Cardano M.,University of Milan |
Diaferia G.R.,Integrated Systems Engineering |
Cattaneo M.,Institute for Genetic and Biomedical Research |
Dessi S.S.,Integrated Systems Engineering |
And 7 more authors.
Journal of Biological Chemistry | Year: 2011
Murine SEL-1L (mSEL-1L) is a key component of the endoplasmic reticulum-associated degradation pathway. It is essential during development as revealed by the multi-organ dysfunction and in uterus lethality occurring in homozygous mSEL-1L-deficient mice. Here we show that mSEL-1L is highly expressed in pluripotent embryonic stem cells and multipotent neural stem cells (NSCs) but silenced in all mature neural derivatives (i.e. astrocytes, oligodendrocytes, and neurons) by mmumiR-183. NSCs derived from homozygous mSEL-1L-deficient embryos (mSEL-1L-/- NSCs) fail to proliferate in vitro, show a drastic reduction of the Notch effector HES-5, and reveal a significant down-modulation of the early neural progenitor markers PAX-6 and OLIG-2, when compared with the wild type (mSEL-1L+/+ NSCs) counterpart. Furthermore, these cells are almost completely deprived of the neural marker Nestin, display a significant decrease of SOX-2 expression, and rapidly undergo premature astrocytic commitment and apoptosis. The data suggest severe self-renewal defects occurring in these cells probably mediated by misregulation of the Notch signaling. The results reported here denote mSEL-1L as a primitive marker with a possible involvement in the regulation of neural progenitor stemness maintenance and lineage determination. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Gaipa G.,Laboratorio Interdipartimentale Of Terapia Cellulare Stefano Verri |
Gaipa G.,University of Milan Bicocca |
Tilenni M.,Centro Cardiologico Monzino IRCCS |
Straino S.,Dell |
And 13 more authors.
Journal of Cellular and Molecular Medicine | Year: 2010
The aim of the present study was to develop and validate a good manufacturing practice (GMP) compliant procedure for the preparation of bone marrow (BM) derived CD133 + cells for cardiovascular repair. Starting from available laboratory protocols to purify CD133 + cells from human cord blood, we implemented these procedures in a GMP facility and applied quality control conditions defining purity, microbiological safety and vitality of CD133 + cells. Validation of CD133 + cells isolation and release process were performed according to a two-step experimental program comprising release quality checking (step 1) as well as 'proofs of principle' of their phenotypic integrity and biological function (step 2). This testing program was accomplished using in vitro culture assays and in vivo testing in an immunosuppressed mouse model of hindlimb ischemia. These criteria and procedures were successfully applied to GMP production of CD133 + cells from the BM for an ongoing clinical trial of autologous stem cells administration into patients with ischemic cardiomyopathy. Our results show that GMP implementation of currently available protocols for CD133 + cells selection is feasible and reproducible, and enables the production of cells having a full biological potential according to the most recent quality requirements by European Regulatory Agencies. © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Gasmelseed N.,University of Gezira |
Elsir A.A.,University of Gezira |
DeBlasio P.,BioRep SrL |
Biunno I.,CNR Institute of Biomedical Technologies
Science of the Total Environment | Year: 2012
Quality-assessed biomedical samples are essential for academia- and industry driven research on human diseases. The etiologies and the molecular genetic factors relevant in African diseases, including both infections and complex degenerative diseases as well as cancer, need to be studied using well annotated and well-preserved biosamples acquired from native African ethnic groups and compare the results with non-African populations and/or with Afro-Americans. However, a number of difficulties negatively impact on the possibility to obtain clinically annotated biological samples in most Sub-Saharan African countries. This is mainly due to major organizational problems, lack of clinical centres that can dedicate resources to research, as well as lack of facilities in which biomaterials can be properly processed and safely stored. Harmonization of biosample acquisition, storage phenotyping schemes and biocomputer infrastructures are the principal objectives of biological resource centers (BRCs). BRCs comprise biobanks of different formats (collection of blood, DNA, tissues, etc., annotated with medical, environmental, life-style and follow up data) a fundamental tool for molecular epidemiological studies aiming to increase excellence and efficacy of biomedical results, drug development and public health. BRCs provide large and highly controlled biomolecular resources necessary to meet the "omics" scientific platforms. Sudan may be a candidate nation to host such infrastructure, in view of its strategic geographical position and the already existing simple biobanking experiences connected with research groups in Central Sudan. Here, we describe the potential role of biobanks in African genetic studies aiming to dissect the eziopathogenesis of complex diseases in relation to environmental and life-style factors. © 2010 Elsevier B.V.
Diaferia G.R.,Integrated Systems Engineering S.r.l. |
Biunno I.,Integrated Systems Engineering S.r.l. |
Biunno I.,CNR Institute of Neuroscience |
Deblasio P.,Integrated Systems Engineering S.r.l. |
Deblasio P.,BioRep S.r.l.
Biopreservation and Biobanking | Year: 2011
The validity of results from biomarker studies using archived specimens depends on the integrity of the specimens and the manner in which they are collected, processed, and stored. The management of a huge amount of biomaterial generated from research studies and clinical trials is becoming a very demanding task and many organizations are facing the choice between in-house storage and processing and outsourcing some activities. Storage and logistic functions are the prime targets for outsourcing, because to sustain these critical assets organizations must have the expertise, the dedicated qualified personnel, the proper quality control programs, and available resources to fulfill the mandatory requirements to maintain the integrity of the samples. External biobanks are dedicated and certified infrastructures (ISO, GMP, etc.) that apply efficient logistic and shipping activities, use validated standard operating procedures, install appropriate monitoring back-up systems, and, most of all, have room for expansion. Thus, the choice between in-house biobanking and outsourcing cannot be exclusively based on a financial decision; it must also consider (i) type of collection/project, (ii) logistic complexity (number and locations of collection sites), (iii) safety requirements, (iv) functional expertise, and (v) business priorities. © Copyright 2011, Mary Ann Liebert, Inc.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-1.4-6 | Award Amount: 15.84M | Year: 2008
The NEuroStemCell consortium will foster collaboration between leading European experimental and clinical researchers in order to maximise the prospects for successful clinical trials of stem cell therapy for Parkinsons (PD) and Huntingtons (HD) Disease. The activities will be driven by a Clinical WorkPackage (WP), which will set the requirements, and monitor and guide advances in development of the most promising cells. The goal is to compare different stem cell sources with respect to their capcity to generate mesencephalic Dopaminergic and striatal GABAergic neurons suitable for neuronal cell replacement. The major sources will be neuralised Embryonic Stem (ES) cells, adherent Neural Stem (NS) cell lines and short term expanded Ventral Midbrain neural stem cells/progenitors grown as Neurospheres (VMN). Two exploratory WPs will use extrinsic cues to specify neuronal differentiation and compare rigorously the different human stem cell lines and their progeny in giving rise to authentic neurons. WP3 will integrate long-term assessements of functional (motor and cognitive) recovery in appropriate animal models of PD and HD, and WP4 will exploit non-invasive in vivo imaging to evaluate the survival, composition, integration and functional impact of the donor cells in host brain. These two WPs will also provide the elements necessary to standardise the extent of recovery as a function of cell replacement and integration. In WP5, three SMEs will generate the technologies for manufacturing and scale-up of safe, fully traceable, efficacious and banked stocks of cells ready for clinical use. Regulatory and ethical requirements will be considered in the Clinical WP which also incorporates training. Building on the successful experience of the FPVI EuroStemCell project, NEuroStemCell will provide a focal point for European researchers engaged in the translational aspects of stem cell-based strategies to develop cures for PD and HD