scholarly journals Treatment of Lymphedema with Cell-Based Therapies: A Systematic Review

2020 ◽  
Vol 3 ◽  
Author(s):  
Connor Drake ◽  
Lily Suh ◽  
Colby Neumann ◽  
Imran Khan ◽  
Mithun Sinha ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Animal Models ◽  
English Language ◽  
Human Subjects ◽  
Immunosuppressive Agents ◽  
Parasitic Infection ◽  
Cell Transplant ◽  
Compression Garments ◽  
In Vivo Models

Introduction  Lymphedema is a chronic condition that affects over 250 million people worldwide. It results from impaired lymphatic drainage, causing fluid and fat accumulation and eventually fibrosis of the affected limb. Lymphedema can be inherited (primary) or iatrogenic to surgery or parasitic infection (secondary). Breast cancer-related lymphedema is the most common etiology in the U.S. Current treatments have limited success and the disease mechanisms are not well understood. The purpose of this article is to review translational research into lymphedema therapies and its potential clinical impact.     Methods  A Pubmed search for novel treatment methods was performed with terms “lymphedema,” “cell therapy,” and “gene therapy.” Inclusion criteria were use of in vivo models, English language, and publication dates during the years 2000-2020.    Results  Secondary lymphedema is currently treated with compression garments and surgery; other approaches are being pursued. These include gene therapy (13 articles), stem cell transplant (16 articles), and immunosuppression (4 articles), which have all demonstrated considerable success in animal models of lymphedema. Growth factors such as VEGF-C are administered through adenoviral vectors and resolve limb swelling by inducing lymphangiogenesis. Stem cells derived from bone marrow or adipose tissue repair lymphatic damage directly by acquiring lymphatic characteristics or indirectly through paracrine signaling to surrounding cells. Immunosuppressive agents reduce inflammation and block antilymphangiogenic factors. Although these mechanisms have been studied in animals, only six human small studies were found, providing limited evidence.     Conclusion  Despite success in animal models, treatment in human subjects has been sparse. This limited translational feasibility is because of inadequate animal models, safety concerns, and lack of understanding about lymphedema pathophysiology. Although progress in lymphedema research has been made, further inquiry into its mechanism is needed in order to develop more effective and targeted therapies. 

Genetic Engineering of AAV Capsid Gene for Gene Therapy Application

2020 ◽  
Vol 20 (5) ◽  
pp. 321-332
Author(s):  
Yunbo Liu ◽  
Xu Zhang ◽  
Lin Yang
Keyword(s):  
Gene Therapy ◽  
Neutralizing Antibodies ◽  
Human Subjects ◽  
Genetic Diseases ◽  
Capsid Gene ◽  
Human Populations ◽  
Stable Gene ◽  
Efficient Gene ◽  
Gene Therapy Application

Adeno-associated virus (AAV) is a promising vector for in vivo gene therapy because of its excellent safety profile and ability to mediate stable gene expression in human subjects. However, there are still numerous challenges that need to be resolved before this gene delivery vehicle is used in clinical applications, such as the inability of AAV to effectively target specific tissues, preexisting neutralizing antibodies in human populations, and a limited AAV packaging capacity. Over the past two decades, much genetic modification work has been performed with the AAV capsid gene, resulting in a large number of variants with modified characteristics, rendering AAV a versatile vector for more efficient gene therapy applications for different genetic diseases.

scholarly journals Neuromuscular Development and Disease: Learning From in vitro and in vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Zachary Fralish ◽  
Ethan M. Lotz ◽  
Taylor Chavez ◽  
Alastair Khodabukus ◽  
Nenad Bursac
Keyword(s):  
Skeletal Muscle ◽  
Cell Culture ◽  
Animal Models ◽  
Schwann Cells ◽  
Motor Neurons ◽  
Small Animal ◽  
In Vivo Models ◽  
Small Animal Models

The neuromuscular junction (NMJ) is a specialized cholinergic synaptic interface between a motor neuron and a skeletal muscle fiber that translates presynaptic electrical impulses into motor function. NMJ formation and maintenance require tightly regulated signaling and cellular communication among motor neurons, myogenic cells, and Schwann cells. Neuromuscular diseases (NMDs) can result in loss of NMJ function and motor input leading to paralysis or even death. Although small animal models have been instrumental in advancing our understanding of the NMJ structure and function, the complexities of studying this multi-tissue system in vivo and poor clinical outcomes of candidate therapies developed in small animal models has driven the need for in vitro models of functional human NMJ to complement animal studies. In this review, we discuss prevailing models of NMDs and highlight the current progress and ongoing challenges in developing human iPSC-derived (hiPSC) 3D cell culture models of functional NMJs. We first review in vivo development of motor neurons, skeletal muscle, Schwann cells, and the NMJ alongside current methods for directing the differentiation of relevant cell types from hiPSCs. We further compare the efficacy of modeling NMDs in animals and human cell culture systems in the context of five NMDs: amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular dystrophy, myotonic dystrophy, and Pompe disease. Finally, we discuss further work necessary for hiPSC-derived NMJ models to function as effective personalized NMD platforms.

