Special Issue "Natural and Induced Pluripotency in Stem Cells"

Guest Editor
Dr. Paolo Cinelli
Institute of Laboratory Animal Science, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Website: http://www.ltk.uzh.ch/de/
E-Mail:
Phone: +41 44 635 54 61
Fax: +41 44 635 68 75
Interests: transcriptomics; microarrays; gene expression analysis; genotyping; molecular genetics; mouse genetics; transgenic technologies; embryonic stem cells; pluripotency

Dear Colleagues,

Cellular pluripotency is one of the most fascinating and promising research fields in biomedical research. The recent discovery that ordinary cells following the introduction of a small number of genes can acquire stem cell behaviors opens a new door for stem cell research and its application to therapeutic discovery. The exhaustive understanding of the molecular pathways controlling pluripotency and cellular reprogramming is essential for the development of effective and safe approaches to reprogram somatic cells towards a pluripotent state.
This Special Issue of the Journal Genes aims at presenting recent research and developments on this very exciting topic. Reviews and original papers presenting data on embryonic and induced pluripotent stem cells are welcome for this Special Issue. Special interest will be given to reports on genes and/or pathways involved in the establishment and maintenance of natural and acquired pluripotency, in controlling the global and local chromatin organization in pluripotent cells, and in triggering reprogramming in somatic and adult stem cells.

Dr. Paolo Cinelli
Guest Editor

Related Special Issue

Cancer Stem Cells in Cancers

Submission

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• embryonic stem cells
• induced pluripotent stem cells
• self renewal
• cell differentiation
• reprogramming
• gene expression regulation
• microRNAs
• epigenetics
• DNA methylation

Title: Different Techniques for the Derivation of Human Induced Pluripotent Stem Cells
Authors: Kazim H. Narsinh and Joseph C. Wu; E-Mail: kazimn@stanford.edu
Abstract: The successful derivation of human induced pluripotent stem cells (hiPSCs) by de-differentiation of somatic cells offers significant potential to overcome obstacles in the field of regenerative medicine. However, many questions remain regarding the optimal starting materials and methods to enable safe, efficient derivation of hiPSCs suitable for cellular transplantation. Initial reprogramming experiments were carried out using lentiviral or retroviral gene delivery methods. However, various non-viral methods that avoid permanent and random transgene insertion have since emerged as alternatives. These include transient DNA transfection approaches using transposons or minicircle plasmids, as well as protein transduction approaches. In addition, several small molecules have been found to significantly augment iPSC derivation efficiency, allowing the use of a smaller number of genes during pluripotency induction. Here, we review these various methods for the derivation of iPSCs with a focus on their ultimate clinical feasibility.

Type of Paper: Review
Title: Insights into the Mechanisms of Somatic Cell Reprogramming: What's in the Black Box?
Authors: L. David, P. Samavarchi-Tehrani, A. Golipour and J. Wrana
Affilliation: Samuel Lunenfeld Research Institute, 1070-600 University Avenue, Toronto, Ontario, M5G 1X5, Canada; E-Mail: ldavid@lunenfeld.ca (L.D.)
Abstract: Revival of cellular reprogramming in 2006 by generating induced pluripotent stem (iPS) cells from somatic cells has resulted in new opportunities for regenerative medicine and novel ways of modeling human diseases. Extensive research over the short time since the first iPS has yielded the ability to reprogram various cell types using a diverse range of methods. The duration, efficiency and safety of reprogramming have remained as a persistent limitation to achieving a robust experimental and therapeutic system. The field has worked to resolve these issues through technological advances using non-integrative approaches, factor replacement or complementation with microRNA, shRNA and drugs. Despite these advances, the mechanism underlying the reprogramming process remains poorly understood. However, through the use of inducible secondary systems, researchers have now been able to conduct more rigorous mechanistic experiments to decipher this complex process. In this review we will discuss some of the major recent findings in reprogramming pertaining to proliferation and cellular senescence, epigenetic and chromatin remodelling, and other complex cellular processes such as morphological changes and mesenchymal-to-epithelial transition. We will focus on the implications of the work done thus far and discuss unexplored areas in this rapidly expanding field.

Title: The Expanding Repertoire of Amniotic Fluid-derived Stem Cells
Authors: David L. Mack and Anthony Atala
Affiliation: The Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA; E-Mail: dmack@wfubmc.edu (D.L.M.)
Abstract: The severe shortage of donor organs available for transplantation limits the treatment options available for patients suffering from diseased and injured organs. Regenerative Medicine seeks to employ progenitor and stem cells, often coupled with biomaterials, to generate new, healthy tissues and organs. Human amniotic fluid has been utilized in prenatal diagnosis for many years.  There is now evidence that amniotic fluid contains subsets of stem cells that lie biologically somewhere between ES cells and adult somatic stem cells that are capable of maintaining prolonged undifferentiated proliferation as well as differentiate into multiple tissue lineages. One of the subsets of multipotential stem cells can be isolated through positive selection for cells expressing the membrane receptor c-kit that binds stem cell factor.  Roughly 1% of the cells present in amniotic fluid have been shown to be c-kit⁺. Single-cell clones of amniotic fluid-derived stem (AFS) cells show high self-renewal capacity with >300 population doublings, far exceeding Hayflick’s limit, and expand in vitro without the need for feeder layers. On the other hand, AFS cells do not form teratomas in vivo when implanted in immunodefficient mice, thereby making them a more attractive cell source for transplantation than modifed ES cells. Equally as important therapeutically, AFS cells have a normal karyotype at late passages, normal G₁ and G₂ cell cycle checkpoints and telomere length conservation.  Analysis of surface markers shows that AFS cells express embryonic markers such as SSEA4 and adult mesenchymal stem cell markers including CD29, CD44 (hyaluronan receptor), CD73, CD90, and CD105.  AFS cells can differentiate efficiently into mesenchymal lineages such as bone, cartilage, fat and muscle and, when cultured under specific inductive conditions, express markers of endodermal (liver, pancreas) and ectodermal (nerve) lineages. Clinical application research with AFS cells focuses on cellular therapy for bone and cartilage loss, cardiac ischemia, diabetes and immune diseases. Studies have shown that AFS cells in alginate gel formed a calcified mass that maintained its volume and density for several weeks in vivo. Similar results were obtained with AFS cell-derived bioengineered cartilage. AFS cells differentiate in vitro to cardiomyocyte-like cells and improve cardiac function upon injection into ischemic heart muscle, where they showed cellular communication with the host cells. AFS cells, genetically modified to express genes that control pancreatic development, express pancreatic-specific genes such as insulin and glucagon. In addition, a growing body of literature is now demonstrating the added benefit of immunomodulatory characteristics of AFS cells. The ease of maintenance, proliferation, and differentiation of the amniotic progenitor cells will enable additional uses of these cells for investigation into developmental pathways and drug screening.  Whether AFS cells engraft and replace damaged tissue or augment endogenous regeneration through the secretion of trophic factors, or in certain circumstances do a combination of both, it is clear that AFS cells have a promising future in regenerative medicine. This review will focus on the wide range of potential clinical applications of AFS cells and our current understanding of what makes them an appealing stem cell source.