Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT®) Mesenchymal Stromal Cell committee position statement on nomenclature.

The International Society for Cell & Gene Therapy (ISCT®) Mesenchymal Stromal Cell (ISCT MSC) committee offers a position statement to clarify the nomenclature of mesenchymal stromal cells (MSCs). The ISCT MSC committee continues to support the use of the acronym "MSCs" but recommends this be (i) supplemented by tissue-source origin of the cells, which would highlight tissue-specific properties; (ii) intended as MSCs unless rigorous evidence for stemness exists that can be supported by both in vitro and in vivo data; and (iii) associated with robust matrix of functional assays to demonstrate MSC properties, which are not generically defined but informed by the intended therapeutic mode of actions.

Achieving orphan designation for placental insufficiency: annual incidence estimations in Europe.

OBJECTIVE: To determine whether a novel therapy for placental insufficiency could achieve orphan drug status by estimating the annual incidence of placental insufficiency, defined as an estimated fetal weight below the 10th centile in the presence of abnormal umbilical artery Doppler velocimetry, per 10 000 European Union (EU) population as part of an application for European Medicines Agency (EMA) orphan designation. DESIGN: Incidence estimation based on literature review and published national and EU statistics. SETTING AND POPULATION: European Union. METHODS: Data were drawn from published literature, including national and international guidelines, international consensus statements, cohort studies and randomised controlled trials, and published national and EU statistics, including birth rates and stillbirth rates. Rare disease databases were also searched. RESULTS: The proportion of affected pregnancies was estimated as 3.17% (95% CI 2.93-3.43%), using a weighted average of the results from two cohort studies. Using birth rates from 2012 and adjusting for a pregnancy loss rate of 1/100 gave an estimated annual incidence of 3.33 per 10 000 EU population (95% CI 3.07-3.60 per 10 000 EU population). This fell below the EMA threshold of 5 per 10 000 EU population. CONCLUSIONS: Maternal vascular endothelial growth factor gene therapy for placental insufficiency was granted EMA orphan status in 2015 after we demonstrated that it is a rare, life-threatening or chronically debilitating and currently untreatable disease. Developers of other potential obstetric therapies should consider applying for orphan designation, which provides financial and regulatory benefits. TWEETABLE ABSTRACT: Placental insufficiency meets the European Medicines Agency requirements for orphan disease designation.

Preparation and characterization of non-viral gene delivery systems with pEGFP-C1 Plasmid DNA

ABSTRACT In recent years, non-viral delivery systems for plasmid DNA have become particularly important. They can overcome the disadvantages of viral systems such as insertional mutagenesis and unpredicted immunogenicity. Some additional advantages of non-viral gene delivery systems are; good stability, low cost, targetability, delivery of a high amount of genetic materials. The aim of the study was to develop novel non-viral nanosystems suitable for gene delivery. Two formulations were developed for this purpose: water-in-oil microemulsion (ME) and solid lipid nanoparticles (SLN). The microemulsion was composed of Peceol, Tween 80, Plurol oleique, ethanol and water. The SLN was consisting of Precirol, Esterquat-1 (EQ1), Tween 80, Lecithin, ethanol and water. Characterization studies were carried out by measuring particle size, zeta potential, viscosity and pH. TEM imaging was performed on SLN formulations. Protection against DNase I degradation was examined. Cytotoxicity and transfection efficacy of selected formulations were tested on L929 mouse fibroblast cells. Particle sizes of complexes were below 100 nm and with high positive zeta potential. TEM images revealed that SLNs are spherical. The SLN:DNA complexes have low toxicity and good transfection ability. All results showed that the developed SLN formulations can be considered as suitable non-viral gene delivery systems.

The advanced therapy classification procedure. Overview of experience gained so far.

The classification procedure, introduced by the European Regulation on advanced therapy medicinal products (ATMPs), has received a tremendous interest from companies, academic and public sponsors developing ATMPs. This procedure gives companies the opportunity to verify whether or not the product they are developing can be considered an ATMP and can therefore benefit from the new regulatory pathway introduced in the European Union for these types of medicinal products. This procedure is optional, free of charge and may take place at any stage of the development of an ATMP in advance of applying for a marketing authorisation. In case of doubt, briefing meetings organised by the European Medicines Agency Innovation Task Force may help preparing for an ATMP classification and are a starting point for the interactions between the Agency and the developers of ATMPs. This article reviews the advantages of the classification procedure for both the developers of ATMPs and the European regulatory network. Since the introduction of this procedure and up to 10 November 2010, the Committee for Advanced Therapies (CAT) has finalised 38 applications for classification.

[Gene therapy strategies for colorectal cancer]. / Gentherapeutische Strategien gegen das kolorektale Karzinom.

