Human pluripotent stem cell differentiation

Zhang J et al (2009) Functional cardiomyo-cytes derived from human induced pluripotent stem cells. Circ Res 104(4) e30-e41 Zwi L et al (2009) Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation 120(15) 1513-1523 Burridge PW et al (2012) Production of de novo cardiomyocytes human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10(l) 16-28 Rattman SJ et al (2011) Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and... 

P. W. Burridge, G. Keller, J. D. Gold, J. C. Wu, Production of de novo cardiomyocytes human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10, 16-28 (2012). 

Differentiation Methods for Human Pluripotent Stem Cell-Derived Cardiomyocytes... 

Yang L, Soonpaa MH, Adler ED et al (2008) Human cardiovascular progenitor cells develop from a KDR plus embryonic-stem-cell-derived population. Nature 453(7194) 524-526. Lian XJ, Hsiao C, Wilson G et al (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A 109(27) E1848-E1857... 

Lian XJ, Zhang JH, Azarin SM et al (2013) Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/beta-catenin signaling under frilly defined conditions. Nat Protoc 8(1) 162-175. Sirenko O, Crittenden C, Callamaras N et al (2013) Multiparameter in vitro assessment of compound effects on cardiomyocyte physiology using iPSC cells. J Biomol Screen 18(1) 39-53... 

Fig. 2 Human pluripotent stem cells (NT2 cell line) differentiated in neuronal culture (96DIV). Groups of neurons are linked by the dense network of neurites, positively stained against NF-200 (green) with cell nuclei co-stained by DAPI...

The currently available human brain endothelial cell lines do not provide enough paracellular restriction to be useful in permeability screens, even if their high throughput and ease of culture are of advantage. Another possibility would be to use human pluripotent stem cells, because it might constitute a new way of obtaining a reliable human in vitro BBB model if they can be made to differentiate into endothelial cells displaying the BBB phenotype in vivo. 

Zhang J et al (2012) Extracellular matrix promotes highly efficient cardiac differentiation of human pluripotent stem cells the matrix sandwich method. Circ Res 111 (9) 1125-1136... 

Fig. 4 Using Human Pluripotent Stem Cells for Disease Modeling. Patient-specific somatic cells (e.g. skin fibroblasts) can be reprogrammed into induced pluripotent stem cells (iPSCs) using specific genetic factors. Neuronal cells with specific disease phenotypes can be differentiated to neural stem cells. The development of in vitro cellular models based on patient-specific cells may lead to personalized medicine approaches with minimal side effects and improved pharmacological efficacy.

Kang, M. and Han, Y.-M. (2014) Differentiation of human pluripotent stem cells into nephron progenitor cells in a serum and feeder free system. PLoS One 9, e94888. 

Lam, A.Q., Freedman, B.S., Morizane, R., Lerou, P.H., Valerius, M.T., and Bonventre, J.V. (2014) Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers. J. Am. Soc. Nephrol. 25, 1211—1225. 

H. Kempf, R. Ohner, C. Kropp, M. Ruckert, M. Jara-Avaca, D. Robles-Diaz, A. Franke, D. A. EUiott, D. Wojciechowski, M. Fischer, Controlling expansion and cardiomyogenic differentiation of human pluripotent stem cells in scalable suspension culture. Stem Cell Rep 3, 1132—1146 (2014). 

Y. Lei, D. V. Schaffer, A fuUy defined and scalable 3D culture system for human pluripotent stem cell expansion and differentiation. Proc Natl Acad Sci USA 110, E5039-E5048 (2013). 

A race on the generation of stem cell-derived renal cells started in 2013. In January 2013 a protocol for the differentiation of hiPSC or hESC into IM was published (Mae et al., 2013). Odd-skipped related (OSR)l was used as the main IM marker, and up to 90% OSRO cells were obtained. More differentiated renal cell types were only obtained at low frequency, which was not sufficient for use of these cells in any application, including in vitro toxicology (Mae et al., 2013). However, briefly afterward the first protocol for the differentiation of human pluripotent stem cells (hPSC) into mature renal cells was published (Narayanan et al., 2013). This protocol was based on hESC, and the differentiated hESC-derived cells exhibited many features of HPTC and were therefore called HPTC-like cells. The hESC-derived HPTC-like cells were then directly used for the development of the first stem cell-based renal in vitro model for the prediction of DIN (Li et al., 2014). (This in vitro model will be described in more detail in the following.) Later in 2013 the race on the generation of stem cell-derived renal cells continued and various alternative protocols were developed (Lam et al., 2014 Xia et al., 2013 Kang and Han, 2014 Taguchi et al., 2014 Takasato et al., 2014) (Fig. 23.1). 

J. Bardy, A.K. Chen, YM. Lim, S. Wu, S. Wei, H. Weiping, K. Chan, S. Reuveny, and S.K. Oh, Microcarrier suspension cultures for high-density expansion and differentiation of human pluripotent stem cells to neural progenitor cells, Tissue Eng., Part C, Methods, 19 (2) 166-180, Feb. 2013. 

Kattman, S. J., A. D. Witty, M. Gagliardi et al. 2011. Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8(2) 228-40. 

The greatest impact of human pluripotent stem cells in the near term is their ability to provide a model system to study human development in vitro. For ethical and practical reasons, developmental biology relies on animal model systems and human cell lines or primary tissues. However, model systems do not always accurately recapitulate human development, and cell lines and primary tissue often behave differently in vitro than in vivo, and cannot access all stages of development. Human ESCs and iPSCs provide an in vitro model system to study development from the very earliest stages through terminal differentiation to specialized cells. Examples of disease modeling include generation of iPSCs... 

Leung HW, Chen A, Choo AB, Reuveny S, Oh SK. 2011. Agitation can induce differentiation of human pluripotent stem cells in microcarrier cultures. Tissue Eng Part C Methods 17(2) 165-72. 

Kogler, G., Sensken, S., Airey, J. A., et al. (2004), A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential, /. Exp. Med., 200(2), 123-135. 

Human embryonic stem cells were first collected in 1998 by two different research teams. The cells obtained from the inner cell mass of the blastocyst (4- to 5-day embryo) are embryonic stem cells (ESC) in contrast, cells cultured from the primordial germ cells of 5- to 9-week fetuses are embryonic germ cells (EGC). In the laboratory, ES or EG cells can proliferate indefinitely in an undifferentiated state but can also be manipulated to become specialized or partially specialized cell types, a process known as directed differentiation. Both ES and EG cells are pluripotent, meaning they have the potential to develop into more than 200 different known cell types. This class of human stem cells holds the promise of being able to repair or replace cells or tissues that are damaged or destroyed by many of our most devastating diseases and disabilities. 

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