We provide a patent‐eligibility analysis of methods used in induced pluripotent stem cell (iPSC) theranostics, which links the discovery–diagnostics–therapeutics pipeline across a single platform. ...This article investigates recent statutory and judicial exclusions from patentability in the United States, compares them with exclusions in Europe, and highlights potential shortfalls of patent applications claiming the triad of disease modeling, cellular diagnostics, and personalized therapeutics with potential implications for patient care.
Clinical Pharmacology & Therapeutics (2013); 93 4, 318–320. doi:10.1038/clpt.2013.11
Recent trends indicate that patients with nonischemic dilated cardiomyopathy represent the largest subpopulation of heart failure patients with a significant need for alternative treatment ...modalities. Similar to patients with ischemic cardiomyopathy, patients with nonischemic dilated cardiomyopathy have been found to have myocardial regions with flow abnormalities, which may represent targets for neoangiogenic therapies. CD34+ stem cells might contribute to the formation of new blood vessels from existing vascular structures in ischemic tissues by the direct incorporation of injected cells into the newly developing vasculature or by the production and secretion of angiogenic cytokines. This review summarizes the long‐term clinical effects and potential underlying mechanisms of CD34+ cell therapy in patients with nonischemic dilated cardiomyopathy.
Clinical Pharmacology & Therapeutics (2013); 94 4, 452–458. doi:10.1038/clpt.2013.134
Abstract Background The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest ...has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. Methods and results A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. Conclusions The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.
Cell-based therapy has emerged as a promising strategy for the treatment of patients with heart failure. Increasing evidence supports the hypothesis that paracrine mechanisms mediated by soluble ...factors released by the cells play a predominate role in reparative processes. The aim of our study was to analyze which cytokines are released by CD34+ enriched cell products intended for autologous transendocardial CD34+ cell transplantation in patients with cardiomyopathy.
The peripheral blood CD34+ cells from 12 patients were mobilized with granulocyte colony-stimulating factor, collected via apheresis and enriched by immunoselection.
In CD34+ enriched cell population, hematopoietic, but not mesenchymal or endothelial, progenitors were detected. Except for angiopoietin-1, other measured cytokines (FGF1, FGF2, VEGF, PDGF, IL-6, HGH, SDF-1α/CXCL12, NRG1) were not released by CD34+ cells. The average concentration of angiopoietin-1 released by 5×106 CD34+ cells grown in neutral DMEM medium was 213.6±130.0pg/mL (range: 74–448pg/mL). Angiopoietin-1 secretion correlated well with CD34+ cell's capacity for generating colonies derived from hematopoietic progenitors (Pearson's correlation=0.964; P<0.001).
Our study presents angiopoietin-1 as an interesting candidate and suggests future studies to explore how its release by CD34+ cells might impact the success of autologous CD34+ cell transplantation.
La thérapie cellulaire est devenue une stratégie prometteuse pour le traitement des patients souffrant d’insuffisance cardiaque. De plus en plus de preuves corroborent l’hypothèse selon laquelle les mécanismes paracrines véhiculés par les facteurs solubles libérés par les cellules jouent un rôle prédominant dans les processus de réparation. Le but de notre étude était d’analyser les cytokines libérées par les produits cellulaires enrichis en CD34 + destinés à la transplantation autologue de cellules CD34 + transendocardiques chez des patients atteints de cardiomyopathie.
Les cellules CD34 + du sang périphérique de 12 patients ont été mobilisées avec le facteur de stimulation des colonies de granulocytes, collectées via une aphérèse et enrichies par immunosélection.
Dans la population cellulaire enrichie en CD34 +, des progéniteurs hématopoïétiques, mais non-mésenchymateux ou endothéliaux, ont été détectés. À l’exception de l’angiopoïétine-1, d’autres cytokines mesurées (FGF1, FGF2, VEGF, PDGF, IL-6, HGH, SDF-1α / CXCL12, NRG1) n’ont pas été libérées par les cellules CD34 +. La concentration moyenne d’angiopoïétine-1 libérée par 5×106 cellules CD34 + cultivées dans un milieu DMEM neutre était de 213,6±130,0 pg/mL (écart: 74–448 pg/mL). La sécrétion d’angiopoïétine-1 était bien corrélée avec la capacité des cellules CD34 + à générer des colonies dérivées de progéniteurs hématopoïétiques (corrélation de Pearson=0,964 ; p<0,001).
Notre étude présente l’angiopoïétine-1 comme un candidat intéressant et propose des études futures pour explorer l’impact de sa libération par les cellules CD34 + sur le succès de la transplantation de cellules CD34 + autologues.
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