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Article ; Online: Cell-based therapy approaches: the hope for incurable diseases.

Buzhor, Ella / Leshansky, Lucy / Blumenthal, Jacob / Barash, Hila / Warshawsky, David / Mazor, Yaron / Shtrichman, Ronit

Regenerative medicine

2014 Volume 9, Issue 5, Page(s) 649–672

Abstract: Cell therapies aim to repair the mechanisms underlying disease initiation and progression, achieved through trophic effect or by cell replacement. Multiple cell types can be utilized in such therapies, including stem, progenitor or primary cells. This ... ...

Abstract	Cell therapies aim to repair the mechanisms underlying disease initiation and progression, achieved through trophic effect or by cell replacement. Multiple cell types can be utilized in such therapies, including stem, progenitor or primary cells. This review covers the current state of cell therapies designed for the prominent disorders, including cardiovascular, neurological (Parkinson's disease, amyotrophic lateral sclerosis, stroke, spinal cord injury), autoimmune (Type 1 diabetes, multiple sclerosis, Crohn's disease), ophthalmologic, renal, liver and skeletal (osteoarthritis) diseases. Various cell therapies have reached advanced clinical trial phases with potential marketing approvals in the near future, many of which are based on mesenchymal stem cells. Advances in pluripotent stem cell research hold great promise for regenerative medicine. The information presented in this review is based on the analysis of the cell therapy collection detailed in LifeMap Discovery(®) (LifeMap Sciences Inc., USA) the database of embryonic development, stem cell research and regenerative medicine.
MeSH term(s)	Autoimmune Diseases/therapy ; Cell- and Tissue-Based Therapy/trends ; Humans ; Kidney Diseases/therapy ; Liver Diseases/therapy ; Nervous System Diseases/therapy ; Osteoarthritis/therapy ; Regenerative Medicine/trends ; Spinal Cord Injuries/therapy ; Stem Cell Transplantation ; Vascular Diseases/therapy
Language	English
Publishing date	2014
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274500-2
ISSN	1746-076X ; 1746-0751
ISSN (online)	1746-076X
ISSN	1746-0751
DOI	10.2217/rme.14.35
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Article ; Online: Chromatin-modifying agents reactivate embryonic renal stem/progenitor genes in human adult kidney epithelial cells but abrogate dedifferentiation and stemness.

Omer, Dorit / Harari-Steinberg, Orit / Buzhor, Ella / Metsuyanim, Sally / Pleniceanu, Oren / Zundelevich, Adi / Gal-Yam, Einav Nili / Dekel, Benjamin

Cellular reprogramming

2013 Volume 15, Issue 4, Page(s) 281–292

Abstract: Recent studies have suggested that epigenetic modulation with chromatin-modifying agents can induce stemness and dedifferentiation and increase developmental plasticity. For instance, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has been ... ...

Abstract	Recent studies have suggested that epigenetic modulation with chromatin-modifying agents can induce stemness and dedifferentiation and increase developmental plasticity. For instance, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has been shown to promote self-renewal/expansion of hematopoietic stem cells and facilitate the generation of induced pluripotent stem cells (iPSCs). Previously, we observed that downregulation of embryonic renal stem/progenitor genes in the adult kidney was associated, at least in part, with epigenetic silencing. Therefore, we hypothesized that VPA may alter the expression of these genes and reprogram mature human adult kidney epithelial cells (hKEpCs) to a stem/progenitor-like state. Here, using quantitative RT-PCR and flow cytometry [fluorescence-activated cell sorting (FACS)] analysis, we show in VPA-treated primary cultures of human adult and fetal kidney significant reinduction of the renal stem/progenitor markers SIX2, OSR1, SALL1, NCAM, and PSA-NCAM. Robust SIX2 mRNA re-expression was confirmed at the protein level by western blot and was associated with epigenetic changes of the histones at multiple sites of the SIX2 promoter leading to gene activation, significantly increased acetylation of histones H4, and methylation of lysine 4 on H3. Furthermore, we could demonstrate synergistic effects of VPA and Wnt antagonists on SIX2 and also OSR1 reinduction. Nevertheless, VPA resulted in upregulation of E-CADHERIN and reduction in VIMENTIN, preventing the skewing of hKEpCs towards a more replicative mesenchymal state required for clonogenic expansion and acquisition of stem cell characters, altogether inducing cell senescence at early passages. These results demonstrating that chromatin-modifying agents prevent dedifferentiation of hKEpCs have important clinical implications as they may limit ex-vivo self-renewal/expansion and possibly the in vivo renal regenerative capacity initiated by dedifferentiation.
MeSH term(s)	Adult ; Animals ; Cell Dedifferentiation/drug effects ; Cell Dedifferentiation/genetics ; Cell Differentiation/drug effects ; Cell Differentiation/genetics ; Cells, Cultured ; Chick Embryo ; Chromatin Assembly and Disassembly/drug effects ; Embryonic Stem Cells/drug effects ; Embryonic Stem Cells/physiology ; Epithelial Cells/drug effects ; Epithelial Cells/physiology ; Fetus/cytology ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Kidney/cytology ; Kidney/embryology ; Valproic Acid/pharmacology
Chemical Substances	Histone Deacetylase Inhibitors ; Valproic Acid (614OI1Z5WI)
Language	English
Publishing date	2013-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2542436-1
ISSN	2152-4998 ; 1557-7457 ; 2152-4971
ISSN (online)	2152-4998 ; 1557-7457
ISSN	2152-4971
DOI	10.1089/cell.2012.0087
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Article ; Online: Pancreatic cancer ascites xenograft-an expeditious model mirroring advanced therapeutic resistant disease.

Golan, Talia / Stossel, Chani / Schvimer, Michael / Atias, Dikla / Halperin, Sharon / Buzhor, Ella / Raitses-Gurevich, Maria / Cohen, Keren / Pri-Chen, Sara / Wilson, Julie / Denroche, Robert E / Lungu, Ilinca / Bartlett, John M S / Mbabaali, Faridah / Yarden, Yosef / Nataraj, Nishanth Belugali / Gallinger, Steven / Berger, Raanan

Oncotarget

2017 Volume 8, Issue 25, Page(s) 40778–40790

Abstract: Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up ...

Abstract	Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20-30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource of metastatic peritoneal spread. In this study, we utilized pancreatic ascites/pleural effusion cancer cells to establish patient derived xenografts.Ascites/pleural effusion-patient derived xenografts were established from twelve independent cases. Xenografts were serially passed in nude mice and tissue bio-specimen banking has been established. Histopathology of emergent tumors demonstrates poorly to moderately differentiated, glandular and mucin producing tumors, mirroring morphology of primary pancreatic cancer tumors. Whole genome sequencing of six patient derived xenografts samples demonstrates common mutations and structural variations similar to those reported in primary pancreatic cancer. Xenograft tumors were dissociated to single-cells and in-vitro drug sensitivity screen assays demonstrated chemo-resistance, correlating with patient clinical scenarios, thus serving as a platform for clinically relevant translational research.Therefore, establishment of this novel ascites/pleural effusion patient derived xenograft model, with extensive histopathology and genomic characterization, opens an opportunity for the study of advanced aggressive pancreatic cancer. Characterization of metastatic disease and mechanisms of resistance to therapeutics may lead to the development of novel drug combinations.
Language	English
Publishing date	2017-06-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.17253
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Article ; Online: A rapid in vivo assay system for analyzing the organogenetic capacity of human kidney cells.

Noiman, Tsahi / Buzhor, Ella / Metsuyanim, Sally / Harari-Steinberg, Orit / Morgenshtern, Chaya / Dekel, Benjamin / Goldstein, Ronald S

Organogenesis

2011 Volume 7, Issue 2, Page(s) 140–144

Abstract: Transplantation of human kidney-derived cells is a potential therapeutic modality for promoting regeneration of diseased renal tissue. However, assays that determine the ability of candidate populations for renal cell therapy to undergo appropriate ... ...

Abstract	Transplantation of human kidney-derived cells is a potential therapeutic modality for promoting regeneration of diseased renal tissue. However, assays that determine the ability of candidate populations for renal cell therapy to undergo appropriate differentiation and morphogenesis are limited. We report here a rapid and humane assay for characterizing tubulogenic potency utilizing the well-established chorioallantoic membrane CAM) of the chick embryo. Adult human kidney-derived cells expanded in monolayer were suspended in Matrigel and grafted onto the CAM. After a week, grafts were assessed histologically. Strikingly, many of the renal cells self-organized into tubular structures. Host blood vessels penetrated and presumably fed the grafts. Immuno- and histochemical staining revealed that tubular structures were epithelial, but not blood vessels. Some of the cells both within and outside the tubules were dividing. Analysis for markers of proximal and distal renal tubules revealed that grafts contained individual cells of a proximal tubular phenotype and many tubules of distal tubule character. Our results demonstrate that the chick CAM is a useful xenograft system for screening for differentiation and morphogenesis in cells with potential use in renal regenerative medicine.
MeSH term(s)	Adult ; Animals ; Biological Assay/methods ; Chickens ; Chorioallantoic Membrane/metabolism ; HEK293 Cells ; Humans ; Immunohistochemistry ; Kidney/cytology ; Organogenesis ; Stem Cell Transplantation ; Stem Cells/cytology
Language	English
Publishing date	2011-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2159583-5
ISSN	1555-8592 ; 1555-8592
ISSN (online)	1555-8592
ISSN	1555-8592
DOI	10.4161/org.7.2.16457
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Article ; Online: Harnessing synthetic lethality to predict the response to cancer treatment.

Lee, Joo Sang / Das, Avinash / Jerby-Arnon, Livnat / Arafeh, Rand / Auslander, Noam / Davidson, Matthew / McGarry, Lynn / James, Daniel / Amzallag, Arnaud / Park, Seung Gu / Cheng, Kuoyuan / Robinson, Welles / Atias, Dikla / Stossel, Chani / Buzhor, Ella / Stein, Gidi / Waterfall, Joshua J / Meltzer, Paul S / Golan, Talia /

Hannenhalli, Sridhar / Gottlieb, Eyal / Benes, Cyril H / Samuels, Yardena / Shanks, Emma / Ruppin, Eytan

Nature communications

2018 Volume 9, Issue 1, Page(s) 2546

Abstract: While synthetic lethality (SL) holds promise in developing effective cancer therapies, SL candidates found via experimental screens often have limited translational value. Here we present a data-driven approach, ISLE (identification of clinically ... ...

Abstract	While synthetic lethality (SL) holds promise in developing effective cancer therapies, SL candidates found via experimental screens often have limited translational value. Here we present a data-driven approach, ISLE (identification of clinically relevant synthetic lethality), that mines TCGA cohort to identify the most likely clinically relevant SL interactions (cSLi) from a given candidate set of lab-screened SLi. We first validate ISLE via a benchmark of large-scale drug response screens and by predicting drug efficacy in mouse xenograft models. We then experimentally test a select set of predicted cSLi via new screening experiments, validating their predicted context-specific sensitivity in hypoxic vs normoxic conditions and demonstrating cSLi's utility in predicting synergistic drug combinations. We show that cSLi can successfully predict patients' drug treatment response and provide patient stratification signatures. ISLE thus complements existing actionable mutation-based methods for precision cancer therapy, offering an opportunity to expand its scope to the whole genome.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Biomarkers, Pharmacological ; Cell Hypoxia ; Cell Line, Tumor ; Drug Combinations ; Drug Synergism ; High-Throughput Screening Assays ; Humans ; Mice ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/mortality ; Patient Selection ; Precision Medicine/methods ; Precision Medicine/statistics & numerical data ; Synthetic Lethal Mutations/drug effects ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Biomarkers, Pharmacological ; Drug Combinations
Language	English
Publishing date	2018-06-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-018-04647-1
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Article ; Online: Recapitulating the clinical scenario of BRCA-associated pancreatic cancer in pre-clinical models.

