1 Separation of Tumor Cells from Fibroblasts.- 2 Development of Media for Isolation and Cultivation of Human Cancer Cells.- 3 New Approaches to the Cultivation of Human Breast Carcinomas.- 4 Old and New Problems in Human Tumor Cell Cultivation.- 5 New Human Tumor Cell Lines.- 6 Human Brain Tumor Cells in Matrix Culture.- 7 Neoplastic Human Glia Cells in Culture.- 8 Current Research with Organ Cultures of Human Tumors.- 9 Metabolic Gradients in Tissue Culture Studies of Human Cancer Cells.- 10 Human Lung Cancer in Tissue Culture.- 11 Cell Lines from Humans with Hematopoietic Malignancies.- 12 Cytological Characterization of Human Tumor Cells from Monolayer Cultures.- 13 Chromosome Abnormalities in Human Tumor Cells in Culture.- 14 Ultrastructural Characteristics of Human Tumor Cells in Vitro.- 15 The Strategy of a Search for Viral Involvement in Human Cancer.- 16 Helper Activity for the Defective Friend Leukemia Virus in Human Malignant Cell Cultures.

Human tumor cells in vitro

Pluripotent stem cells can be generated from the somatic cells of humans and are a useful model to study disease. Here, pluripotent stem cells are made from a patient with familial Parkinson's disease, and the resulting neurons exhibit elevated levels of α-synuclein, recapitulating the molecular features of the patient's disease.

/pdf/parkinson-s-disease-induced-pluripotent-stem-cells-with-fzf5gjy7j1.pdf

Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus

Perspectives on alkaline phosphatase isoenzymes

Reproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14 stock HeLa samples from 13 international laboratories. We cultured cells in uniform conditions and profiled genome-wide copy numbers, mRNAs, proteins and protein turnover rates in each cell line. We discovered substantial heterogeneity between HeLa variants, especially between lines of the CCL2 and Kyoto varieties, and observed progressive divergence within a specific cell line over 50 successive passages. Genomic variability has a complex, nonlinear effect on transcriptome, proteome and protein turnover profiles, and proteotype patterns explain the varying phenotypic response of different cell lines to Salmonella infection. These findings have implications for the interpretation and reproducibility of research results obtained from human cultured cells.

/pdf/multi-omic-measurements-of-heterogeneity-in-hela-cells-1cx6yjstlv.pdf

Multi-omic measurements of heterogeneity in HeLa cells across laboratories

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.

/pdf/creation-of-an-open-access-mutation-defined-fibroblast-ptram5d4ps.pdf

Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research

Seven strains of HeLa cells have been characterized by the number of chromosomes and the activity of the enzymes alkaline phosphatase, glucose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase, and lactic dehydrogenase. All seven strains were found to differ as to chromosome numbers and enzyme levels despite the fact that two strains were called HeLa and three were called HeLa S3. Three strains were found to have a stemline in which greater than 60% of the cells demonstrated a single chromosome number, and this characteristic was stable for at least 6 months. A nomenclature for these clones has been suggested by the use of the stemline chromosome number as a subscript following HeLa. These three clones were, therefore, designated HeLa65, HeLa71, and HeLa75. Karyotypes were made of the stemlines of these clones and were compared with enzyme levels. Alkaline phosphatase showed the greatest variation from cell line to cell line with a 200-fold difference in levels, whereas glucose-6-phosphate dehydrogenase showed variation in activity over a 12-fold range, lactic dehydrogenase over an 8-fold range, and 6-phosphogluconic dehydrogenase over a 2-fold range. It is suggested that human cell strains can be used for biochemical studies if they are cloned and if the clones are relatively stable at least with respect to modal chromosome number and karyotype.

https://rupress.org/jcb/article-pdf/41/3/806/1069099/806.pdf

R. H. Bottomley

Papers

Enzymatic and chromosomal characterization of HeLa variants.