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Concept
Directed differentiation
Summary
Directed differentiation is a bioengineering methodology at the interface of stem cell biology, developmental biology and tissue engineering. It is essentially harnessing the potential of stem cells by constraining their differentiation in vitro toward a specific cell type or tissue of interest. Stem cells are by definition pluripotent, able to differentiate into several cell types such as neurons, cardiomyocytes, hepatocytes, etc. Efficient directed differentiation requires a detailed understanding of the lineage and cell fate decision, often provided by developmental biology.
During differentiation, pluripotent cells make a number of developmental decisions to generate first the three germ layers (ectoderm, mesoderm and endoderm) of the embryo and intermediate progenitors, followed by subsequent decisions or check points, giving rise to all the body's mature tissues. The differentiation process can be modeled as sequence of binary decisions based on probabilistic or stochastic models. Developmental biology and embryology provides the basic knowledge of the cell types' differentiation through mutation analysis, lineage tracing, embryo micro-manipulation and gene expression studies. Cell differentiation and tissue organogenesis involve a limited set of developmental signaling pathways. It is thus possible to direct cell fate by controlling cell decisions through extracellular signaling, mimicking developmental signals.
Directed differentiation is primarily applied to pluripotent stem cells (PSCs) of mammalian origin, in particular mouse and human cells for biomedical research applications. Since the discovery of embryonic stem (ES) cells (1981) and induced pluripotent stem (iPS) cells (2006), source material is potentially unlimited.
Historically, embryonic carcinoma (EC) cells have also been used. Fibroblasts or other differentiated cell types have been used for direct reprogramming strategies.
Cell differentiation involves a transition from a proliferative mode toward differentiation mode.
Official source
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