Multi-stage stem cell carcinogenesis
AssigneeStemLifeLine, Inc.
InventorsAna Krtolica, Dusko Ilic
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Abstract
The present invention relates to a system of multi-stage stem cell carcinogenesis and a method of generating such multi-stage stem cell carcinogenesis system. Various stages of cancer stem cells can be generated from normal stem cells via mutagenesis. The system of the present invention enables monitoring changes in the ability of cells to transition from one stage of carcinogenesis to another and to identify genetic pathways and molecules that influence carcinogenesis. The present invention also enables a high-throughput and nonbiased screening for targets that preferentially affect cancer stem cells relative to non-cancer stem cells or their derivatives during stem cell carcinogenesis, thus is useful in developing anti-cancer therapeutics.
Claims69
A method of generating cancer stem cells (CSC) or tumor initiating cells (TIC) comprising:
- (a) contacting a non-cancer stem cell or a normal derivative thereof with at least one mutagen;
- (b) selecting stem cell clone that displays a transformed phenotype characteristic of stem cell malignant transformation.
A method of generating isogenic human CSC or TIC comprising deriving human CSC from human non-cancer stem cells or their derivatives of the same genetic origin.
A system for profiling stem cell malignant transformation (carcinogenesis) comprising
- (a) a non-cancer stem cell or its derivatives
- (b) isogenic non-cancer stem cell-derived cancer stem cells or tumor initiating cells with transformed phenotypes characteristic of each stage of stem cell malignant transformation
- (c) a database with information on molecular and/or cellular characteristics of stem cell malignant transformation
A method of profiling stem cell malignant transformation comprising
- (a) generating stage-specific cancer stem cells from isogenic non-cancer stem cells or their derivatives
- (b) identifying molecular and/or cellular characteristics associated with each stage of stem cell malignant transformation
- (c) generating a database with information on molecular and/or cellular characteristics of stem cell malignant transformation
A method for screening agent that preferentially affects a cancer stem cell relative to an isogenic non-cancer stem cell or its derivatives comprising:
- (a) administering a biologically active agent to a cancer stem cell and an isogenic non-cancer stem cell or its derivatives;
- (b) selecting an agent that exhibits a differential biological effect on the cancer stem cell than on the isogenic non-cancer stem cell or its derivatives.
A method of generating neural stem cells (NSC) from human embryonic stem cells (hESC), comprising:
- (a) culturing hESC;
- (b) disrupting cell cell contact by making single-cell suspension;
- (c) seeding single cells onto human xeno-free defined extracellular matrix (ECM) substrate;
- (d) disaggregating the hESC colonies and disrupting cell-cell contact;
- (e) growing disaggregated cells in a NSC culture medium in the presence of basic fibroblast growth factor (bFGF);
- (f) dissociating adherent cells and replating the dissociated cells onto the NSC culture medium in the presence of bFGF for several passages to obtain NSC.
Dependencies are inferred from the claim text.