A Novel Peptide Aldehyde with Activity against Human Cytomegalovirus in Two Different in Vivo Models

2000 ◽  
Vol 11 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Olaf Weber ◽  
Jürgen Reefschläger ◽  
Helga Rübsamen-Waigmann ◽  
Siegfried Raddatz ◽  
Matthias Hesseling ◽  
...  
Keyword(s):  
Animal Models ◽  
Antiviral Activity ◽  
Clinical Isolate ◽  
Human Cytomegalovirus ◽  
Murine Cytomegalovirus ◽  
Human Tissues ◽  
In Vivo Models ◽  
Peptide Aldehydes

Novel peptide aldehydes (PAs) were identified as potent inhibitors of human cytomegalovirus (HCMV) in vitro. Although these compounds were highly effective against HCMV, they did not exhibit any activity against murine cytomegalovirus (MCMV). The purpose of this study was to test the antiviral activity of PA 8 as a representative of this novel class of inhibitors against HCMV in vivo. Because of the strict species specificity of HCMV we had to use two artificial animal models. In the first model, HCMV-infected human cells were entrapped into agarose plugs and transplanted into mice. In the second model, SCID mice were transplanted with human tissues that were subsequently infected with a clinical isolate of HCMV. In these two models the antiviral activity of PA 8 was clearly demonstrated, ganciclovir only being slightly superior in its in vivo antiviral activity.

Efficacy, Mechanism, and Safety of Herbal Medicine for Respiratory Disease Induced by Particulate Matter: a Protocol for a Scoping Review

2021 ◽  
Author(s):  
Jungtae Leem ◽  
Yohwan Kim ◽  
Kwan-Il Kim
Keyword(s):  
Particulate Matter ◽  
Animal Models ◽  
Respiratory Disease ◽  
Scoping Review ◽  
Respiratory Diseases ◽  
English Language ◽  
Herbal Medicines ◽  
Cochrane Central Register

Abstract Background: Particulate matter (PM) is an important environmental risk factor in the initiation and exacerbation of respiratory disease. Various herbal medicines have exhibited a reduction in symptoms of respiratory diseases induced by PM in animal models; however, their efficacy, mechanism, and safety have not been reviewed. This review will evaluate the efficacy, safety, and mechanism of action of herbal medicines in respiratory diseases caused by PM. Methods:We will follow the scoping review framework developed by Arksey and O’Malley. MEDLINE (via PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials will be searched for relevant English-language publications, and only peer-reviewed, controlled comparative in-vivo/in-vitro studies examining the effects of herbs in animal models of respiratory disease induced by PM will be included. The basic characteristics, research method, possible mechanism, and results will be extracted. The primary outcome will be pulmonary function; secondary outcomes will be inflammatory markers, reactive oxygen species, histology and mechanisms, and adverse events. Two researchers will independently perform the study selection, data extraction, and quality assessment. RevMan software (version 5.3) will be used for the quantitative data synthesis. When appropriate, data will be pooled for meta-analysis using fixed or random effects models; otherwise, evidence will be summarized qualitatively. Ethics and Dissemination: Ethical approval is not required because individual patient data will not be included. The findings will be disseminated through peer-reviewed publications or conference presentations.Registration number: This review protocol has been registered with the Open Science Framework on February 12, 2021 (https://osf.io/s7uvk/)

scholarly journals Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

2019 ◽  
Vol 5 (3) ◽  
pp. eaaw0873 ◽  
Author(s):  
Hao Zhang ◽  
Philipp Gutruf ◽  
Kathleen Meacham ◽  
Michael C. Montana ◽  
Xingyue Zhao ◽  
...  
Keyword(s):  
Animal Models ◽  
Tissue Oxygenation ◽  
Human Subjects ◽  
Brain Regions ◽  
Disease States ◽  
Data Output ◽  
Subdermal Implants ◽  
Underlying Mechanisms ◽  
Tissue Oximetry

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.

scholarly journals In Vivo Models for Cholangiocarcinoma—What Can We Learn for Human Disease?

2020 ◽  
Vol 21 (14) ◽  
pp. 4993 ◽  
Author(s):  
Raphael Mohr ◽  
Burcin Özdirik ◽  
Jana Knorr ◽  
Alexander Wree ◽  
Münevver Demir ◽  
...  
Keyword(s):  
Animal Models ◽  
Human Disease ◽  
Liver Tumors ◽  
Tumor Biology ◽  
Genetic Alterations ◽  
In Vivo Models ◽  
Primary Liver Tumors ◽  
Stromal Microenvironment

