Cell reprogramming is a progress in which the memory of a mature cell is erased and then the cell develops novel phenotype and function; ultimately, the fate of the cell changes. Cell reprogramming usually occurs at genes expression levels that no genomic DNA sequence change will be involved. By changing the programs of the genetic expressions of cells in terms of space and time, cell reprogramming alters the differentiation of cells and thus produces the required cells. Further research on cells reprogramming will elucidate the mechanisms that govern the cell development, and thus provides more information of the sources of seed cells used for regeneration medicine. More cells differentiated from many terminally differentiated cells will be obtained, which is extremely important for the understanding of molecular differentiation and for the development of cell replacement therapy. This article summarizes the classification, influencing factors, approaches and latest advances of cells reprogramming.
Animals ; Cell Dedifferentiation ; genetics ; Cell Differentiation ; genetics ; Cellular Reprogramming ; Gene Expression ; Humans ; Nuclear Transfer Techniques

Embryonic stem (ES) cells have the unique capacity to proliferate extensively and maintain the potential to differentiate into advanced derivatives of all three primary germ layers. ES cell lines can also be generated from human blastocyst embryos and are considered promising donor sources for cell transplantation therapies for diseases such as juvenile diabetes, Parkinson's disease, and heart failure. However, as for organ transplants, tissue rejection remains a significant concern for ES cell transplantation. Another concern is the use of human embryos. One possible means to avoid these issues is by reprogramming the nuclei of differentiated cells to ES cell-like, pluripotent cells. This review discusses the potential of these strategies to generate tailor-made pluripotent stem cells and the role of transcription factors in the reprogramming process.
Cell Culture Techniques ; Cell Differentiation ; physiology ; Cells, Cultured ; Cellular Reprogramming ; Humans ; Nuclear Transfer Techniques ; Pluripotent Stem Cells ; cytology

Nuclear transfer (NT) is a new cloning technology developed in recent years. NT methods consist of electrofusion, NT mediated by polyethylene glycol (PEG) and microinjection. The success of somatic nuclear transfer depends on the source of donor nucleus, developmental stage of recipient cytoplasts, cell cycle synchrony of donor nucleus. Different methods of harvesting cells have effect on the efficiency of NT. The somatic nucleus will be reprogrammed after NT and will restore a totipotent state in order to undergo development.
Animals ; Cell Differentiation ; physiology ; Cell Division ; Cells, Cultured ; Cellular Reprogramming ; Cloning, Organism ; Embryo Transfer ; Humans ; Microinjections ; Nuclear Transfer Techniques ; trends ; Oocytes ; cytology ; physiology

Nuclear reprogramming is described as a molecular switch, triggered by the conversion of one cell type to another. Several key experiments in the past century have provided insight into the field of nuclear reprogramming. Previously deemed impossible, this research area is now brimming with new findings and developments. In this review, we aim to give a historical perspective on how the notion of nuclear reprogramming was established, describing main experiments that were performed, including (1) somatic cell nuclear transfer, (2) exposure to cell extracts and cell fusion, and (3) transcription factor induced lineage switch. Ultimately, we focus on (4) transcription factor induced pluripotency, as initiated by a landmark discovery in 2006, where the process of converting somatic cells to a pluripotent state was narrowed down to four transcription factors. The conception that somatic cells possess the capacity to revert to an immature status brings about huge clinical implications including personalized therapy, drug screening and disease modeling. Although this technology has potential to revolutionize the medical field, it is still impeded by technical and biological obstacles. This review describes the effervescent changes in this field, addresses bottlenecks hindering its advancement and in conclusion, applies the latest findings to overcome these issues.
Animals ; Cell Fusion ; Cell Lineage ; genetics ; Cellular Reprogramming ; genetics ; Humans ; Nuclear Transfer Techniques ; Pluripotent Stem Cells ; cytology ; metabolism ; Transcription Factors ; metabolism

Tissue damage induces cells into reprogramming-like cellular state, which contributes to tissue regeneration. However, whether factors promoting the cell reprogramming favor tissue regeneration remains elusive. Here we identified combination of small chemical compounds including drug cocktails robustly promoting in vitro cell reprogramming. We then administrated the drug cocktails to mice with acute liver injuries induced by partial hepatectomy or toxic treatment. Our results demonstrated that the drug cocktails which promoted cell reprogramming in vitro improved liver regeneration and hepatic function in vivo after acute injuries. The underlying mechanism could be that expression of pluripotent genes activated after injury is further upregulated by drug cocktails. Thus our study offers proof-of-concept evidence that cocktail of clinical compounds improving cell reprogramming favors tissue recovery after acute damages, which is an attractive strategy for regenerative purpose.
Animals ; Cellular Reprogramming ; drug effects ; Cellular Reprogramming Techniques ; methods ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Mice

Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our understanding of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on reprogramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for various applications, such as disease modeling and cell-based transplantation, but also hold great promise to be further developed as drugs to stimulate patients' endogenous cells to repair and regenerate in vivo. Here we will focus on chemical approaches for generating induced pluripotent stem cells, neurons, cardiomyocytes, hepatocytes and pancreatic β cells. Significantly, the rapid and exciting advances in cellular reprogramming by small molecules will help us to achieve the long-term goal of curing devastating diseases, injuries, cancers and aging.
Animals ; Cellular Reprogramming ; Cellular Reprogramming Techniques ; methods ; Humans ; Induced Pluripotent Stem Cells

To establish a co-culture system of nuclear transferred embryos in bovine, effects of co-culture cell types, passages and cryopreservation as well as addition of BFF or FBS were investigated. The results showed that embryos co-cultured with oviductal epithelial cell and granulosa cell achieved significantly higher blastocyst rate compared with the control group (P < 0.05) and co-cultured with oviductal epithelial cell had more embryo cell number than those with granulosa cell. Passages of co-culture cells significantly affected the blastocyst rate and embryo cell number (P < 0.05), and cryopreservation decreased the blastocyst rate and embryo cell number remarkably. Supplemention of BFF increased blastocyste rate significantly (P < 0.05). In conclusion, co-cultured with fresh primary oviductal epithelial cell along with addition of 10% BFF in SOFaa could improve development of nuclear transferred bovine embryo in vitro.
Animals ; Cattle ; Cellular Reprogramming ; Cloning, Organism ; methods ; Coculture Techniques ; Culture Media ; Embryo, Mammalian ; cytology ; drug effects ; Embryonic Development ; Epithelial Cells ; cytology ; drug effects ; Fallopian Tubes ; cytology ; Female ; Granulosa Cells ; cytology ; drug effects ; Nuclear Transfer Techniques

The slow progress in clinical applications of stem cells and the bewildering mechanisms involved have puzzled many researchers. Recently, the increasing evidences have indicated that cells have superior plasticity in vivo or in vitro, spontaneously or under extrinsic specific inducers. The concept of stem cells may be challenged, or even replaced by the concept of cell plasticity when cell reprogramming technology is progressing rapidly. The characteristics of stem cells are manifestations of cellular plasticity. Incorrect understanding of the concept of stem cells hinders the clinical application of so-called stem cells. Understanding cellular plasticity is important for understanding and treating disease. The above issues will be discussed in detail to prove the reconceptualization of stem cells from cellular plasticity.
Cell Plasticity ; Cellular Reprogramming ; In Vitro Techniques ; Plastics ; Stem Cells

The genome instability and tumorigenicity of induced pluripotent stem cells (iPSC) hinder their great potentials for clinical application. Using episomal vectors to generate iPSC is the best way to solve safety issues at present. This method is simple and the exogenous gene was not integrated into the host genome. However, the reprogramming efficiency for this method is very low and thus limits its usage. This study was purposed to improve episomal method for generating induced pluripotent stem cells from cord blood mononuclear cells (CB MNC), to establish integration-free iPSC technology system, and to lay the foundation for individualized iPSC for future clinical uses. To improve the reprogramming efficiency for iPSC, episomal method was used at various combinations of episomal vectors, pre-stimulating culture mediums and oxygen condition were tested to optimize the method. The results showed that using erythroid culture medium for culturing 8 days, transfecting with episomal vectors with SFFV (spleen focus forming virus) promoter under the hypoxic condition (3%), CB MNC could be mostly efficiently reprogrammed with the efficiency 0.12%. Furthermore, the results showed that erythroblasts (CD36(+)CD71(+)CD235a(low)) were the cells that are reprogrammed with high efficiency after culture for 8 days. It is concluded that a highly efficient and safe method for generation of integration-free iPSC is successfully established, which is useable in clinical study.
Cell Culture Techniques ; methods ; Cellular Reprogramming ; Genetic Vectors ; Humans ; Induced Pluripotent Stem Cells ; cytology ; Plasmids ; Transfection

Since Yamanaka successfully reprogrammed murine fibroblasts into iPSCs in 2006, iPSCs technology has drawn much attention worldwide. Although iPSCs provides tremendous possibilities for both basic research and regenerative medicine, it has meanwhile potential risks, e.g. tumorigenicity. Scientists, therefore, have made efforts in clarifying the mechanism of the cause for iPSCs tumorigenicity and the way how to reduce the risk. The results of some researches reveal some of tumorigenic factors, e.g. the partial similarity of gene expression profiles between cancer cells and iPSCs, the accumulation of the genetic damages in the course of reprogramming process, and mutation in the cellular culture. As a consequence, numerous methods for reducing iPSCs tumorigenicity have been explored, such as minimized use of the reprogramming factors at the controlled manner, and the selection of the expression vector or parental cells. In this paper, the cause of iPSCs tumorigenicity and the current achievements on preventing iPSCs tumorigenesis are reviewed.
Animals ; Carcinogenesis ; Cell Culture Techniques ; Cellular Reprogramming ; Fibroblasts ; Genetic Vectors ; Humans ; Induced Pluripotent Stem Cells ; cytology ; Mice ; Mutation ; Transcriptome