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Armirotti A.,Advanced Biotechnology Center | Damonte G.,University of Genoa
Proteomics | Year: 2010

Over the last years, top-down (TD) MS has gained a remarkable space in proteomics, rapidly trespassing the limit between a promising approach and a solid, established technique. Several research groups worldwide have implemented TD analysis in their routine work on proteomics, deriving structural information on proteins with the level of accuracy that is impossible to achieve with classical bottom-up approaches. Complete maps of PTMs and assessment of single aminoacid polymorphisms are only a few of the results that can be obtained with this technique. Despite some existing technical and economical limitations, TD analysis is at present the most powerful instrument for MS-based proteomics and its implementation in routine workflow is a rapidly approaching turning point in proteomics. In this review article, the state-of-the-art of TD approach is described along with its major advantages and drawbacks and the most recent trends in TD analysis are discussed. References for all the covered topics are reported in the text, with the aim to support both newcomers and mass spectrometrists already introduced to TD proteomics. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Uccelli A.,University of Genoa | Uccelli A.,Advanced Biotechnology Center | Benvenuto F.,University of Genoa | Laroni A.,University of Genoa | Giunti D.,University of Genoa
Best Practice and Research: Clinical Haematology | Year: 2011

Bone marrow (BM) derived mesenchymal stem cells (MSC) differentiate into cells of the mesodermal lineage but also, under certain experimental circumstances, into cells of the neuronal and glial lineage. Their therapeutic translation has been significantly boosted by the demonstration that MSC display significant also anti-proliferative, anti-inflammatory and anti-apoptotic features. These properties have been exploited in the effective treatment of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis where the inhibition of the autoimmune response resulted in a significant neuroprotection. A significant rescue of neural cells has been achieved also when MSC were administered in experimental brain ischemia and in animals undergoing brain or spinal cord injury. In these experimental conditions BM-MSC therapeutic effects are likely to depend on paracrine mechanisms mediated by the release of growth factors, anti-apoptotic molecules and anti-inflammatory cytokines creating a favorable environment for the regeneration of neurons, remyelination and improvement of cerebral flow. For potential clinical application BM-MSC offer significant practical advantages over other types of stem cells since they can be obtained from the adult BM and can be easily cultured and expanded in vitro under GMP conditions displaying a very low risk of malignant transformation. This review discusses the targets and mechanisms of BM-MSC mediated neuroprotection. © 2011 Published by Elsevier Ltd. Source

Uccelli A.,Ophthalmology and Genetics | Uccelli A.,University of Genoa | Uccelli A.,Advanced Biotechnology Center | Mancardi G.,Ophthalmology and Genetics | Mancardi G.,University of Genoa
Current Opinion in Neurology | Year: 2010

PURPOSE OF REVIEW: The recent advances in our understanding of stem cell biology, the availability of innovative techniques that allow large-scale acquisition of stem cells, and the increasing pressure from the multiple sclerosis (MS) patient community seeking tissue repair strategies have launched stem cell treatments as one of the most exciting and difficult challenges in the MS field. Here, we provide an overview of the current status of stem cell research in MS focusing on secured actuality, reasonable hopes and unrealistic myths. RECENT FINDINGS: Results obtained from small clinical studies with transplantation of autologous hematopoietic stem cells have demonstrated that this procedure is feasible and possibly effective in severe forms of MS but tackles exclusively inflammation without affecting tissue regeneration. Results from preclinical studies with other adult stem cells such as mesenchymal stem cells and neural precursor cells have shown that they may be a powerful tool to regulate pathogenic immune response and foster tissue repair through bystander mechanisms with limited cell replacement. However, the clinical translation of these results still requires careful evaluation. CONCLUSION: Current experimental evidence suggests that the sound clinical exploitation of stem cells for MS may lead to novel strategies aimed at blocking uncontrolled inflammation, protecting neurons and promoting remyelination but not at restoring the chronically deranged neural network responsible for irreversible disability typical of the late phase of MS. © 2010 Lippincott Williams & Wilkins. Source

Uccelli A.,University of Genoa | Uccelli A.,Advanced Biotechnology Center | Laroni A.,University of Genoa | Freedman M.S.,Ottawa Hospital Research Institute
Multiple Sclerosis Journal | Year: 2013

The unmet need for therapies capable of repairing the central nervous system (CNS) damage occurring in many diseases including multiple sclerosis (MS) has sparked the interest of the neurological community for stem cell-based therapies. An exhaustive amount of preclinical data has shown that the intravenous administration of mesenchymal stem cells (MSC), a subset of progenitor cells isolated from many mesodermal tissues, effectively ameliorates experimental autoimmune encephalomyelitis (EAE), a model of MS, through the release of anti-inflammatory and neuroprotective molecules. Based on these results, several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair as realized clinically, with functional recovery, or visualized by magnetic resonance imaging (MRI). © The Author(s) 2012. Source

Uccelli A.,University of Genoa | Uccelli A.,Advanced Biotechnology Center | Prockop D.J.,Texas A&M University
Current Opinion in Immunology | Year: 2010

The adult stem/progenitor cells from bone marrow and other tissues referred to as mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) display a significant therapeutic plasticity as reflected by their ability to enhance tissue repair and influence the immune response both in vitro and in vivo. In this review we will focus on the paradigmatic preclinical experience achieved testing MSCs in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. We will emphasize how the paradigm changed over time from the original prediction that MSCs would enhance tissue repair through their transdifferentiation into somatic cells to the current paradigm that they can produce therapeutic benefits without engraftment into the injured tissues. The data will be reviewed in terms of the potentials of MSCs for therapy of autoimmune diseases. © 2010 Elsevier Ltd. Source

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