Early embryonic sensitivity to cyclophosphamide in cardiac differentiation from human embryonic stem cells.
Summary of "Early embryonic sensitivity to cyclophosphamide in cardiac differentiation from human embryonic stem cells."
Human embryonic stem cells (hESCs) can differentiate into tissue derivatives of all three germ layers in vitro and mimic the development of the embryo in vivo. In this article, we have investigated the potential of an hEHuman embryonic stem cells (hESCs) can differentiate into tissue derivatives of all three germ layers in vitro and mimic the development of the embryo in vivo. In this article, we have investigated the potential of an hESC-based assay for the detection of toxicity to cardiac differentiation in embryonic development. First of all, we developed the protocol of cardiac induction from hESCs according to our previous work and distinguished cardiac precursor cells and late mature cardiomyocytes from differentiated cells, demonstrated by the quantitative real-time PCR (Q-PCR), immunocytochemistry, and flow cytometry analysis. In order to test whether cyclophosphamide (CPA) induces developmental and celluar toxicity in human embryo, we exposed the differentiating cells from hESCs to CPA (a well-known proteratogen) at different stages. We have found that a high concentration of CPA could inhibit cardiac differentiation of hESCs. Two separate exposure intervals were used to determine the effects of CPA on cardiac precursor cells and late mature cardiomyocytes respectively. The cardiac precursor cells were sensitive to CPA in non-cytotoxic concentrations for the expression of the cardiac specific mRNA markers GATA-4, Nkx2.5 and TNNT2. Non-cytotoxic CPA concentrations did not affect the mRNA markers expression in late mature cardiomyocytes, indicating that cardiac precursors were more sensitive to CPA than late cardiomyocytes in cardiogenesis. We set up the in vitro developmental toxicity test model so as to reduce the number of test animals and expenses without compromising the safety of consumers and patients. Furthermore, such in vitro methods may be possibly suited to test a large number of chemicals than the classical employed in vivo tests.
Affiliation
Journal Details
This article was published in the following journal.
Name: Cell biology international
ISSN: 1095-8355
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21561436
- DOI: http://dx.doi.org/10.1042/CBI20110031
Medical and Biotech [MESH] Definitions
Embryonal Carcinoma Stem Cells
The malignant stem cells of TERATOCARCINOMAS, which resemble pluripotent stem cells of the BLASTOCYST INNER CELL MASS. The EC cells can be grown in vitro, and experimentally induced to differentiate. They are used as a model system for studying early embryonic cell differentiation.
Embryo, Mammalian
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Growth Differentiation Factor 2
A growth differentiation factor that plays a regulatory role as a paracrine factor for a diverse array of cell types during EMBRYONIC DEVELOPMENT and in the adult tissues. Growth differentiation factor 2 is also a potent regulator of CHONDROGENESIS and was previously referred to as bone morphogenetic protein 9.
Growth Differentiation Factor 10
A growth differentiation factor that is closely-related in structure to BONE MORPHOGENETIC PROTEIN 3. Growth differentiation factor 10 is found at high levels in BONE, however it plays an additional roles in regulating EMBRYONIC DEVELOPMENT.
Cyclophosphamide
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
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