%0 Journal Article
%T Modeling to Optimize Terminal Stem Cell Differentiation
%A G. Ian Gallicano
%J Scientifica
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/574354
%X Embryonic stem cell (ESC), iPCs, and adult stem cells (ASCs) all are among the most promising potential treatments for heart failure, spinal cord injury, neurodegenerative diseases, and diabetes. However, considerable uncertainty in the production of ESC-derived terminally differentiated cell types has limited the efficiency of their development. To address this uncertainty, we and other investigators have begun to employ a comprehensive statistical model of ESC differentiation for determining the role of intracellular pathways (e.g., STAT3) in ESC differentiation and determination of germ layer fate. The approach discussed here applies the Baysian statistical model to cell/developmental biology combining traditional flow cytometry methodology and specific morphological observations with advanced statistical and probabilistic modeling and experimental design. The final result of this study is a unique tool and model that enhances the understanding of how and when specific cell fates are determined during differentiation. This model provides a guideline for increasing the production efficiency of therapeutically viable ESCs/iPSCs/ASC derived neurons or any other cell type and will eventually lead to advances in stem cell therapy. 1. Introduction Two decades of researching stem cells has brought us to a point where they are beginning to be used to treat or cure diseases. The ¡°big three¡± stem cell types that comprise the heart of research include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells (ASCs). Although the 1970s¨C1990s saw many exciting discoveries pertaining to mouse ESCs and various types of ASCs, the field lit up in the late 1990s with the discovery by James Thompson¡¯s group that human ESCs could be cultured in vitro. ESCs, which are derived from the inner cell mass (ICM) of blastocyst stage embryos, have the ability to undergo self-renewal and to differentiate into any of the three primary germ layers [1, 2]. This characteristic, that is, pluripotency, is the basis for the idea of stem cell therapies [3]. It is widely believed that by harnessing the power of ESC differentiation researchers can guide them into specific mature cell types that can be used to replace dead or damaged cells in various disease states. However, preliminary studies have shown limited success in producing large, pure populations of cells for use as potential therapies [4¨C8]. While ESCs, iPCs, and some ASCs are among the most promising treatments for heart failure, spinal cord injury, neurodegenerative diseases, and diabetes,
%U http://www.hindawi.com/journals/scientifica/2013/574354/