This article discusses these issues and suggests a framework that may assist their consideration. Since the cells so generated have a very small potential to generate an 'embryo' and since the production of the cell lines requires destruction of that 'embryo', a further ethical issue arises. The development of alternative techniques that enable the generation of pluripotent stem cells from adult cells has opened new avenues of research but the generation of such cells has again been controversial since it requires the use of human eggs, using a technique called somatic cell nuclear transfer. 2012 Dec 7 151(6):1151-4.The search for sources of human stem cells has become a controversial topic from an ethical point of view primarily as it has required the destruction of human embryos. 2013 Jan 23(1):33-48.Ĭellular alchemy and the golden age of reprogramming. 2013 64:277-90.Ī blueprint for engineering cell fate: current technologies to reprogram cell identity. Reprogrammed cells for disease modeling and regenerative medicine. Origins and implications of pluripotent stem cell variability and heterogeneity. Stem cell metabolism in tissue development and aging. 2013 Oct 17 502(7471):309-10.Ī chemical logic for reprogramming to pluripotency. A stem cell perspective on cellular engineering. Morris, Edroaldo Lummertz da Rocha, George Q. Cell 2014 August 14:158(4):889-902.ĬellNet: Network Biology Applied to Stem Cell Engineering. 2014 Dec 4 516(7529):56-61.ĭissecting Engineered Cell Types and Enhancing Cell Fate Conversion via CellNet. Kumar RM, Cahan P, Shalek AK, Satija R, DaleyKeyser AJ, Li H, Zhang J, Pardee K, Gennert D, Trombetta JJ, Ferrante TC, Regev A, Daley GQ, Collins JJ. Nature 2013 show that iPSC generated by reprogramming of adult mouse cells in vivo maintain a totipotent-like developmental potential and can contribute to extraembryonic tissues as well as embryonic tissues.ĭeconstructing transcriptional heterogeneity in pluripotent stem cells. These in vitro-reprogrammed iPSC are also mainly pluripotent. b) Somatic cells cultured in vitro can be reprogrammed by overexpression of reprogramming transcription factors. ESC rarely exhibit totipotent-like features such as the potential to form extraembryonic tissues. a) ESC derived from blastocysts, self-renew in culture and are pluripotent, giving rise to all cell types of the growing embryo. Pluripotent stem cells and their potential. Please see: 'CellNet: Network Biology Applied to Stem Cell Engineering' Cahan et al., Cell 2014 August 14 158(4): 903-15 'Dissecting Engineered Cell Types and Enhancing Cell Fate Conversion via CellNet' Morris et al., Cell 2014 August 14:158(4):889-902.ĭe Los Angeles & Daley, Nature 2013. We have generated CellNet ( ), a network biology-based computational platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. We also use these disease models to deliver curative cell transplants after genome editing using for example the CRISPR/Cas system. These iPSC represent personalized human cell culture models that enable studies of fundamental disease mechanisms and in vitro chemical screens to identify drugs. We have generated iPSC from somatic cells obtained from patients with genetic immune deficiency, hemoglobin disorders like sickle cell anemia, and bone marrow failure syndromes including Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, Diamond-Blackfan anemia, and Pearson’s syndrome. We have worked to improve the reprogramming method, to probe its mechanisms, and to assess how closely iPSC approximate embryo-derived stem cells. To reprogram somatic cells, we transfer genes responsible for the pluripotency of ESC into human fibroblasts or peripheral blood and derive cell lines that exhibit immortal self-renewal, multilineage differentiation potential in vitro, and teratoma formation in immunodeficient mice - currently the gold standard definition of human stem cell pluripotency. We employ mouse and human ESC to study basic aspects of tissue development, and we derive personalized, patient-derived iPSC via reprogramming from somatic cells obtained from patients with variety of diseases.

Thus, they are valuable tools for studying tissue formation and one day may provide a resource for cellular therapies. Pluripotent stem cells (embryonic stem cells, ESC, and induced pluripotent stem cells, iPSC) can generate any of the hundreds of distinct cell types in the body.

Pluripotent and totipotent