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Robinton, DA and Daley, GQ. The promise of induced pluripotent stem cells in research and therapy. Nature 481: 295-305

Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature (Impact Factor: 42.35). 01/2012; 481(7381):295-305. DOI: 10.1038/nature10761
Source: PubMed

ABSTRACT The field of stem-cell biology has been catapulted forward by the startling development of reprogramming technology. The ability to restore pluripotency to somatic cells through the ectopic co-expression of reprogramming factors has created powerful new opportunities for modelling human diseases and offers hope for personalized regenerative cell therapies. While the field is racing ahead, some researchers are pausing to evaluate whether induced pluripotent stem cells are indeed the true equivalents of embryonic stem cells and whether subtle differences between these types of cell might affect their research applications and therapeutic potential.

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Available from: Daisy A Robinton, Feb 18, 2015
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    • "Although considered as an irreversible process e as an analogy to a rock spontaneously rolling downhill e the transition from pluripotent cells to terminally differentiated cells has recently been found to be reversible through a " reprogramming " process under certain " driving forces " , such as nuclear transfer [4], transcriptionlevel interference [5], and treatments with small molecules [6]. Such human induced pluripotent stem cells (hiPSCs), together with hESCs, are termed human pluripotent stem cells (hPSCs), holding great promise for studying human development and disease, regeneration of tissues and organs, and constructing patientspecific disease models for drug and toxicology screening [7] [8]. "
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    ABSTRACT: Human pluripotent stem cells (hPSCs) provide promising resources for regenerating tissues and organs and modeling development and diseases in vitro. To fulfill their promise, the fate, function, and organization of hPSCs need to be precisely regulated in a three-dimensional (3D) environment to mimic cellular structures and functions of native tissues and organs. In the past decade, innovations in 3D culture systems with functional biomaterials have enabled efficient and versatile control of hPSC fate at the cellular level. However, we are just at the beginning of bringing hPSC-based regeneration and development and disease modeling to the tissue and organ levels. In this review, we summarize existing bioengineered culture platforms for controlling hPSC fate and function by regulating inductive mechanical and biochemical cues coexisting in the synthetic cell microenvironment. We highlight recent excitements in developing 3D hPSC-based in vitro tissue and organ models with in vivo-like cellular structures, interactions, and functions. We further discuss an emerging multifaceted mechanotransductive signaling network - with transcriptional coactivators YAP and TAZ at the center stage - that regulate fates and behaviors of mammalian cells, including hPSCs. Future development of 3D biomaterial systems should incorporate dynamically modulated mechanical and chemical properties targeting specific intracellular signaling events leading to desirable hPSC fate patterning and functional tissue formation in 3D. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 06/2015; 52. DOI:10.1016/j.biomaterials.2015.01.078 · 8.31 Impact Factor
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    • "Thus, approaches for closely mimicking stem cell niches may substantially increase the quality and efficiency of iPSC expansion and directed lineage specification. Such advancement will further enrich our understanding of iPSC biology and facilitate the development of new therapeutics (e.g. via establishment of patientspecific disease models), as well as advance iPSC-based cell replacement therapies (Robinton & Daley, 2012). Biomaterials—materials selected or designed to interact with biological systems (Williams, 2009)—offer a unique and appealing strategy to advance iPSC research. "
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    ABSTRACT: Derived from any somatic cell type and possessing unlimited self-renewal and differentiation potential, induced pluripotent stem cells (iPSCs) are poised to revolutionize stem cell biology and regenerative medicine research, bringing unprecedented opportunities for treating debilitating human diseases. To overcome the limitations associated with safety, efficiency, and scalability of traditional iPSC derivation, expansion, and differentiation protocols, biomaterials have recently been considered. Beyond addressing these limitations, the integration of biomaterials with existing iPSC culture platforms could offer additional opportunities to better probe the biology and control the behavior of iPSCs or their progeny in vitro and in vivo. Herein, we discuss the impact of biomaterials on the iPSC field, from derivation to tissue regeneration and modeling. Although still exploratory, we envision the emerging combination of biomaterials and iPSCs will be critical in the successful application of iPSCs and their progeny for research and clinical translation. © 2015 The Authors.
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    • "Although considered as an irreversible process e as an analogy to a rock spontaneously rolling downhill e the transition from pluripotent cells to terminally differentiated cells has recently been found to be reversible through a " reprogramming " process under certain " driving forces " , such as nuclear transfer [4], transcriptionlevel interference [5], and treatments with small molecules [6]. Such human induced pluripotent stem cells (hiPSCs), together with hESCs, are termed human pluripotent stem cells (hPSCs), holding great promise for studying human development and disease, regeneration of tissues and organs, and constructing patientspecific disease models for drug and toxicology screening [7] [8]. "
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    ABSTRACT: During embryogenesis and tissue maintenance and repair in an adult organism, a myriad of stem cells are regulated by their surrounding extracellular matrix (ECM) enriched with tissue/organ-specific nanoscale topographical cues to adopt different fates and functions. Attributed to their capability of self-renewal and differentiation into most types of somatic cells, stem cells also hold tremendous promise for regenerative medicine and drug screening. However, a major challenge remains as to achieve fate control of stem cells in vitro with high specificity and yield. Recent exciting advances in nanotechnology and materials science have enabled versatile, robust, and large-scale stem cell engineering in vitro through developments of synthetic nanotopographical surfaces mimicking topological features of stem cell niches. In addition to generating new insights for stem cell biology and embryonic development, this effort opens up unlimited opportunities for innovations in stem cell-based applications. This review is therefore to provide a summary of recent progress along this research direction, with perspectives focusing on emerging methods for generating nanotopographical surfaces and their applications in stem cell research. Furthermore, we provide a review of classical as well as emerging cellular mechano-sensing and -transduction mechanisms underlying stem cell nanotopography sensitivity and also give some hypotheses in regard to how a multitude of signaling events in cellular mechanotransduction may converge and be integrated into core pathways controlling stem cell fate in response to extracellular nanotopography.
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