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Metalloproteinase alterations in the bone marrow of ALS patients

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, nowadays considered as suitable candidate for autologous stem therapy with bone marrow (BM). A careful characterization of BM stem cell (SC) compartment is mandatory before its extensive application to clinic. Indeed, widespread systemic involvement has been recently advocated given that non-neuronal neighboring cells actively influence the pathological neuronal loss. We therefore investigated BM samples from 21 ALS patients and reported normal hematopoietic biological properties while an atypical behavior and impaired SC capabilities affected only the mesenchymal compartment. Moreover, by quantitative real-time approach, we observed altered Collagen IV and Metalloproteinase-9 levels in patients’ derived mesenchymal stem cells (MSCs). Widespread metalloproteinase (MMPs) and their tissue inhibitor (TIMPs) alterations were established by multiplex ELISA analysis, demonstrating diffuse enzymatic variations in MSC compartment. Since MMPs act as fundamental effectors of extra-cellular matrix remodeling and stem cell mobilization, their modifications in ALS may influence reparative mechanisms effective in counteracting the pathology. In conclusion, ALS is further confirmed to be a systemic disease, not restricted to the nervous system, but affecting also the BM stromal compartment, even in sporadic cases. Therefore, therapeutic implantation of autologous BM derived SC in ALS patients needs to be carefully reevaluated.

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Acknowledgment

We dedicate this work to the loving memory of Professor Davide Soligo.

Author contributions

Patrizia Bossolasco and Lidia Cova contributed in conception and design, experiments, data analysis and interpretation, and writing the manuscript. Calzarossa Cinzia performed experiments and analyzes data. Federica Servida performed experiments. Mencacci Niccolò Emanuele contributed in the collection and critical classification of clinical data. