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Gelati M.,Laboratorio Cellule Staminali | Profico D.,Laboratorio Cellule Staminali | Projetti-Pensi M.,Laboratorio Cellule Staminali | Muzi G.,Laboratorio Cellule Staminali | And 3 more authors.
Methods in Molecular Biology | Year: 2013

NSCs have been demonstrated to be very useful in grafts into the mammalian central nervous system to investigate the exploitation of NSC for the therapy of neurodegenerative disorders in animal models of neurodegenerative diseases. To push cell therapy in CNS on stage of clinical application, it is necessary to establish a continuous and standardized, clinical grade (i.e., produced following the good manufacturing practice guidelines) human neural stem cell lines. In this chapter, we illustrate some of the protocols routinely used into our GMP cell bank for the production of "clinical grade" human neural stem cell lines. © Springer Science+Business Media New York 2013.

Mazzini L.,Maggiore della Carita University Hospital | Vescovi A.,IRCCS Casa Sollievo della Sofferenza | Vescovi A.,Laboratorio Cellule Staminali | Cantello R.,University of Piemonte Orientale | And 3 more authors.
Expert Opinion on Biological Therapy | Year: 2016

Introduction: Despite knowledge on the molecular basis of amyotrophic lateral sclerosis (ALS) having quickly progressed over the last few years, such discoveries have not yet translated into new therapeutics. With the advancement of stem cell technologies there is hope for stem cell therapeutics as novel treatments for ALS.Areas covered: We discuss in detail the therapeutic potential of different types of stem cells in preclinical and clinical works. Moreover, we address many open questions in clinical translation.Expert opinion: SC therapy is a potentially promising new treatment for ALS and the need to better understand how to develop cell-based experimental treatments, and how to implement them in clinical trials, becomes more pressing. Mesenchymal stem cells and neural fetal stem cells have emerged as safe and potentially effective cell types, but there is a need to carry out appropriately designed experimental studies to verify their long-term safety and possibly efficacy. Moreover, the cost-benefit analysis of the results must take into account the quality of life of the patients as a major end point. It is our opinion that a multicenter international clinical program aime d at fine-tuning and coordinating transplantation procedures and protocols is mandatory. © 2016 Taylor & Francis.

Ferrari D.,University of Milan Bicocca | Zalfa C.,University of Milan Bicocca | Nodari L.R.,University of Milan Bicocca | Gelati M.,Casa Sollievo della Sofferenza | And 6 more authors.
Cellular and Molecular Life Sciences | Year: 2012

Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T-IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications. © 2011 Springer Basel AG.

Mazzini L.,University of Piemonte Orientale | Gelati M.,Laboratorio Cellule Staminali | Profico D.C.,Laboratorio Cellule Staminali | Sgaravizzi G.,Laboratorio Cellule Staminali | And 40 more authors.
Journal of Translational Medicine | Year: 2015

Background: We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanità and the competent Ethics Committees and was monitored by an external Safety Board. Methods: Six non-ambulatory patients were treated. Three of them received 3 unilateral hNSCs microinjections into the lumbar cord tract, while the remaining ones received bilateral (n = 3 + 3) microinjections. None manifested severe adverse events related to the treatment, even though nearly 5 times more cells were injected in the patients receiving bilateral implants and a much milder immune-suppression regimen was used as compared to previous trials. Results: No increase of disease progression due to the treatment was observed for up to18 months after surgery. Rather, two patients showed a transitory improvement of the subscore ambulation on the ALS-FRS-R scale (from 1 to 2). A third patient showed improvement of the MRC score for tibialis anterior, which persisted for as long as 7 months. The latter and two additional patients refused PEG and invasive ventilation and died 8 months after surgery due to the progression of respiratory failure. The autopsies confirmed that this was related to the evolution of the disease. Conclusions: We describe a safe cell therapy approach that will allow for the treatment of larger pools of patients for later-phase ALS clinical trials, while warranting good reproducibility. These can now be carried out under more standardized conditions, based on a more homogenous repertoire of clinical grade hNSCs. The use of brain tissue from natural miscarriages eliminates the ethical concerns that may arise from the use of fetal material. © 2015 Mazzini et al.

Meregalli M.,Laboratorio Cellule Staminali | Farini A.,Laboratorio Cellule Staminali | Belicchi M.,Laboratorio Cellule Staminali | Parolini D.,Laboratorio Cellule Staminali | And 4 more authors.
FEBS Journal | Year: 2013

Muscular dystrophies are heritable and heterogeneous neuromuscular disorders characterized by the primary wasting of skeletal muscle, usually caused by mutations in the proteins forming the link between the cytoskeleton and the basal lamina. As a result of mutations in the dystrophin gene, Duchenne muscular dystrophy patients suffer from progressive muscle atrophy and an exhaustion of muscular regenerative capacity. No efficient therapies are available. The evidence that adult stem cells were capable of participating in the regeneration of more than their resident organ led to the development of potential stem cell treatments for degenerative disorder. In the present review, we describe the different types of myogenic stem cells and their possible use for the progression of cell therapy in Duchenne muscular dystrophy. Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy and unfortunately no effective therapy is available at present. As stem cells received much attention for their potential use in cell-based therapies for human diseases, herein we described multiple types of resident and circulating myogenic stem cells, their characterization and their possible use to treat muscular dystrophies. © 2012 The Authors Journal compilation © 2012 FEBS.

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