International journal of cancer

2018 Volume 143, Issue 1, Page(s) 179–183

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. BRCA-associated PDAC comprises a clinically relevant subtype. A portion of these patients are highly susceptible to DNA damaging therapeutics, however, responses are ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. BRCA-associated PDAC comprises a clinically relevant subtype. A portion of these patients are highly susceptible to DNA damaging therapeutics, however, responses are heterogeneous and clinical resistance evolves. We have developed unique patient-derived xenograft (PDX) models from metastatic lesions of germline BRCA-mutated patients obtained at distinct time points; before treatment and at progression. Thus, closely mimicking clinical scenarios, to further investigate treatment naïve and resistant patients. DNA was isolated from six BRCA-mutated PDXs and classified by whole-genome sequencing to stable-genome or homologous recombination deficient (HRD)-genome. The sensitivity to DNA-damaging agents was evaluated in vivo in three BRCA-associated PDAC PDXs models: (1) HRD-genome naïve to treatments; (2) stable-genome naïve to treatment; (3) HRD-genome resistant to treatment. Correlation between disease course at tissue acquisition and response to PARP inhibitor (PARPi)/platinum was demonstrated in PDXs in vivo. Only the HRD-genome PDX, naïve to treatment, was sensitive to PARP inhibitor/cisplatin treatments. Our results demonstrate heterogeneous responses to DNA damaging agents/PARPi in BRCA-associated PDX thus reflecting the wide clinical spectrum. An HRD-genome PDX generated from a naïve to treatment biopsy was sensitive to platinum/PARPi whereas no benefit was observed in treating a HRD-genome PDXs generated from a patient that had acquired resistance nor stable-genome PDXs.
MeSH term(s)	Animals ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/genetics ; Disease Progression ; Drug Resistance, Neoplasm ; Genomic Instability ; Homologous Recombination ; Humans ; Mice ; Mutation ; Neoplasm Metastasis ; Neoplasm Transplantation ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Platinum Compounds/administration & dosage ; Platinum Compounds/therapeutic use ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Prognosis ; Whole Genome Sequencing
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human ; Platinum Compounds ; Poly(ADP-ribose) Polymerase Inhibitors
Language	English
Publishing date	2018-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.31292
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Article ; Online: GeneAnalytics: An Integrative Gene Set Analysis Tool for Next Generation Sequencing, RNAseq and Microarray Data.

Ben-Ari Fuchs, Shani / Lieder, Iris / Stelzer, Gil / Mazor, Yaron / Buzhor, Ella / Kaplan, Sergey / Bogoch, Yoel / Plaschkes, Inbar / Shitrit, Alina / Rappaport, Noa / Kohn, Asher / Edgar, Ron / Shenhav, Liraz / Safran, Marilyn / Lancet, Doron / Guan-Golan, Yaron / Warshawsky, David / Shtrichman, Ronit

Omics : a journal of integrative biology

2016 Volume 20, Issue 3, Page(s) 139–151

Abstract: Postgenomics data are produced in large volumes by life sciences and clinical applications of novel omics diagnostics and therapeutics for precision medicine. To move from "data-to-knowledge-to-innovation," a crucial missing step in the current era is, ... ...

