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Stem cells are characterized by their ability to self-renew and to generate a diverse range of physiological cell types (Singec et al., Annu Rev Med. 2007; 58:313–328). In mammals, stem cells found in the mature organism (somatic stem cells) generate progeny of a specific cell lineage or tissue type (multipotency). For example, a hematopoietic stem cell gives rise to the cell lineages found in bone marrow and blood, while a central nervous system (CNS) neural stem cell generates neurons, oligodendrocytes, and astroglia (Murry and Keller, Cell. 2008; 132:661–680). At an earlier developmental stage, embryonic stem (ES) cells obtained from the inner cell mass of blastocyst-stage embryos exhibit limitless capacity to self-renew and can give rise to any cell type of the organism, thereby defining pluripotency (Murry and Keller, Cell. 2008; 132:661–680; Singec et al. Annu Rev Med. 2007; 58:313–328). The term “totipotent” is reserved for cells that can also give rise to the trophoblast and extraembryonic tissue in vivo, such as the fertilized egg (zygote). These designations exemplify how differentiation toward a specific mature cell phenotype is accompanied by an increasingly limited spectrum of potential descendant cell types and by a diminished proliferative capacity (Yeo et al., Hum Reprod. 2008; 23:67–73) (Fig. 1 ). In addition, recent advances in reprogramming of adult somatic cell types into pluripotent cells (Takahashi et al., Cell. 2007; 131:861–872) are aimed at controlling the regulatory mechanisms that govern stemness and pluripotency, which may soon enable even more refined modulation of cell fate (Yeo et al., Hum Reprod. 2008; 23:67–73; Pruszak and Isacson, Development and engineering of dopamine neurons. Austin, TX: Landis Bioscience; 2008; Jaenisch and Young, Cell. 2008; 132:567–582). To achieve translation of stem cell biology into clinical applications, somatic, embryonic, and reprogrammed stem cell sources alike are presently being investigated. Despite the fast-paced progress of stem cell research as a field, many aspects of cell development in the dish are still not fully understood. To ensure appropriate patterning, signaling parameters for cell lineage specification need to be identified, and generating the phenotype of interest requires close monitoring and controlled modulation of the microenvironmental conditions in the dish.
We summarize universal principles, advancements, and ongoing challenges in deriving and characterizing therapeutic cell types from pluripotent and multipotent stem cells for clinical and scientific biomedical scenarios. Specifically, this overview illustrates the paradigm of neural stem cell differentiation and the application of microphysiometer systems to monitor and control conditions fostering the generation, maturation, and survival of specific neural cell populations aimed at treating neurological disease.
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- Neural Stem Cells: From Cell Fate and Metabolic Monitoring Toward Clinical Applications
Gerald A. Urban
- Springer Berlin Heidelberg