Cholangiocarcinoma (CCA) comprises a heterogeneous group of primary liver tumors. They emerge from different hepatic (progenitor) cell populations, typically via sporadic mutations. Chronic biliary inflammation, as seen in primary sclerosing cholangitis (PSC), may trigger CCA development. Although several efforts were made in the last decade to better understand the complex processes of biliary carcinogenesis, it was only recently that new therapeutic advances have been achieved. Animal models are a crucial bridge between in vitro findings on molecular or genetic alterations, pathophysiological understanding, and new therapeutic strategies for the clinic. Nevertheless, it is inherently difficult to recapitulate simultaneously the stromal microenvironment (e.g., immune-competent cells, cholestasis, inflammation, PSC-like changes, fibrosis) and the tumor biology (e.g., mutational burden, local growth, and metastatic spread) in an animal model, so that it would reflect the full clinical reality of CCA. In this review, we highlight available data on animal models for CCA. We discuss if and how these models reflect human disease and whether they can serve as a tool for understanding the pathogenesis, or for predicting a treatment response in patients. In addition, open issues for future developments will be discussed.

scholarly journals Animal Models of Zika Virus Infection during Pregnancy

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 598 ◽  
Author(s):  
Elizabeth Caine ◽  
Brett Jagger ◽  
Michael Diamond
Keyword(s):  
Animal Models ◽  
Virus Infection ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Congenital Abnormalities ◽  
Tissue Tropism ◽  
Zikv Infection ◽  
In Vivo Models ◽  
Sexually Transmitted

Zika virus (ZIKV) emerged suddenly in the Americas in 2015 and was associated with a widespread outbreak of microcephaly and other severe congenital abnormalities in infants born to mothers infected during pregnancy. Vertical transmission of ZIKV in humans was confirmed when viral RNA was detected in fetal and placental tissues, and this outcome has been recapitulated experimentally in animals. Unlike other flaviviruses, ZIKV is both arthropod- and sexually-transmitted, and has a broad tissue tropism in humans, including multiple tissues of the reproductive tract. The threats posed by ZIKV have prompted the development of multiple in vivo models to better understand the pathogenesis of ZIKV, particularly during pregnancy. Here, we review the progress on animal models of ZIKV infection during pregnancy. These studies have generated a foundation of insights into the biology of ZIKV, and provide a means for evaluating vaccines and therapeutics.

scholarly journals In Vivo Models Used for Evaluation of Potential Antigastroduodenal Ulcer Agents

Ulcers ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Michael Buenor Adinortey ◽  
Charles Ansah ◽  
Isaac Galyuon ◽  
Alexander Nyarko
Keyword(s):  
Peptic Ulcer ◽  
Animal Models ◽  
Gastrointestinal Diseases ◽  
Experimental Models ◽  
Lower Side ◽  
In Vivo Models ◽  
Biochemical Basis ◽  
Lead Compounds ◽  
Antiulcer Drugs

Peptic ulcer is among the most serious gastrointestinal diseases in the world. Several orthodox drugs are employed for the treatment of the disease. Although these drugs are effective, they produce many adverse effects thus limiting their use. In recent years, there has been a growing interest in alternative therapies, especially those from plants due to their perceived relative lower side effects, ease of accessibility, and affordability. Plant medicines with ethnomedicinal use in peptic ulcer management need to be screened for their effectiveness and possible isolation of lead compounds. This requires use of appropriate animal models of various ulcers. The limited number of antiulcer models for drug development against gastric and duodenal ulcer studies has hindered the progress of targeted therapy in this field. It is, therefore, necessary to review the literature on experimental models used to screen agents with potential antigastroduodenal ulcer activity and explain their biochemical basis in order to facilitate their use in the development of new preventive and curative antiulcer drugs. Clinical trials can then be carried out on agents/drugs that show promise. In this paper, current in vivo animal models of ulcers and the pathophysiological mechanisms underlying their induction, their limitations, as well as the challenges associated with their use have been discussed.

scholarly journals Adenovirus-Mediated Expression of a Ribozyme to c-mybmRNA Inhibits Smooth Muscle Cell Proliferation and Neointima Formation In Vivo

1999 ◽  
Vol 73 (9) ◽  
pp. 7745-7751 ◽  
Author(s):  
Dennis G. Macejak ◽  
Hua Lin ◽  
Saiphone Webb ◽  
Jennifer Chase ◽  
Kristi Jensen ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Smooth Muscle ◽  
Animal Models ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Recombinant Adenovirus ◽  
Neointima Formation ◽  
Inhibition Of Proliferation

ABSTRACT Smooth muscle cell (SMC) proliferation is an important component of restenosis in response to injury after balloon angioplasty. Inhibition of proliferation in vivo can limit neointima hyperplasia in animal models of restenosis. Ribozymes against c-myb mRNA have been shown to be effective inhibitors of SMC proliferation in vitro. The effectiveness of adenovirus as a gene therapy vector in animal models of restenosis is well documented. In order to test the utility of ribozymes to inhibit SMC proliferation by a gene therapy approach, recombinant adenovirus expressing ribozymes against c-mybmRNA was generated and tested both in vitro and in vivo. This adenovirus ribozyme vector is shown to inhibit SMC proliferation in culture and neointima formation in a rat carotid artery balloon injury model of restenosis.

Sign in / Sign up

Export Citation Format

Share Document