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Obesity and its co-morbidities including type 2 diabetes are increasing at epidemic rates in the U.S. and worldwide. Brown adipose tissue (BAT) is a potential therapeutic to combat obesity and type 2 diabetes. Increasing BAT mass by transplantation improves metabolic health in rodents, but its clinical translation remains a challenge. Here, we investigated if transplantation of 2-4 million differentiated brown pre-adipocytes from mouse BAT stromal fraction (SVF) or human pluripotent stem cells (hPSCs) could improve metabolic health. Transplantation of differentiated brown pre-adipocytes, termed "committed pre-adipocytes" from BAT SVF from mice or derived from hPSCs improves glucose homeostasis and insulin sensitivity in recipient mice under conditions of diet-induced obesity, and this improvement is mediated through the collaborative actions of the liver transcriptome, tissue AKT signaling, and FGF21. These data demonstrate that transplantation of a small number of brown adipocytes has significant long-term translational and therapeutic potential to improve glucose metabolism.
RESUMO
Human pluripotent stem cells (hPSCs) can be used as a renewable source of endothelial cells for treating cardiovascular disease and other ischemic conditions. Here, we present the derivation and characterization of a panel of distinct clonal embryonic endothelial progenitor cells (eEPCs) lines that were differentiated from human embryonic stem cells (hESCs). The hESC line, ESI-017, was first partially differentiated to produce candidate cultures from which eEPCs were cloned. Endothelial cell identity was assessed by transcriptomic analysis, cell surface marker expression, immunocytochemical marker analysis, and functional analysis of cells and exosomes using vascular network forming assays. The transcriptome of the eEPC lines was compared to various adult endothelial lines as well as various non-endothelial cells including both adult and embryonic origins. This resulted in a variety of distinct cell lines with functional properties of endothelial cells and strong transcriptomic similarity to adult endothelial primary cell lines. The eEPC lines, however, were distinguished from adult endothelium by their novel pattern of embryonic gene expression. We demonstrated eEPC line scalability of up to 80 population doublings (pd) and stable long-term expansion of over 50 pd with stable angiogenic properties at late passage. Taken together, these data support the finding that hESC-derived clonal eEPC lines are a potential source of scalable therapeutic cells and cell products for treating cardiovascular disease. These eEPC lines offer a highly promising resource for the development of further preclinical studies aimed at therapeutic interventions.
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Growing evidence supports the antagonistic pleiotropy theory of mammalian aging. Accordingly, changes in gene expression following the pluripotency transition, and subsequent transitions such as the embryonic-fetal transition, while providing tumor suppressive and antiviral survival benefits also result in a loss of regenerative potential leading to age-related fibrosis and degenerative diseases. However, reprogramming somatic cells to pluripotency demonstrates the possibility of restoring telomerase and embryonic regeneration pathways and thus reversing the age-related decline in regenerative capacity. A unified model of aging and loss of regenerative potential is emerging that may ultimately be translated into new therapeutic approaches for establishing induced tissue regeneration and modulation of the embryo-onco phenotype of cancer.
