds allow the widening of blood vessels when blood flows through (creating compressive stress) to prevent the blockage. However, the influence of auxetic materials on the cellular fate decision in local environment is unclear. In this study, auxetic polyurethane foams were used to support vascular differentiation from pluripotent stem cells. The expression of alkaline phosphatase, Oct-4, and Nanog was lower after 4 days of differentiation for the cells grown in auxetic scaffolds. Higher expression of vascular markers CD31 and VE-cadherin was observed for the cells from auxetic scaffolds compared with those from the scaffolds before auxetic conversion. Little influence on the expression of cardiac marker α-actinin was observed. The vascular cells secreted extracellular matrix proteins vitronectin and laminin and expressed membrane-bound matrix metalloproteinase 9. The examination of Yes-associated protein expression indicated more cytoplasmic retention in the cells from auxetic scaffolds compared with those from regular scaffolds, suggesting that the auxetic scaffolds may affect cellular contraction. This study demonstrates a novel 3-D culture based on auxetic scaffolds for vascular differentiation and provides a platform to study the influence of biophysical microenvironments on differentiation of pluripotent stem cells. The outcome of this study has implications for regenerative medicine and drug discovery.

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Mechanobiology of Human Pluripotent Stem Cells

Cited by 26 publications

References 88 publications

Scalable Production of Human Erythrocytes from Induced Pluripotent Stem Cells

Scalable Production of Human Erythrocytes from Induced Pluripotent Stem Cells

Neural differentiation from pluripotent stem cells: The role of natural and synthetic extracellular matrix

Vascular differentiation from pluripotent stem cells in 3‐D auxetic scaffolds

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