In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain

2008 ◽  
Vol 210 (2) ◽  
pp. 656-670 ◽  
Author(s):  
Michelle Hedrick Theus ◽  
Ling Wei ◽  
Lin Cui ◽  
Kevin Francis ◽  
Xinyang Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Survival ◽  
Rat Brain ◽  
Embryonic Stem ◽  
Hypoxic Preconditioning

High-content screening of feeder-free human embryonic stem cells to identify pro-survival small molecules

2010 ◽  
Vol 432 (1) ◽  
pp. 21-35 ◽  
Author(s):  
Paul D. Andrews ◽  
Melissa Becroft ◽  
Anders Aspegren ◽  
Jane Gilmour ◽  
Martyn J. James ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Survival ◽  
Small Molecules ◽  
Protein Kinases ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Basic Research ◽  
Rock Inhibitor

The propensity of human embryonic stem cells to die upon enzymatic disaggregation or low-density plating is an obstacle to their isolation and routine use in drug discovery and basic research. Equally, the very low rate of establishment of implanted cells hinders cell therapy. In the present study we have developed a high-content assay for human embryonic stem cell survival and used this to screen a range of libraries of ‘lead-like’ small molecules and known bioactives. From this we identified 18 confirmed hits with four structural classes being represented by multiple compounds: a series of 5-(acyl/alkyl-amino)indazoles, compounds with a 4-(acylamino)pyridine core, simple N6,N6-dialkyladenines and compounds with a 5-(acylamino)indolinone core. In vitro kinase profiling indicated that the ROCK (Rho-associated kinase)/PRK2 (protein kinase C-related kinase 2) protein kinases are of pivotal importance for cell survival and identified previously unreported compound classes that inhibited this important biological activity. An evaluation using an extensive panel of protein kinases showed that six of our hit compounds exhibited better selectivity for ROCK inhibition than the routinely used commercially available ROCK inhibitor Y-27632. In this screen we also identified the K+-ATP channel opener pinacidil and show that it probably promotes cell survival, by ‘off-target’ inhibition of ROCK/PRK2. We have therefore identified novel pro-survival compounds of greater specificity, equivalent potency and reduced toxicity relative to the routinely employed ROCK inhibitor Y-27632.

GATA-1 and Erythropoietin Cooperate to Promote Erythroid Cell Survival by Regulating bcl-xL Expression

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 87-96 ◽  
Author(s):  
Todd Gregory ◽  
Channing Yu ◽  
Averil Ma ◽  
Stuart H. Orkin ◽  
Gerd A. Blobel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Survival ◽  
Embryonic Stem ◽  
Erythroid Cell ◽  
Erythroid Cells ◽  
Downstream Effector ◽  
Apoptotic Protein ◽  
Related Proteins

The transcription factor GATA-1 is essential for normal erythropoiesis. By examining in vitro–differentiated embryonic stem cells, we showed previously that in the absence of GATA-1, committed erythroid precursors fail to complete maturation and instead undergo apoptosis. The mechanisms by which GATA-1 controls cell survival are unknown. Here we report that in erythroid cells, GATA-1 strongly induces the expression of the anti-apoptotic protein bcl-xL, but not the related proteins bcl-2 and mcl-1. Consistent with a role for bcl-xL in mediating GATA-1–induced erythroid cell survival, in vitro–differentiated bcl-xL−/− embryonic stem cells fail to generate viable mature definitive erythroid cells, a phenotype resembling that of GATA-1 gene disruption. In addition, we show that erythropoietin, which is also required for erythroid cell survival, cooperates with GATA-1 to stimulate bcl-xL gene expression and to maintain erythroid cell viability during terminal maturation. Together, our data show that bcl-xL is essential for normal erythroid development and suggest a regulatory hierarchy in which bcl-xL is a critical downstream effector of GATA-1 and erythropoietin-mediated signals.

scholarly journals Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro

2021 ◽  
Author(s):  
Eun-Young Shin ◽  
Seah Park ◽  
Won Yun Choi ◽  
Dong Ryul Lee
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Male Hypogonadism ◽  
Testosterone Levels ◽  
Sequence Of Events ◽  
Short Period ◽  
Molecular Compounds

Abstract Background: Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males. Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate in vitro. Therefore, there is a need for an alternative source of LCs. Methods: To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. Results: HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. Conclusion: We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism.

scholarly journals Creation of Engineered Cardiac Tissue In Vitro From Mouse Embryonic Stem Cells

Circulation ◽  
2006 ◽  
Vol 113 (18) ◽  
pp. 2229-2237 ◽  
Author(s):  
Xi-Min Guo ◽  
Yun-Shan Zhao ◽  
Hai-Xia Chang ◽  
Chang-Yong Wang ◽  
Ling-Ling E ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cardiac Tissue ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells

Differentiation of E14 Mouse Embryonic Stem Cells into Thyrocytes In Vitro

Thyroid ◽  
2010 ◽  
Vol 20 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Ningyi Jiang ◽  
Yingying Hu ◽  
Xiongying Liu ◽  
Yanfeng Wu ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells
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