Assuntos
Envelhecimento , Modelos Biológicos , Regeneração , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapiaAssuntos
Imunoterapia/métodos , Oncologia/métodos , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T , Linfócitos T , Pessoal de Saúde/economia , Pessoal de Saúde/tendências , Humanos , Imunoterapia/economia , Imunoterapia/tendências , Oncologia/economia , Oncologia/tendências , Neoplasias/economia , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologiaAssuntos
Indústria Farmacêutica/tendências , Imunoterapia Adotiva/tendências , Receptores de Antígenos/uso terapêutico , Linfócitos T , Transferência de Tecnologia , Composição de Medicamentos , Indústria Farmacêutica/economia , Humanos , Imunoterapia Adotiva/economia , Receptores de Antígenos/químicaAssuntos
Aminobutiratos/economia , Terapia Baseada em Transplante de Células e Tecidos , Terapia Genética , Gastos em Saúde , Tetrazóis/economia , Compostos de Bifenilo , Terapia Baseada em Transplante de Células e Tecidos/economia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Combinação de Medicamentos , Europa (Continente) , Terapia Genética/economia , Terapia Genética/métodos , Humanos , Estados Unidos , ValsartanaAssuntos
Medicina Regenerativa/tendências , Mecanismo de Reembolso/tendências , Terapia Baseada em Transplante de Células e Tecidos/economia , Terapia Baseada em Transplante de Células e Tecidos/estatística & dados numéricos , Terapia Baseada em Transplante de Células e Tecidos/tendências , Custos e Análise de Custo , Humanos , Medicina Regenerativa/economia , Engenharia Tecidual/economia , Engenharia Tecidual/estatística & dados numéricos , Engenharia Tecidual/tendênciasAssuntos
Perfilação da Expressão Gênica/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Medicina de Precisão/economia , Medicina de Precisão/métodos , Biomarcadores/análise , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/economia , Medicamentos Biossimilares/farmacologia , HumanosRESUMO
Three key areas in diagnostics will drive the convergence of diagnostic and communication technologies: point-of-care testing, micro-electromechanical systems and biomarker discovery. In addition, the communications revolution means that increasing numbers of people will be able to send data from their home to their doctor using the Internet. Also, the widespread availability of broadband opens up the possibly of realtime videoconferencing with clinicians. It is already possible for patients at home to monitor simple variables, such as heart rate and blood pressure, and send their results using communication technologies to their doctors, who can promptly review the information to diagnose problems. As diagnostic and communication technologies converge, it will be feasible for patients to transmit more complex health-care data periodically to their doctor, who will be able to identify problems early on and thus modify disease management to prevent exacerbations of patients' medical conditions. This will allow improved patient care in a wide range of health-care situations, from acute medical conditions to chronic disease.
Assuntos
Biomarcadores , Comunicação , Sistemas Microeletromecânicos/instrumentação , Sistemas Automatizados de Assistência Junto ao Leito , Telemedicina/métodos , Humanos , Sistemas Automatizados de Assistência Junto ao Leito/organização & administração , Sistemas Automatizados de Assistência Junto ao Leito/tendências , Telemedicina/tendênciasRESUMO
The cost of monoclonal antibody therapies for cancer is soaring out of control. Healthcare payers and patients are increasingly struggling to meet the high costs, which can be up to US$100,000 a year. A number of methods have been proposed to control these costs-government price controls on cancer drugs, biosimilars and novel drug pricing strategies. This article discusses what the impact of these strategies would be in terms of their ability to reduce costs and their effect on innovative cancer drug discovery.
Assuntos
Antineoplásicos/economia , Custos de Medicamentos , Descoberta de Drogas , Neoplasias/tratamento farmacológico , Neoplasias/economia , Antineoplásicos/uso terapêutico , Controle de Custos , Custos e Análise de Custo/economia , HumanosRESUMO
Leading pharmaceutical companies are increasingly making biotech acquisitions to help them refill their pipelines, but what makes a good acquisition target and what will be the impact of the present financial crisis on deals.
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Biotecnologia/tendências , Descoberta de Drogas/tendências , Indústria Farmacêutica/economia , Biotecnologia/economia , Descoberta de Drogas/economiaRESUMO
Drug discovery is hard, and is becoming progressively harder, with the passage of time! No other field has to handle such an interplay of scientific, fiscal and political factors. The rewards are, nonetheless, worth it: people now live healthier and longer lives than at any point of time in the past. Times are, however, hard for pharmaceutical companies: research and development (R&D) costs are spiralling out of control. New drug approvals, on the other hand, have hit a record low; and the situation is expected to worsen, now that the FDA seems to be exhibiting stricter drug approval standards. Other issues also exacerbate circumstances: huge numbers of blockbuster medicines, which drugmakers rely on to generate their incomes, are coming off patent, and generic competition is intensifying. Both public and investor confidence in the industry have fallen drastically owing to rising drug prices, product safety concerns and late-stage clinical trial failures. This article discusses the key issues that pharmaceutical companies face and in particular the implications they have for the R&D process. I finish by suggesting how drugmakers should change their R&D strategies to succeed.