Clinical trials of bone marrow mesenchymal stem cell (MSC) therapy have thus far demonstrated moderate and inconsistent benefits, indicating an urgent need to improve therapeutic efficacy. Although administration of sufficient cells is necessary to achieve maximal therapeutic benefits, documented MSC clinical trials have largely relied on injections of ∼1 × 10(6) cells/kg, which appears too low to elicit a robust therapeutic response according to published preclinical studies. However, repeated cell passaging necessary for large-scale expansion of MSC causes cellular senescence and reduces stem cell potency. Using the RNA mimetic polyinosinic-polycytidylic acid [poly(I:C)] to engage MSC Toll-like receptor 3 (TLR3), we found that poly(I:C), signaling through multiple mitogen-activated protein kinase pathways, induced therapeutically relevant trophic factors such as interleukin-6-type cytokines, stromal-derived factor 1, hepatocyte growth factor, and vascular endothelial growth factor while slightly inhibiting the proliferation and migration potentials of MSC. At the suboptimal injection dose of 1 × 10(6) cells/kg, poly(I:C)-treated MSC, but not untreated MSC, effectively stimulated regeneration of the failing hamster heart 1 mo after cell administration. The regenerating heart exhibited increased CD34(+)/Ki67(+) and CD34(+)/GATA4(+) progenitor cells in the presence of decreased inflammatory cells and cytokines. Cardiac functional improvement was associated with a ∼50% reduction in fibrosis, a ∼40% reduction in apoptosis, and a ∼55% increase in angiogenesis, culminating in prominent cardiomyogenesis evidenced by abundant distribution of small myocytes and a ∼90% increase in wall thickening. These functional, histological, and molecular characterizations thus establish the utility of TLR3 engagement for enabling the low-dose MSC therapy that may be translated to more efficacious clinical applications.

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Introduction The presentation and optimal management of maternal focal atrial tachycardia (AT) during pregnancy are unknown. The objective of this study is to conduct a comprehensive summary of the existing evidence. Methods and Results A systematic review of all reported cases of maternal focal AT during pregnancy was performed. The primary search queried PubMed using the MeSH terms “supraventricular tachycardia” and “pregnancy.” A stepwise ancillary search included article bibliographies, citations listed by the Google internet search engine, and PubMed using the MeSH terms “atrial tachycardia” and “pregnancy.” In total, 28 citations that described 32 patients were retrieved. A case from our institution was added. Detailed information was available for 30 patients. Clinical characteristics at presentation included a mean ± standard deviation of 28.3 ± 5.7 years for maternal age and 24.6 ± 7.7 weeks for gestation age. Suspected tachycardia‐induced cardiomyopathy was present in 20 of 30 (67%) patients and left ventricular ejection fraction improved in 15 of 15 (100%) patients with follow‐up measurements. Medication failure was common. Focal AT resolved spontaneously after delivery in eight of nine (89%) patients treated with only medications. Automaticity was suggested by discrete electrograms at sites of origin and lack of reported inducibility and termination with programmed stimulation in all patients who underwent electrophysiology studies. There were nine cases of successful catheter ablation with zero fluoroscopy since 2010. Conclusions Automaticity is the dominant mechanism for patients with maternal focal AT during pregnancy. Catheter ablation with zero fluoroscopy is an emerging therapy for medically refractory cases.

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