Abstract	Postgenomics data are produced in large volumes by life sciences and clinical applications of novel omics diagnostics and therapeutics for precision medicine. To move from "data-to-knowledge-to-innovation," a crucial missing step in the current era is, however, our limited understanding of biological and clinical contexts associated with data. Prominent among the emerging remedies to this challenge are the gene set enrichment tools. This study reports on GeneAnalytics™ ( geneanalytics.genecards.org ), a comprehensive and easy-to-apply gene set analysis tool for rapid contextualization of expression patterns and functional signatures embedded in the postgenomics Big Data domains, such as Next Generation Sequencing (NGS), RNAseq, and microarray experiments. GeneAnalytics' differentiating features include in-depth evidence-based scoring algorithms, an intuitive user interface and proprietary unified data. GeneAnalytics employs the LifeMap Science's GeneCards suite, including the GeneCards®--the human gene database; the MalaCards-the human diseases database; and the PathCards--the biological pathways database. Expression-based analysis in GeneAnalytics relies on the LifeMap Discovery®--the embryonic development and stem cells database, which includes manually curated expression data for normal and diseased tissues, enabling advanced matching algorithm for gene-tissue association. This assists in evaluating differentiation protocols and discovering biomarkers for tissues and cells. Results are directly linked to gene, disease, or cell "cards" in the GeneCards suite. Future developments aim to enhance the GeneAnalytics algorithm as well as visualizations, employing varied graphical display items. Such attributes make GeneAnalytics a broadly applicable postgenomics data analyses and interpretation tool for translation of data to knowledge-based innovation in various Big Data fields such as precision medicine, ecogenomics, nutrigenomics, pharmacogenomics, vaccinomics, and others yet to emerge on the postgenomics horizon.
MeSH term(s)	Algorithms ; Computational Biology/methods ; Data Mining ; Databases, Factual ; Databases, Genetic ; Gene Regulatory Networks ; Genome, Human ; High-Throughput Nucleotide Sequencing/statistics & numerical data ; Humans ; Metabolic Networks and Pathways/genetics ; Microarray Analysis/statistics & numerical data ; Software
Language	English
Publishing date	2016-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2015.0168
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Article ; Online: Reactivation of NCAM1 defines a subpopulation of human adult kidney epithelial cells with clonogenic and stem/progenitor properties.

Buzhor, Ella / Omer, Dorit / Harari-Steinberg, Orit / Dotan, Zohar / Vax, Einav / Pri-Chen, Sara / Metsuyanim, Sally / Pleniceanu, Oren / Goldstein, Ronald S / Dekel, Benjamin

The American journal of pathology

2013 Volume 183, Issue 5, Page(s) 1621–1633

Abstract: The nephron is composed of a monolayer of epithelial cells that make up its various compartments. In development, these cells begin as mesenchyme. NCAM1, abundant in the mesenchyme and early nephron lineage, ceases to express in mature kidney epithelia. ... ...

Abstract	The nephron is composed of a monolayer of epithelial cells that make up its various compartments. In development, these cells begin as mesenchyme. NCAM1, abundant in the mesenchyme and early nephron lineage, ceases to express in mature kidney epithelia. We show that, once placed in culture and released from quiescence, adult human kidney epithelial cells (hKEpCs), uniformly positive for CD24/CD133, re-express NCAM1 in a specific cell subset that attains a stem/progenitor state. Immunosorted NCAM1(+) cells overexpressed early nephron progenitor markers (PAX2, SALL1, SIX2, WT1) and acquired a mesenchymal fate, indicated by high vimentim and reduced E-cadherin levels. Gene expression and microarray analysis disclosed both a proximal tubular origin of these cells and molecules regulating epithelial-mesenchymal transition. NCAM1(+) cells generated clonal progeny when cultured in the presence of fetal kidney conditioned medium, differentiated along mesenchymal lineages but retained the unique propensity to generate epithelial kidney spheres and produce epithelial renal tissue on single-cell grafting in chick CAM and mouse. Depletion of NCAM1(+) cells from hKEpCs abrogated stemness traits in vitro. Eliminating these cells during the regenerative response that follows glycerol-induced acute tubular necrosis worsened peak renal injury in vivo. Thus, higher clone-forming and developmental capacities characterize a distinct subset of adult kidney-derived cells. The ability to influence an endogenous regenerative response via NCAM1 targeting may lead to novel therapeutics for renal diseases.
MeSH term(s)	Acute Kidney Injury/metabolism ; Acute Kidney Injury/pathology ; Adult ; Animals ; Antibodies/metabolism ; Biomarkers/metabolism ; Blood Urea Nitrogen ; CD56 Antigen/metabolism ; Cell Differentiation/genetics ; Cell Proliferation ; Chickens ; Clone Cells ; Down-Regulation/genetics ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Gene Ontology ; HEK293 Cells ; Humans ; Kidney/pathology ; Mesoderm/pathology ; Mice ; Molecular Sequence Annotation ; Nephrons/metabolism ; Nephrons/pathology ; Oligonucleotide Array Sequence Analysis ; Spheroids, Cellular/metabolism ; Spheroids, Cellular/pathology ; Stem Cells/metabolism ; Transcriptome/genetics ; Up-Regulation/genetics
Chemical Substances	Antibodies ; Biomarkers ; CD56 Antigen ; NCAM1 protein, human
Language	English
Publishing date	2013-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2013.07.034
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Article ; Online: Kidney spheroids recapitulate tubular organoids leading to enhanced tubulogenic potency of human kidney-derived cells.

