Translational Research RSS feed: Articles in Press. Translational Research delivers original investigations in the broad fields of laboratory, clinical, and public health research. Interdisciplinary and cross-disciplinary in scope, it keeps readers up-to-date on significant biomedical research from all subspecialties of medicine. Aiming to expedite the translation of scientific discovery into new or improved standards of care, it promotes a wide-ranging exchange between basic, preclinical, clinical, epidemiologic, and health outcomes research. It encourages submission of studies describing preclinical research with potential for application to human disease, and studies describing research obtained from preliminary human experimentation with potential to refine the understanding of biological principles underpinning human disease. Also encouraged are studies describing public health research with potential for application to the clinic, disease prevention, or healthcare policy.http://www.translationalres.com//inpress?rss=yesElsevier Inc.en © 2010 Mosby, Inc. All rights reserved. Translational Research1931-52442010-07-23 © 2010 Mosby, Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.translationalres.com/article/PIIS1931524410001507/abstract?rss=yes“Regenerative medicine” hopefully will provide novel therapies for diseases that remain without effective therapy. This development is also true for most neurodegenerative disorders including Alzheimer’s disease, Huntington’s disease, or Parkinson’s disease. Transplantation of new neurons to the brain has been performed in Parkinson’s disease and in Huntington’s disease. The restoration of dopaminergic neurons in patients with Parkinson’s disease via implantation of embryonic midbrain tissue was taken from animal experiments to clinical applications, showing a limited efficacy. Clinical trials in patients with Huntington’s disease using fetal striatal tissue currently are underway. Today, it seems possible to generate functional dopaminergic or striatal neurons form a variety of stem cells including embryonic or neural stem cells as well as induced pluripotent stem cells. First clinical trials using neural stem cell or embryonic-stem-cell-derived tissue are approved or already underway. Such cells allow for extensive in vitro and in vivo testing as well as “good manufacturing production,” reducing the risks in clinical application.Translation of stem cell therapy for neurological diseases - Uncorrected ProofSigrid C. Schwarz, Johannes Schwarz10.1016/j.trsl.2010.07.002Translational Research (2010)2010-07-23Translational Research2010-07-23REVIEW ARTICLEhttp://www.translationalres.com/article/PIIS1931524410001234/abstract?rss=yesCardiovascular disease is the leading cause of death and disability in the Western world. In addition to the advancement of current therapeutic approaches to reduce the associated morbidity and mortality, regenerative medicine and cell-based therapy have been areas of continuous investigation. Circulating and bone-marrow-derived stem or endothelial progenitor cells are an attractive source for regenerative therapy in the cardiovascular field. In this review, we highlight the advantages and limitations of this approach with a focus on key observations from animal studies and clinical trials.Bone marrow and circulating stem/progenitor cells for regenerative cardiovascular therapy - Uncorrected ProofMohamad Amer Alaiti, Masakazu Ishikawa, Marco A. Costa10.1016/j.trsl.2010.06.008Translational Research (2010)2010-07-20Translational Research2010-07-20REVIEW ARTICLEhttp://www.translationalres.com/article/PIIS1931524410001246/abstract?rss=yesDuring the past 30 years, hundreds of pharmacological agents have been developed for the treatment of heart failure; yet few of them ultimately have been tested in patients. Such a disconcerting debacle has spurred the search for nonpharmacological therapies, including those based on cardiac delivery of transgenes and stem cells. Cardiac gene therapy preceded stem cell therapy by approximately 10 years; however, both of them already have known an initial phase of enormous enthusiasm followed by moderate-to-strong skepticism, not necessarily justified. The aim of the present review is to discuss succinctly some key aspects of these 2 biological therapies and to argue that after a phase of disillusionment, gene therapy for the failing heart likely will have the chance to regain the stage. In fact, discoveries in stem cell biology might revitalize gene therapy, and vice versa, gene therapy might potentiate synergistically the regenerative capacity of stem cells.New therapies for the failing heart: trans-genes versus trans-cells - Uncorrected ProofVincenzo Lionetti, Fabio A. Recchia10.1016/j.trsl.2010.06.009Translational Research (2010)2010-07-16Translational Research2010-07-16REVIEW ARTICLEhttp://www.translationalres.com/article/PIIS1931524410001209/abstract?rss=yesApproximately 23.6 million people or 7.8% of the population in the United States are afflicted with diabetes. Another 57 million have prediabetes—people who are prone to develop frank diabetes in the coming years. The total costs of diagnosed diabetes were estimated to be $174 billion in 2007, which included $116 billion for direct medical costs and $58 billion for indirect costs (resulting from disability, work loss, and premature mortality). Type 2 diabetes accounts for some 90% of patients, whereas type 1a (autoimmune) diabetes accounts for most other diabetic patients. Individuals with type 1 diabetes have absolute insulin deficiency, whereas those with the type 2 disease, relative insulin deficiency, are usually in the presence of insulin resistance. Insulin injections are the standard therapy for type 1 diabetes. Unfortunately, insulin secretion is exquisitely sensitive to the minute-to-minute changes in blood glucose, and glycemia stimulated insulin secretion (GSIS) cannot be mimicked by exogenous insulin injections. Pancreas transplantation is an effective mode of therapy, but it is associated with considerable operative morbidity and mortality. Although the initial success with the Edmonton protocol popularized pancreatic islet transplantation as a form of treatment, this option has had some severe limitations. Donor availability limits the number of transplants that can be done; the need for lifetime immunosuppression is another problem. Moreover, although short-term experiments indicate that in good centers, up to ∼80% of transplant recipients can become free of insulin injections shortly after the procedure, long-term follow up indicates that most are back on insulin again within 5 years. These difficulties have prompted research into the development of innovative methods to generate new β cells in the body.Stem cell approaches for the treatment of type 1 diabetes mellitus - Uncorrected ProofRyan T. Wagner, Jennifer Lewis, Austin Cooney, Lawrence Chan10.1016/j.trsl.2010.06.005Translational Research (2010)2010-07-12Translational Research2010-07-12REVIEW ARTICLEhttp://www.translationalres.com/article/PIIS1931524410001192/abstract?rss=yesNonalcoholic fatty liver disease (NAFLD), which is linked strictly to the epidemics of obesity and the metabolic syndrome, represents the leading cause of liver disease in Western countries. The prevalence of NAFLD is 24% to 30% of the general population, and it is still increasing progressively, especially in the pediatric age. In particular, NAFLD affects 3% to 10% of children and adolescents, but this figure increases up to approximately 80% in obese individuals. Insulin resistance related to central obesity, altered lifestyle, and the metabolic syndrome is a pivotal factor in NAFLD pathophysiology and is entangled deeply with the progression of liver disease. Hyperalimentation associated with inadequate physical activity leading to a progressive increase of body mass and visceral adiposity predisposes to pediatric NAFLD. This incidence is becoming more and more diffuse with the daily consumption of fast foods and soft drinks, associated with inactive leisure activities, such as watching television or playing video games.Serum hyaluronic acid for the screening of progressive nonalcoholic steatohepatitis in children: a promising approach - Uncorrected ProofLuca Valenti, Paola Dongiovanni10.1016/j.trsl.2010.06.004Translational Research (2010)2010-07-09Translational Research2010-07-09COMMENTARYhttp://www.translationalres.com/article/PIIS1931524410001222/abstract?rss=yesCell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases, including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models.Stem cells and cell therapy approaches in lung biology and diseases - Uncorrected ProofViranuj Sueblinvong, Daniel J. Weiss10.1016/j.trsl.2010.06.007Translational Research (2010)2010-07-08Translational Research2010-07-08REVIEW ARTICLEhttp://www.translationalres.com/article/PIIS1931524410001180/abstract?rss=yesThe intestinal epithelium contains a rapidly proliferating and perpetually differentiating epithelium. The principal functional unit of the small intestine is the crypt–villus axis. The stem cells located in the crypts of Lieberkühn give rise to proliferating progenitor or transit amplifying cells that differentiate into the 4 major epithelial cell types. The study of adult gastrointestinal tract stem cells has progressed rapidly with the recent discovery of several putative stem cell markers. Substantial evidence suggests 2 populations of stem cells: long-term quiescent (reserved) and actively cycling (primed) stem cells. These cells are in adjoining locations and are presumably maintained by the secretion of specific proteins generated in a unique microenvironment or stem cell niche surrounding each population. The relationship between these 2 populations, as well as the cellular sources and composition of the surrounding environment, remains to be defined, and it is an active area of research. In this review, we will outline progress in identifying stem cells and in defining epithelial–mesenchymal interactions in the crypt. We will summarize early advances using stem cells for therapy of gastrointestinal disorders.Intestinal stem cells and epithelial–mesenchymal interactions in the crypt and stem cell niche - Uncorrected ProofAnisa Shaker, Deborah C. Rubin10.1016/j.trsl.2010.06.003Translational Research (2010)2010-07-05Translational Research2010-07-05REVIEW