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Expansion of functional personalized cells with specific transgene combinations.

ABSTRACT: Fundamental research and drug development for personalized medicine necessitates cell cultures from defined genetic backgrounds. However, providing sufficient numbers of authentic cells from individuals poses a challenge. Here, we present a new strategy for rapid cell expansion that overcomes current limitations. Using a small gene library, we expanded primary cells from different tissues, donors, and species. Cell-type-specific regimens that allow the reproducible creation of cell lines were identified. In depth characterization of a series of endothelial and hepatocytic cell lines confirmed phenotypic stability and functionality. Applying this technology enables rapid, efficient, and reliable production of unlimited numbers of personalized cells. As such, these cell systems support mechanistic studies, epidemiological research, and tailored drug development.

SUBMITTER: Lipps C

PROVIDER: S-EPMC5843645 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Expansion of functional personalized cells with specific transgene combinations.

Lipps Christoph C Klein Franziska F Wahlicht Tom T Seiffert Virginia V Butueva Milada M Zauers Jeannette J Truschel Theresa T Luckner Martin M Köster Mario M MacLeod Roderick R Pezoldt Jörn J Hühn Jochen J Yuan Qinggong Q Müller Peter Paul PP Kempf Henning H Zweigerdt Robert R Dittrich-Breiholz Oliver O Pufe Thomas T Beckmann Rainer R Drescher Wolf W Riancho Jose J Sañudo Carolina C Korff Thomas T Opalka Bertram B Rebmann Vera V Göthert Joachim R JR Alves Paula M PM Ott Michael M Schucht Roland R Hauser Hansjörg H Wirth Dagmar D May Tobias T

Nature communications 20180308 1

Fundamental research and drug development for personalized medicine necessitates cell cultures from defined genetic backgrounds. However, providing sufficient numbers of authentic cells from individuals poses a challenge. Here, we present a new strategy for rapid cell expansion that overcomes current limitations. Using a small gene library, we expanded primary cells from different tissues, donors, and species. Cell-type-specific regimens that allow the reproducible creation of cell lines were id ...[more]

PMID: 29520052

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Project description:PurposeFunctional-guided radiation therapy (RT) plans have the potential to limit damage to normal tissue and reduce toxicity. Although functional imaging modalities have continued to improve, a limited understanding of the functional response to radiation and its application to personalized therapy has hindered clinical implementation. The purpose of this study was to retrospectively model the longitudinal, patient-specific dose-function response in non-small cell lung cancer patients treated with RT to better characterize the expected functional damage in future, unknown patients.Methods and materialsPerfusion single-photon emission computed tomography/computed tomography scans were obtained at baseline (n = 81), midtreatment (n = 74), 3 months post-treatment (n = 51), and 1 year post-treatment (n = 26) and retrospectively analyzed. Patients were treated with conventionally fractionated RT or stereotactic body RT. Normalized perfusion single-photon emission computed tomography voxel intensity was used as a surrogate for local lung function. A patient-specific logistic model was applied to each individual patient's dose-function response to characterize functional reduction at each imaging time point. Patient-specific model parameters were averaged to create a population-level logistic dose-response model.ResultsA significant longitudinal decrease in lung function was observed after RT by analyzing the voxelwise change in normalized perfusion intensity. Generated dose-function response models represent the expected voxelwise reduction in function, and the associated uncertainty, for an unknown patient receiving conventionally fractionated RT or stereotactic body RT. Differential treatment responses based on the functional status of the voxel at baseline suggest that initially higher functioning voxels are damaged at a higher rate than lower functioning voxels.ConclusionsThis study modeled the patient-specific dose-function response in patients with non-small cell lung cancer during and after radiation treatment. The generated population-level dose-function response models were derived from individual patient assessment and have the potential to inform functional-guided treatment plans regarding the expected functional lung damage. This type of patient-specific modeling approach can be applied broadly to other functional response analyses to better capture intrapatient dependencies and characterize personalized functional damage.

Dataset Information

Expansion of functional personalized cells with specific transgene combinations.

Publications

Expansion of functional personalized cells with specific transgene combinations.

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