Advancements in reprogramming strategies for the generation of induced pluripotent stem cells

Abstract

Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells has emerged as an invaluable method for generating patient-specific stem cells of any lineage without the use of embryonic materials. Following the first reported generation of iPS cells from murine fibroblasts using retroviral transduction of a defined set of transcription factors, various new strategies have been developed to improve and refine the reprogramming technology. Recent developments provide optimism that the generation of safe iPS cells without any genomic modification could be derived in the near future for the use in clinical settings. This review summarizes current and evolving strategies in the generation of iPS cells, including types of somatic cells for reprogramming, variations of reprogramming genes, reprogramming methods, and how the advancement iPS cells technology can lead to the future success of reproductive medicine.

Clonal genetic and hematopoietic heterogeneity among human-induced pluripotent stem cell lines

“…These differences may derive from donor-specific properties related to the cell type of origin or baseline genotype. In addition, dissimilar reprogramming strategies 7 and the persistence 8 or reactivation of reprogramming transgenes 5 may alter the properties of iPSCs. Finally, acquired chromosomal aberrations, including point mutations or copy number variations (CNVs) in iPSCs with apparently normal karyotypes, could cause phenotype variation.…”

Design and Production of mRNA-based Gene Vectors for Therapeutic Reprogramming of Cell Fate

“…One more practical option is the employment of a transformation-deficient reprogramming-competent mutant version of c-Myc [38]. Various source cells for the generation of iPS cells are expected to require different optimal combinations of reprogramming developmental factors [39,40].…”

Induced Pluripotent Stem Cells and Their Implication for Biomedical Sciences

“…However, adenovirus is generally rather poor at gene transfer. It is also very difficult to control the level of gene expression infected cell (Lai et al, 2011;Patel and Yang, 2010).…”

“…They also exhibit prolonged expression of the reprogramming genes in target cells. Nevertheless, the reprogramming efficiency of this approach was extremely low (Lai et al, 2011;Medvedev et al, 2010;Yu et al, 2011). The piggyBac system-is promising system used for iPSCs production without any modification of the host genome based on DNA transposons.…”

“…The efficiency of production is around 0,001%, which is one order lower than by using retroviral vectors. In particular, the concentration of the individual factors needs to be calibrated to approximate normal endogenous level (Kim et al, 2009;Lai et al, 2011;Wong and Chiu, 2011). Yakubov et al (2010) reported the use of in vitroproduced mRNA encoding for Oct4, Lin28, Sox2 and Nanog for reprogramming of human foreskin fibroblasts to generate RNA-produced iPSCs (RiPSCs).…”