Finding the winning combination

Memić, Adnan; Khademhosseini, Ali

doi:10.4161/org.29646

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…Our results demonstrate that 3-D Haralick texture features can also be employed to deduce organizational variations for nuclear reporters in stem cells in-response to external stimuli, and for profiling long-term cell-fate determinations in 3-D microenvironments. This approach opens new avenues to facilitate the screening of dynamic and combinatorial 3-D platforms being developed [51–53] to guide optimal stem cell fate decisions. It allows characterization and modeling of the early cell response as well as high throughput screening, and thereby has the potential to significantly reduce the time and developmental cost for next generation biomaterials.…”

Section: Discussionmentioning

confidence: 99%

Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics

et al. 2016

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A predictive framework for the evolution of stem cell biology in 3-D is currently lacking. In this study we propose deep image informatics of the nuclear biology of stem cells to elucidate how 3-D biomaterials steer stem cell lineage phenotypes. The approach is based on high content imaging informatics to capture minute variations in the 3-D spatial organization of splicing factor SC-35 in the nucleoplasm as a marker to classify emergent cell phenotypes of human mesenchymal stem cells (hMSCs). The cells were cultured in varied 3-D culture systems including hydrogels, electrospun mats and salt leached scaffolds. The approach encompasses high resolution 3-D imaging of SC-35 domains and high content image analysis (HCIA) to compute quantitative 3-D nuclear metrics for SC-35 organization in single cells in concert with machine learning approaches to construct a predictive cell-state classification model. Our findings indicate that hMSCs cultured in collagen hydrogels and induced to differentiate into osteogenic or adipogenic lineages could be classified into the three lineages (stem, adipogenic, osteogenic) with ≥ 80% precision and sensitivity, within 72 hours. Using this framework, the augmentation of osteogenesis by scaffold design exerted by porogen leached scaffolds was also profiled within 72 hours with ~80% high sensitivity. Furthermore, by employing 3-D SC-35 organizational metrics, differential osteogenesis induced by novel electrospun fibrous polymer mats incorporating decellularized matrix could also be elucidated and predictably modeled at just 3 days with high precision. We demonstrate that 3-D SC-35 organizational metrics can be applied to model the stem cell state in 3-D scaffolds. We propose that this methodology can robustly discern minute changes in stem cell states within complex 3-D architectures and map single cell biological readouts that are critical to assessing population level cell heterogeneity.

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Section: Discussionmentioning

confidence: 99%

Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics

et al. 2016

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“…Another class of emerging high-throughput screening studies are based on culturing and evaluating cells in 3D microevironments, mimicking the physiological dimensionality (Floren, Tan 2015; Memic, Khademhosseini 2014). Floren M et.…”

Section: High Throughput Platforms To Screen Complex Cell-nichesmentioning

confidence: 99%

“…al. (2014) by utilizing a robotic microarray spotter to rapidly print droplets consisting of MSCs, gelatin methacrylate, prepolymer solution and various ECM proteins on TMSPMA functionalized glass slide, and applied to identify optimal niche for osteogenesis (Memic, Khademhosseini 2014). Such platforms are especially useful in designing scaffolds for 3-D and in-vivo applications.…”

Section: High Throughput Platforms To Screen Complex Cell-nichesmentioning

confidence: 99%

Convergence of Highly Resolved and Rapid Screening Platforms with Dynamically Engineered, Cell Phenotype-Prescriptive Biomaterials

2016

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Biophysical and biochemical cues from the cellular microenvironment initiate intracellular signaling through cellular membrane receptors and trigger specific cell developmental programs. Extracellular substrates and matrix scaffolds engineered to mimic cell’s native physiological environment must incorporate the multifactorial parameters (composition, micro and nanoscale organization and topography) of the extracellular matrix as well as the dynamic nature of the matrix. The design of such engineered biomaterials is challenged by the inherent complexity and dynamic nature of the cell-extracellular matrix reciprocity, while the validation of robust microenvironments requires a deeper, higher content phenotypic resolution of cell-matrix interactions alongside a rapid screening capability. To this end, high-throughput platforms are integral to facilitating the screening and optimization of complex engineered microenvironments for directing desired cell developmental pathway. This review highlights the recent advances in biomaterial platforms that present dynamic cues and enable high throughput screening of cell’s response to a combination of micro-environmental factors. We also address some newer techniques involving high content image informatics to elucidate emergent cellular behaviors with a focus on stem cell regenerative endpoints.

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Design Considerations When Creating a High Throughput Screen-Compatible In Vitro Model of Osteogenesis

Doyle,

Cazzola,

Coleman

2024

SLAS Discovery

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Finding the winning combination

Cited by 5 publications

References 30 publications

Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics

Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics

Convergence of Highly Resolved and Rapid Screening Platforms with Dynamically Engineered, Cell Phenotype-Prescriptive Biomaterials

Design Considerations When Creating a High Throughput Screen-Compatible In Vitro Model of Osteogenesis

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