Myocardial survival signaling in response to stem cell transplantation.

BACKGROUND: Experimental human stem cell transplantation to the heart has begun, but the mechanisms underlying benefits seen in preclinical models, both at the site of cell injection and at more distant regions, remain uncertain. We hypothesize that these benefits can be best understood first at the level of key intracellular signaling cascades in the host myocardium, which can be responsible for functional and structural preservation of the heart. STUDY DESIGN: Western blot and ELISA were used to assess key pathways that regulate cardiac myocyte survival and hypertrophy in both the infarct/borderzone and remote myocardium of C57/B6 mouse hearts subjected to coronary artery ligation, with subsequent injection of either vehicle or bone marrow-derived adult mesenchymal stem cells (MSC). RESULTS: Improved left ventricular function with MSC transplantation was associated with a relative preservation of Akt phosphorylation (activation) and of phosphorylation of downstream mediators of cell survival and hypertrophy. There was no substantial difference in activation of mitogen-activated protein kinase p38, and activation of the antiapoptotic mitogen-activated protein kinase extracellular signal-regulated kinase was lower at 1 week after MSC treatment, but rose beyond controls by week 2. Similar changes were observed in both the infarct/borderzone and the remote myocardium. CONCLUSION: Stem cell transplantation in the post-MI murine myocardium is associated with preservation of Akt signaling. Together with a possible later increase in extracellular signal-regulated kinase activation, this signaling change might be responsible for cardioprotection. Additional focused investigation might identify elements in transplantation regimens that optimize this mechanism of benefit, and that can increase the likelihood of human clinical success.

National institutes of health funding for surgical research.

OBJECTIVE: The objective was to compare National Institutes of Health (NIH) funding rates and application success rates among surgeon and nonsurgeon-scientists over the past 2 decades. SUMMARY BACKGROUND DATA: Surgeons may be capable of accelerating the translation of basic research into new clinical therapies. Nevertheless, most surgeon-scientists believe they are at a disadvantage in competing for peer-reviewed funding, despite a recent emphasis on "translational science" by organizations such as the NIH. METHODS: We accessed databases from the NIH and the American Association of Medical Colleges. RESULTS: Although total competing NIH awards rose 79.2% from 5608 to 10,052, the much smaller number of surgical awards increased only by 41.4% from 157 to 222. There was a small but statistically significant difference between total NIH and surgical application success rates (29% vs. 25%, P < 0.01). However, the persistently low percent of NIH funding going to surgical investigators was due primarily to the very small number of surgical applications, and to a much smaller increase in the absolute number of applications over time (464 vs. 23,847). As a result, the number of grants per 100 faculty members was more than 4 times higher among nonsurgical than surgical faculties at US medical schools. CONCLUSION: NIH funding to academic surgeons is declining relative to their nonsurgical colleagues. This trend will likely be reversed only by an increase in the number of grant applications submitted by surgeon-scientists. Structural changes in surgical training programs, and in the economics of academic surgery, may support a greater contribution of surgeon-scientists to the success of translational research.