Buzhor, Ella / Harari-Steinberg, Orit / Omer, Dorit / Metsuyanim, Sally / Jacob-Hirsch, Jasmine / Noiman, Tsahi / Dotan, Zohar / Goldstein, Ronald S / Dekel, Benjamin

Tissue engineering. Part A

2011 Volume 17, Issue 17-18, Page(s) 2305–2319

Abstract: Cell-based approaches utilizing autologous human renal cells require their isolation, expansion in vitro, and reintroduction back into the host for renal tissue regeneration. Nevertheless, human kidney epithelial cells (hKEpCs) lose their phenotype, ... ...

Abstract	Cell-based approaches utilizing autologous human renal cells require their isolation, expansion in vitro, and reintroduction back into the host for renal tissue regeneration. Nevertheless, human kidney epithelial cells (hKEpCs) lose their phenotype, dedifferentiate, and assume the appearance of fibroblasts after relatively few passages in culture. We hypothesized that growth conditions may influence hKEpC phenotype and function. hKEpCs retrieved from human nephrectomy tissue samples showed the ability to reproducibly form kidney spheres when grown in suspension culture developed in nonadherent conditions. Genetic labeling and time-lapse microscopy indicated, at least in part, the aggregation of hKEpCs into 3D spheroids rather than formation of pure clonally expanded spheres. Characterization of hKEpC spheroids by real-time polymerase chain reaction and FACS analysis showed upregulation of some renal developmental and "stemness" markers compared with monolayer and mostly an EpCAM(+)CD24(+)CD133(+)CD44(+) spheroid cell phenotype. Oligonucleotide microarrays, which were used to identify global transcriptional changes accompanying spheroid formation, showed predominantly upregulation of cell matrix/cell contact molecules and cellular biogenesis processes and downregulation of cell cycle, growth, and locomotion. Accordingly, hKEpC spheroids slowly proliferated as indicated by low Ki-67 staining, but when grafted in low cell numbers onto the chorioallantoic membrane (CAM) of the chick embryo, they exclusively reconstituted various renal tubular epithelia. Moreover, efficient generation of kidney spheroids was observed after long-term monolayer culture resulting in reestablishment of tubulogenic capacity upon CAM grafting. Thus, generation of a tubular organoid in hKEpC spheroids may provide a functional benefit for kidney-derived cells in vivo.
MeSH term(s)	Cell Culture Techniques ; Cells, Cultured ; Flow Cytometry ; Humans ; Kidney/cytology ; Microarray Analysis ; Organoids/cytology ; Spheroids, Cellular/cytology ; Spheroids, Cellular/metabolism
Language	English
Publishing date	2011-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2420582-5
ISSN	1937-335X ; 1937-3341
ISSN (online)	1937-335X
ISSN	1937-3341
DOI	10.1089/ten.TEA.2010.0595
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Article ; Online: Harnessing synthetic lethality to predict the response to cancer treatment

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 12

Abstract: Synthetic lethality (SL) offers a new precision oncology approach, which is based on targeting cancer-specific vulnerabilities across the whole genome, going beyond cancer drivers. The authors develop an approach termed ISLE to identify clinically ... ...

Abstract	Synthetic lethality (SL) offers a new precision oncology approach, which is based on targeting cancer-specific vulnerabilities across the whole genome, going beyond cancer drivers. The authors develop an approach termed ISLE to identify clinically relevant SL interactions and use them for patient stratification and novel target identification.
Keywords	Science ; Q
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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