ARTICLEShttp://www.translationalres.com/article/PIIS1931524410001167/abstract?rss=yesThe immune system responds to tuberculosis (TB) infection by forming granulomas. However, subsequent immune-mediated destruction of lung tissue is a cause of significant morbidity and contributes to disease transmission. Lactoferrin, an iron-binding glycoprotein, has demonstrated immunomodulatory properties that decrease tissue destruction and promote TH1 immune responses, both of which are essential for controlling TB infection. The cord factor trehalose 6,6'-dimycolate (TDM) model of granuloma formation mimics many aspects of TB infection with a similar histopathology accompanied by proinflammatory cytokine production. C57BL/6 mice were injected intravenously with TDM. A subset of mice was given 1 mg of bovine lactoferrin 24 h post-TDM challenge. Lung tissue was analyzed for histological response and for the production of proinflammatory mediators. C57BL/6 mice demonstrated a granuloma formation that correlated with an increased production of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α,) IL-12p40, interferon-gamma (IFN-γ), and IL-10 protein. Mice treated with lactoferrin postchallenge had significantly fewer and smaller granulomas compared with those given TDM alone. Proinflammatory and TH1 cytokines essential to the control of mycobacterial infections, such as TNF-α and IFN-γ, were not significantly different in mice treated with lactoferrin. Furthermore, the anti-inflammatory cytokines IL-10 and transforming growth factor-β were increased. A potential mechanism for decreased tissue damage observed in the lactoferrin-treated mice is proposed. Because of its influence to modulate immune responses, lactoferrin may be a useful adjunct in the treatment of granulomatous inflammation occurring during mycobacterial infection.Lactoferrin modulation of mycobacterial cord factor trehalose 6-6'-dimycolate induced granulomatous response - Uncorrected ProofKerry J. Welsh, Shen-An Hwang, Robert L. Hunter, Marian L. Kruzel, Jeffrey K. Actor10.1016/j.trsl.2010.06.001Translational Research (2010)2010-07-01Translational Research2010-07-01ORIGINAL ARTICLEhttp://www.translationalres.com/article/PIIS1931524410001015/abstract?rss=yesNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents, and it may progress to liver fibrosis and cirrhosis. Liver biopsy, which is the recognized gold standard for the diagnosis of hepatic fibrosis, is invasive. Thus, there has been increasing interest in the development of noninvasive markers. Hyaluronic acid (HA) has been shown to be a good marker of liver fibrosis in adults. In the current study, we evaluated the association of HA with liver fibrosis in 100 consecutive children with biopsy-proven NAFLD. In all, 65% of the children had liver fibrosis. Using proportional-odds ordinal logistic regression, we found that values of HA ≥ 1200 ng/mL made the absence of fibrosis (F0) unlikely (7%, 95% confidence interval [CI]: 1% to 14%), whereas values of HA ≥ 2100 ng/mL made F2, F3, or F4 fibrosis likely (89%, 95% CI: 75% to 100%). Our study shows that HA is a predictor of fibrosis in children with NAFLD followed at a tertiary care center. Additional studies are needed to test whether HA can be employed to predict liver fibrosis in pediatric populations with similar and lower prevalence of liver fibrosis.Hyaluronic acid predicts hepatic fibrosis in children with nonalcoholic fatty liver disease - Uncorrected ProofValerio Nobili, Anna Alisi, Giuliano Torre, Rita De Vito, Andrea Pietrobattista, Giuseppe Morino, Jean Deville De Goyet, Giorgio Bedogni, Massimo Pinzani10.1016/j.trsl.2010.05.008Translational Research (2010)2010-06-23Translational Research2010-06-23ORIGINAL ARTICLEShttp://www.translationalres.com/article/PIIS1931524409002412/abstract?rss=yesHypersensitivity pneumonitis (HP) is an inflammatory lung disease caused by repeated inhalation of aerosolized antigens. With chronic exposure to an inhaled antigen, patients are at risk of developing irreversible pulmonary fibrosis and increased morbidity and mortality. Although αβ T cells have been shown to be important in the pathogenesis of HP, γδ T cells are also found and may protect against lung damage and fibrosis caused by chronic exposure to an inhaled pathogen. Th1 cytokines have been implicated in the pathogenesis of HP; yet patients with HP still develop pulmonary fibrosis suggesting that other T-cell cytokines may be involved. Th17 cytokines are a novel group of effector molecules expressed by various T lymphocytes, including γδ T cells. Th17-expressing γδ T cells are important for mucosal immunity against invading microbial pathogens and other inhaled antigens. An increased understanding of γδ T cells that express Th17 cytokines in HP may lead to the development of novel therapeutic and clinical strategies that prevent fibrotic lung disease in patients with HP.γδ T cells and Th17 cytokines in hypersensitivity pneumonitis and lung fibrosis - Uncorrected ProofPhilip L. Simonian, Christina L. Roark, Willi K. Born, Rebecca L. O'Brien, Andrew P. Fontenot10.1016/j.trsl.2009.07.011Translational Research (2009)2009-08-24Translational Research2009-08-24REVIEW ARTICLE