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The gene expression profiles of induced pluripotent stem cells (iPSCs) generated by a non-integrating method are more similar to embryonic stem cells than those of iPSCs generated by an integrating method.

ABSTRACT: Induced pluripotent stem cells (iPSCs) obtained by the ectopic expression of defined transcription factors have tremendous promise and therapeutic potential for regenerative medicine. Many studies have highlighted important differences between iPSCs and embryonic stem cells (ESCs). In this work, we used meta-analysis to compare the global transcriptional profiles of human iPSCs from various cellular origins and induced by different methods. The induction strategy affected the quality of iPSCs in terms of transcriptional signatures. The iPSCs generated by non-integrating methods were closer to ESCs in terms of transcriptional distance than iPSCs generated by integrating methods. Several pathways that could be potentially useful for studying the molecular mechanisms underlying transcription factor-mediated reprogramming leading to pluripotency were also identified. These pathways were mostly associated with the maintenance of ESC pluripotency and cancer regulation. Numerous genes that are up-regulated during the induction of reprogramming also have an important role in the success of human preimplantation embryonic development. Our results indicate that hiPSCs maintain their pluripotency through mechanisms similar to those of hESCs.

SUBMITTER: Liu Y

PROVIDER: S-EPMC3459422 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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The gene expression profiles of induced pluripotent stem cells (iPSCs) generated by a non-integrating method are more similar to embryonic stem cells than those of iPSCs generated by an integrating method.

Liu Yajun Y Cheng De D Li Zhenzhen Z Gao Xing X Wang Huayan H

Genetics and molecular biology 20120726 3

Induced pluripotent stem cells (iPSCs) obtained by the ectopic expression of defined transcription factors have tremendous promise and therapeutic potential for regenerative medicine. Many studies have highlighted important differences between iPSCs and embryonic stem cells (ESCs). In this work, we used meta-analysis to compare the global transcriptional profiles of human iPSCs from various cellular origins and induced by different methods. The induction strategy affected the quality of iPSCs in ...[more]

PMID: 23055811

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Project description:BACKGROUND:The discovery of induced pluripotent stem cells (iPSCs) opened the possibilities for reprogramming cells back to a pluripotent state. Because of no apparent ethical issues connected with donation and derivation of biomaterial, iPSCs are considered as a research alternative to ethically highly disputed human embryonic stem cells (hESCs). However, the unique character of iPSCs leads to numerous ethical considerations, which mainly concern the issue of donor information and consent for the use of biospecimen in research and drug evaluation. METHODS:For the purpose of this analysis, we conducted a review of the literature in the PubMed/MEDLINE and Web of Science databases. The search algorithm led to the identification of 1461 results. After removing duplicates and screening of title and abstract, 90 articles were found to be relevant to the study's objective. Full texts of these articles were apprised and 62 articles were excluded at this step for not properly addressing the study's objective. In the final step, 28 articles were included in the analysis. Analyzed were both research and non-research manuscripts published in peer-reviewed journals. RESULTS:In the case of iPSC research, the information process should be guided by general frameworks established for research on human subjects but also by specific characteristics of iPSCs. We determined four main domains and 12 thematic subdomains that should be included in donor information. Our results show that majority of authors agree to the content of information with regard to the areas of general information, storage of cells, and protection of privacy. Two main issues that are discussed in the literature are donor's consent for use in future studies and the process of donor information. CONCLUSIONS:Given the unique character of iPSCs and the possibility of their various uses in the future, the content of donor information should contain specific information central to iPSC research. Effective methods of communicating information to donors should combine written and oral information with the possible use of multimedia.

Project description:RATIONALE:Extracellular vesicles (EVs) are tiny membrane-enclosed droplets released by cells through membrane budding or exocytosis. The myocardial reparative abilities of EVs derived from induced pluripotent stem cells (iPSCs) have not been directly compared with the source iPSCs. OBJECTIVE:To examine whether iPSC-derived EVs can influence the biological functions of cardiac cells in vitro and to compare the safety and efficacy of iPSC-derived EVs (iPSC-EVs) and iPSCs for cardiac repair in vivo. METHODS AND RESULTS:Murine iPSCs were generated, and EVs isolated from culture supernatants by sequential centrifugation. Atomic force microscopy, high-resolution flow cytometry, real-time quantitative RT-PCR, and mass spectrometry were used to characterize EV morphology and contents. iPSC-EVs were enriched in miRNAs and proteins with proangiogenic and cytoprotective properties. iPSC-EVs enhanced angiogenic, migratory, and antiapoptotic properties of murine cardiac endothelial cells in vitro. To compare the cardiac reparative capacities in vivo, vehicle, iPSCs, and iPSC-EVs were injected intramyocardially at 48 hours after a reperfused myocardial infarction in mice. Compared with vehicle-injected mice, both iPSC- and iPSC-EV-treated mice exhibited improved left ventricular function at 35 d after myocardial infarction, albeit iPSC-EVs rendered greater improvement. iPSC-EV injection also resulted in reduction in left ventricular mass and superior perfusion in the infarct zone. Both iPSCs and iPSC-EVs preserved viable myocardium in the infarct zone, whereas reduction in apoptosis was significant with iPSC-EVs. iPSC injection resulted in teratoma formation, whereas iPSC-EV injection was safe. CONCLUSIONS:iPSC-derived EVs impart cytoprotective properties to cardiac cells in vitro and induce superior cardiac repair in vivo with regard to left ventricular function, vascularization, and amelioration of apoptosis and hypertrophy. Because of their acellular nature, iPSC-EVs represent a safer alternative for potential therapeutic applications in patients with ischemic myocardial damage.

Dataset Information

The gene expression profiles of induced pluripotent stem cells (iPSCs) generated by a non-integrating method are more similar to embryonic stem cells than those of iPSCs generated by an integrating method.

Publications

The gene expression profiles of induced pluripotent stem cells (iPSCs) generated by a non-integrating method are more similar to embryonic stem cells than those of iPSCs generated by an integrating method.

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