Small molecule screening with laser cytometry can be used to identify pro-survival molecules in human embryonic stem cells.

Differentiated cells from human embryonic stem cells (hESCs) provide an unlimited source of cells for use in regenerative medicine. The recent derivation of human induced pluripotent cells (hiPSCs) provides a potential supply of pluripotent cells that avoid immune rejection and could provide patient-tailored therapy. In addition, the use of pluripotent cells for drug screening could enable routine toxicity testing and evaluation of underlying disease mechanisms. However, prior to establishment of patient specific cells for cell therapy it is important to understand the basic regulation of cell fate decisions in hESCs. One critical issue that hinders the use of these cells is the fact that hESCs survive poorly upon dissociation, which limits genetic manipulation because of poor cloning efficiency of individual hESCs, and hampers production of large-scale culture of hESCs. To address the problems associated with poor growth in culture and our lack of understanding of what regulates hESC signaling, we successfully developed a screening platform that allows for large scale screening for small molecules that regulate survival. In this work we developed the first large scale platform for hESC screening using laser scanning cytometry and were able to validate this platform by identifying the pro-survival molecule HA-1077. These small molecules provide targets for both improving our basic understanding of hESC survival as well as a tool to improve our ability to expand and genetically manipulate hESCs for use in regenerative applications.

Systematic assessment and meta-analysis of the efficacy and safety of fasudil in the treatment of cerebral vasospasm in patients with subarachnoid hemorrhage.

PURPOSE: Cerebral vasospasm (CVS) is a frequent and unpredictable complication in patients with subarachnoid hemorrhage (SAH) and often leads to poor outcomes. This study was aimed at evaluating the efficacy and safety of fasudil in the treatment of CVS in patients with SAH. METHODS: A search was conducted using the full-text database of Chinese scientific journals, the Wanfang Database (January 1999 to November 2010), the Chinese Medical Association Digital Journal Database, PubMed, the Cochrane library, OVID, and EMBase (searching through November 2010). RESULTS: A total of 8 studies met the inclusion criteria. The incidence rates of symptomatic CVS and CVS confirmed by angiography among the patients in the fasudil group were only 48% (odds ratio [OR] = 0.48, 95% confidence interval [CI]: 0.32-0.72, P = 0.0005) and 40% (OR = 0.40, 95% CI: 0.24-0-67, P = 0.0004) respectively of that of the control group. The odds ratios of cerebral infarction for all cases and cerebral infarction for CVS cases in the fasudil group were only 50% (OR = 0.50, 95% CI: 0.34-0.76, P = 0.0009) and 43% (OR = 0.43, 95% CI: 0.26-0.70, P = 0.0008) respectively of that of the control group. CONCLUSIONS: Fasudil greatly reduces the occurrence of CVS and cerebral infarction in SAH patients, significantly improves the clinical outcomes of the patients (as assessed by the Glasgow Outcome Scale). Because of the limited number of trials and samples available for analysis, the conclusions from the present study still need to be validated with results from large randomized, controlled clinical trials.