Current advances in CRC treatment have led to significant but slight improvements in patient survival with curative outcomes only seen in earlier stage cancers. Consequently, much effort is being put into developing completely novel therapies that fulfil a number of criteria including greater efficacy and fewer side effects. Many of these conditions are met by the wide range of gene therapy strategies currently in pre-clinical or clinical trial phases. Gene therapy approaches may be broadly broken down into three main areas: Following a few tragic events in the context of clinical gene therapy studies, safety is currently the prime concern. Further progress in the field is expected from the combination of the described approaches with conventional treatment modalities.

Gene therapy for the treatment of oral squamous cell carcinoma.

Despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with oral squamous cell carcinoma has not significantly improved over the past several decades. Treatment options for recurrent or refractory oral cancers are limited. Gene therapy for oral cancer is currently under investigation in clinical trials. The goal of cancer gene therapy is to introduce new genetic material into target cells without toxicity to non-target tissues. This review discusses the techniques used in cancer gene therapy for oral squamous cell carcinoma and summarizes the ongoing strategies that are being evaluated in clinical trials.

[Realities and hopes of gene therapy]. / Real'nosti i nadezhdy gennoi terapii.

The work represents an introduction article of editors of special issue of the magazine devoted to gene therapy and therapeutics. The main results of clinical gene therapy in the past decade are critically considered in connection with a changes of paradigms of the field. They are: 1) change of the main target of genetic therapy--correction of defects in chromosomes--onto expression and/or output of target genes for gene therapy; 2) transfer from gene transplantation to cell transplantation; 3) tendency for the use of safe/non-viral vectors instead of viral ones.; and 4) conflict of interests in gene therapy. Outlooks in the field are discussed.

Gene therapy--when a simple concept meets a complex reality. Review on gene therapy.

In theory, gene therapy is a simple concept which holds great promise as a cure for disease. In practice, however, considerable obstacles have to be overcome, including problems with safe and efficient gene delivery and stable gene expression. This review gives an overview on the history of gene therapy and analyses some of the problems that have so far prevented the establishment of a successful clinical protocol. The future prospects of gene therapy are discussed.

Molecular chemotherapy for breast cancer.

Gene therapy for breast cancer initially involves local or systemic delivery. Local delivery may be intrapleural or via direct injection to lesions. However, systemic delivery remains the greatest challenge with targeting, although methods using antibodies or growth factor receptor ligands have been demonstrated in preclinical models. This review focuses on the next step of using tissue-specific promoters such as Muc-1, CEA, PSA, HER-2, Myc, L-plastin and secretory leukoproteinase inhibitor promoters. All of these have demonstrated differential upregulation in breast cancer and additional specificity may be obtained by using physiological stimuli that are more frequently expressed in cancers, such as glucose regulated promoters and hypoxia response elements or radiation inducible elements. Amongst the later are the EGR-1, p21 and tissue type plaminogen activator promoters. Potential therapy genes include the prodrug activation system 5-fluorocytosine and other analogues of antimetabolites, but all of these need gap junctions to transfer the phosphorylated metabolites. Other approaches involving more freely diffusible products include cyclophosphamide, ifosfamide and thymidine phosphorylase to activate 5-deoxy-5-fluoruridine to fluorouracil. The bystander effect is important both for cell killing and for immunological and antivascular effects. Breast cancer is one type of tumour where a major clinical research effort is underway using local delivery methods. For prodrug activation systems, the use of human enzymes is desirable to prevent an immunological response that would eventually eliminate cells producing the prodrug activation system. The use of alkylating agents has an advantage over antimetabolites in that they are cytotoxic to cycling and noncycling cells, and the cytotoxic products can diffuse across cell membranes without the need for gap junctions. They also have a much steeper dose response curve than antimetabolites.

Possibilities of gene therapies for cancer.

Cancer is an acquired disease in which it is possible to identify a variety of abnormalities at a genetic level. This holds a promise that genetic manipulation of tumour cells will lead to novel therapies. As yet these approaches are constrained by available methods for obtaining gene transfer and subsequent genetic control. However, a number of strategies are already reaching the clinic, including attempts at immunotherapy, prodrug activation and improving host defence against conventional chemotherapy. Further clinical opportunities will occur with improved vector development.

Gene therapy for head and neck cancer.

BACKGROUND: Molecular or gene therapy involves the introduction of genetic material (DNA) into host cells to induce the expression of the therapeutic product of that gene. This ability to transfer genetic material provides a novel approach for the investigation and potential treatment of a variety of both inherited and acquired diseases. METHODS: This review summarizes the principles of molecular therapy and potential strategies for its use in the treatment of solid malignancies. Some molecular therapy strategies permanently integrate the gene into the targeted cells, whereas others induce only transient expression of a therapeutic gene product. Initial clinical studies in gene therapy are being closely regulated for public safety by both the National Institutes of Health Recombinant DNA Advisory Committee and the U.S. Food and Drug Administration. CONCLUSIONS: These studies will provide insight into further applications of gene therapy and novel molecular interventions that may alter our management of solid malignancies; they may also reveal mechanisms for preventing or reversing the carcinogenic process.