Theme A: Modeling and simulation in biomedical research. Results and future works

This paper presents the activity of the theme A “Modeling and simulation in biomedical research” within the GdR STIC Santé. This group has organized four scientific meetings and has managed one action, together with the theme B “Biomedical Signal and Image Processing”, during the period 2011–2012. The meetings have focused on modeling of the cardiorespiratory control, on the modeling and physiopathology of cardiovascular system and on Complex Systems in Biology and Medicine (co-organized with the GDR “Dynamique et Contrôle des Systèmes Complexes” – DYCOEC). The fourth one represents the official start of the “VPH-France” network that has been labeled by the Réseau National de Systèmes Complexes (RNSC). The SIGnal-processing and Modeling methods to Undertake Neonatal care during Development (SIGMUND) action has concerned seven hospitals and five CIC-IT (Clinical Technological Innovation Center) and has brought to the development of a regional project (Care-Premi) including three of the seven hospitals. The future works will focus: on strengthening the interactions with other topics of this GDR and with other GDRs, on application of modeling to solve real clinical heath problems, on the better acceptation of modeling by the industrial community.     

Theme G: eHealth. Results and future works

In this paper, we briefly describe the eHealth theme of GdR STIC-Santé we created in January 2011, then we summarize the main contributions to the promotion, development, organization and diffusion of research, innovation, education and training initiatives in the field of eHealth we provided in 2011–2012, and we finally draw some perspectives for future works for the coming years.     

Cardiac rehabilitation. Current status and future directions.

Comprehensive cardiac rehabilitation is more than exercise training for patients with coronary artery disease and now includes all aspects of secondary prevention. Exercise training is individually prescribed based on clinical status and therapeutic goals. Smoking cessation and abstinence and the treatment of hypercholesterolemia are integral to the rehabilitation process. Education and counseling are important adjuncts to treatment, especially soon after a coronary event. Vocational rehabilitation can be included simply and effectively in the rehabilitation process. Efficient and cost-effective cardiac rehabilitation is tailored to a patient''s medical condition, risk factor evaluation, and vocational status. The future of cardiac rehabilitation will be linked to the success of training nonphysician health professionals to provide preventive services.     

Tropomyosin Dephosphorylation Results in Compensated Cardiac Hypertrophy

Phosphorylation of tropomyosin (Tm) has been shown to vary in mouse models of cardiac hypertrophy. Little is known about the in vivo role of Tm phosphorylation. This study examines the consequences of Tm dephosphorylation in the murine heart. Transgenic (TG) mice were generated with cardiac specific expression of α-Tm with serine 283, the phosphorylation site of Tm, mutated to alanine. Echocardiographic analysis and cardiomyocyte cross-sectional area measurements show that α-Tm S283A TG mice exhibit a hypertrophic phenotype at basal levels. Interestingly, there are no alterations in cardiac function, myofilament calcium (Ca²⁺) sensitivity, cooperativity, or response to β-adrenergic stimulus. Studies of Ca²⁺ handling proteins show significant increases in sarcoplasmic reticulum ATPase (SERCA2a) protein expression and an increase in phospholamban phosphorylation at serine 16, similar to hearts under exercise training. Compared with controls, the decrease in phosphorylation of α-Tm results in greater functional defects in TG animals stressed by transaortic constriction to induce pressure overload-hypertrophy. This is the first study to investigate the in vivo role of Tm dephosphorylation under both normal and cardiac stress conditions, documenting a role for Tm dephosphorylation in the maintenance of a compensated or physiological phenotype. Collectively, these results suggest that modification of the Tm phosphorylation status in the heart, depending upon the cardiac state/condition, may modulate the development of cardiac hypertrophy.     

Cardiac stem cells: Current knowledge and future prospects

Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole organs.Since the inception of the field several decades ago,regenerative medicine therapies,namely stem cells,have received significant attention in preclinical studies and clinical trials.Apart from their known potential for differentiation into the various body cells,stem cells enhance the organ's intrinsic regenerative capacity by altering its environment,whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of regeneration.Recently,research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells(CSCs/CPCs).The global burden of cardiovascular diseases’morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic strategy.This review will discuss the nature of each of the CSCs/CPCs,their environment,their interplay with other cells,and their metabolism.In addition,important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other cells.Moreover,the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac regeneration.Finally,the novel role of nanotechnology in cardiac regeneration will be explored.     

Historical progress and the future of human cell culture research.

Progress in human cell culture research is discussed based primarily on our hematopoietic cell culture studies. The article includes a historical background of Burkitt lymphoma cell lines, discovery of EBV, normal B-lymphoblastoid cell lines with EBV, a variety of leukemia, lymphoma, and myeloma cell lines, clinical and theoretical contributions made by studies of T-cell leukemia cell lines, the discovery and clinical relevance of HTLV, HIV and HBLV, early attempts at adoptive immunotherapy of patients with cancer, and the future of human cell culture research. Despite the fact that current cell culture methods permit maintenance of only limited cell types of both normal and malignant origins, biotechnological advances such as hybridoma and recombinant DNA technologies should continue to provide unlimited research opportunities in all fields.     

Cardiac matrix: A clue for future therapy

Cardiac muscle is unique because it contracts ceaselessly throughout the life and is highly resistant to fatigue. The marvelous nature of the cardiac muscle is attributed to its matrix that maintains structural and functional integrity and provides ambient micro-environment required for mechanical, cellular and molecular activities in the heart. Cardiac matrix dictates the endothelium myocyte (EM) coupling and contractility of cardiomyocytes. The matrix metalloproteinases (MMPs) and their tissue inhibitor of metalloproteinases (TIMPs) regulate matrix degradation that determines cardiac fibrosis and myocardial performance. We have shown that MMP-9 regulates differential expression of micro RNAs (miRNAs), calcium cycling and contractility of cardiomyocytes. The differential expression of miRNAs is associated with angiogenesis, hypertrophy and fibrosis in the heart. MMP-9, which is involved in the degradation of cardiac matrix and induction of fibrosis, is also implicated in inhibition of survival and differentiation of cardiac stem cells (CSC). Cardiac matrix is distinct because it renders mechanical properties and provides a framework essential for differentiation of cardiac progenitor cells (CPC) into specific lineage. Cardiac matrix regulates myocyte contractility by EM coupling and calcium transients and also directs miRNAs required for precise regulation of continuous and synchronized beating of cardiomyocytes that is indispensible for survival. Alteration in the matrix homeostasis due to induction of MMPs, altered expression of specific miRNAs or impaired signaling for contractility of cardiomyocytes leads to catastrophic effects. This review describes the mechanisms by which cardiac matrix regulates myocardial performance and suggests future directions for the development of treatment strategies in cardiovascular diseases.