Continuous-flow sorting of stem cells and differentiation products based on dielectrophoresis

Song, Hongjun; Rosano, Jenna M.; Wang, Yi; Garson, Charles J.; Prabhakarpandian, Balabhaskar; Pant, Kapil; Klarmann, George J.; Perantoni, Alan O.; Alvarez, Luis M.; Lai, Eva

doi:10.1039/c4lc01253d

Cited by 159 publications

(127 citation statements)

References 46 publications

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“…Recently, Li et al (2014) developed a cell sorting chip for processing whole blood, combining TFF with a microfiltration membrane, that could recover 27% of white blood cells with 94% purity. Using a dielectrophoresis-based device for separation of stem cells and their differentiation progeny (osteoblasts), Song et al (2015) achieved a collection efficiency of up to 92% and 67% for stem cells and osteoblasts, with a purity of up to 84% and 87%, respectively. Reported separation devices for human cell separation, however, focus on lowthroughput applications, typically performing in the ll/min (Ji et al, 2008;Sethu et al, 2006;and Song et al, 2015) to ml/h range (Li et al, 2014 andZhang et al, 2012) and depending on the underlying methodology, may encounter scaling difficulties.…”

Section: Discussionmentioning

confidence: 99%

A scalable label-free approach to separate human pluripotent cells from differentiated derivatives

et al. 2016

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The broad capacity of pluripotent human embryonic stem cells (hESC) to grow and differentiate demands the development of rapid, scalable, and label-free methods to separate living cell populations for clinical and industrial applications. Here, we identify differences in cell stiffness, expressed as cell elastic modulus (CEM), for hESC versus mesenchymal progenitors, osteoblast-like derivatives, and fibroblasts using atomic force microscopy and data processing algorithms to characterize the stiffness of cell populations. Undifferentiated hESC exhibited a range of CEMs whose median was nearly three-fold lower than those of differentiated cells, information we exploited to develop a label-free separation device based on the principles of tangential flow filtration. To test the device's utility, we segregated hESC mixed with fibroblasts and hESC-mesenchymal progenitors induced to undergo osteogenic differentiation. The device permitted a throughput of 10 6 -10 7 cells per min and up to 50% removal of specific cell types per single pass. The level of enrichment and depletion of soft, pluripotent hESC in the respective channels was found to rise with increasing stiffness of the differentiating cells, suggesting CEM can serve as a major discriminator. Our results demonstrate the principle of a scalable, label-free, solution for separation of heterogeneous cell populations deriving from human pluripotent stem cells. V C 2016 AIP Publishing LLC.

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Section: Discussionmentioning

confidence: 99%

A scalable label-free approach to separate human pluripotent cells from differentiated derivatives

et al. 2016

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“…Two publications demonstrate sorting of human BMSCs (Song et al, 2015;Vykoukal et al, 2008). In the first, a human immortalised MSC cell line was differentiated into osteoblasts.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Skeletal stem cell isolation: A review on the state-of-the-art microfluidic label-free sorting techniques

Martín

Oreffo

Morgan

2016

Biotechnology Advances

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Skeletal stem cells (SSC) are a sub-population of bone marrow stromal cells that reside in postnatal bone marrow with osteogenic, chondrogenic and adipogenic differentiation potential. SSCs reside only in the bone marrow and have organisational and regulatory functions in the bone marrow microenvironment and give rise to the haematopoiesis-supportive stroma. Their differentiation capacity is restricted to skeletal lineages and therefore the term SSC should be clearly distinguished from mesenchymal stem cells which are reported to exist in extra-skeletal tissues and, critically, do not contribute to skeletal development.SSCs are responsible for the unique regeneration capacity of bone and offer unlimited potential for application in bone regenerative therapies. A current unmet challenge is the isolation of homogeneous populations of SSCs, in vitro, with homogeneous regeneration and differentiation capacities. Challenges that limit SSC isolation include a) the scarcity of SSCs in bone marrow aspirates, estimated at between 1 in 10-100,000 mononuclear cells; b) the absence of specific markers and thus the phenotypic ambiguity of the SSC and c) the complexity of bone marrow tissue.Microfluidics provides innovative approaches for cell separation based on bio-physical features of single cells. Here we review the physical principles underlying label-free microfluidic sorting techniques and review their capacity for stem cell selection/sorting from complex (heterogeneous) samples.

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“…5(a)). 73 The principle of the device is based on the accumulation of multiple DEP forces to deflect cells laterally in conjunction with the alternating on/off electric field to manipulate the cell. Collection efficiencies up to 92% and 67% for stem cells and osteoblasts along with purity up to 84% and 87%, respectively, were achieved.…”

Section: Dielectrophoresismentioning

confidence: 99%

Microfluidics cell sample preparation for analysis: Advances in efficient cell enrichment and precise single cell capture

et al. 2017

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Single cell analysis has received increasing attention recently in both academia and clinics, and there is an urgent need for effective upstream cell sample preparation. Two extremely challenging tasks in cell sample preparation-highefficiency cell enrichment and precise single cell capture-have now entered into an era full of exciting technological advances, which are mostly enabled by microfluidics. In this review, we summarize the category of technologies that provide new solutions and creative insights into the two tasks of cell manipulation, with a focus on the latest development in the recent five years by highlighting the representative works. By doing so, we aim both to outline the framework and to showcase example applications of each task. In most cases for cell enrichment, we take circulating tumor cells (CTCs) as the target cells because of their research and clinical importance in cancer. For single cell capture, we review related technologies for many kinds of target cells because the technologies are supposed to be more universal to all cells rather than CTCs. Most of the mentioned technologies can be used for both cell enrichment and precise single cell capture. Each technology has its own advantages and specific challenges, which provide opportunities for researchers in their own area. Overall, these technologies have shown great promise and now evolve into real clinical applications. Published by AIP Publishing. [http://dx

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Continuous-flow sorting of stem cells and differentiation products based on dielectrophoresis

Cited by 159 publications

References 46 publications

A scalable label-free approach to separate human pluripotent cells from differentiated derivatives

A scalable label-free approach to separate human pluripotent cells from differentiated derivatives

Skeletal stem cell isolation: A review on the state-of-the-art microfluidic label-free sorting techniques

Microfluidics cell sample preparation for analysis: Advances in efficient cell enrichment and precise single cell capture

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