br Results br Discussion The goal of this study was

Results
Discussion The goal of this study was to define a quality-control standard rubric for assessing stem cell-derived cardiac myocytes. We chose a set of experimental measurements that provide insight into not only the expression profile of the bupropion hydrochloride but also morphological and functional characteristics that are intimately tied to the contractile function of cardiac tissues (Bursac et al., 2002; Feinberg et al., 2012; Kléber and Rudy, 2004). We utilized ventricular myocytes isolated from postnatal mouse hearts to serve as our reference standard for defining the target phenotype. However, an inherent limitation to using these cells is the presence of noncardiomyocytes, such as fibroblasts, endothelial cells, and smooth muscle cells, that may confound the interpretation of some experimental measurements, such as gene-expression profiling. It should also be noted that the mESC- and miPSC-derived cardiac myocytes used in this study were produced using a differentiation protocol that gives rise to a heterogeneous population of atrial, ventricular, and pacemaker-like cells, which may also make interpretation of certain measurements challenging. However, the proposed quality-assessment strategy is not dependent on any particular set of measurements and allows researchers the flexibility to choose the set of experimental measurements that best suits their needs. Using the experimental measurements described above and isolated neonatal ventricular myocytes as our reference phenotype, we developed a “quality index” that utilizes the magnitude and variance of these measurements to provide a numeric score indicating how closely the stem cell-derived myocytes match the characteristics of the neonatal cardiac myocytes. The combination of gene-expression, morphological, electrophysiological, and contractility measurements employed allowed us to pinpoint specific differences in the structural and functional properties of the mESC and miPSC engineered tissues versus the neonate tissues that have important implications for their utility in in vitro assays. Additional studies of the relationships between these measurements and the response of engineered cardiac tissues to compounds that have known effects on heart function may provide valuable insight into the combination of measurements that can most reliably determine the ability of stem cell-derived cardiac myocytes to adopt the desired phenotype. With a carefully chosen set of experimental parameters, this quality-assessment rubric may provide a reliable means to evaluate strategies for improving the differentiation of cardiac myocytes from stem cells and drive them toward a more mature phenotype (Cassino et al., 2012). Further, this quality index will not only allow researchers to identify the commercial stem cell-derived myocyte product lines that are most suitable for their needs, it may also serve the stem cell industry as a quality-assurance system for ensuring that batches released to customers faithfully recapitulate the desired phenotype.
Experimental Procedures
Acknowledgments
Introduction Permanent damage to the hair cells of the inner ear results in sensorineural hearing loss, leading to communication difficulties in a large percentage of the population. Hair cells are the receptor cells that transduce the acoustic stimulus. Regeneration of damaged hair cells could potentially yield a cure for a condition that currently has no therapies other than prosthetic devices. Although hair cells do not regenerate in the mammalian cochlea, new hair cells in lower vertebrates are generated from epithelial cells, called supporting cells, that surround hair cells (Balak et al., 1990; Raphael, 1992; Stone and Cotanche, 1994; Stone and Rubel, 2000; Warchol and Corwin, 1996). In this study, we found newly formed hair cells after loss of the original hair cells in the newborn mammalian cochlea. The differentiation of new hair cells in response to damage occurred spontaneously and without significant proliferation of supporting cells. Previous work had shown generation of supernumerary hair cells in embryonic and neonatal mammals (Doetzlhofer et al., 2009; Hayashi et al., 2008; Kiernan et al., 2005; Takebayashi et al., 2007; Yamamoto et al., 2006) after inhibition of Notch signaling, which blocks differentiation of hair cells in the embryo (Lanford et al., 1999; Yamamoto et al., 2006; Zine et al., 2000).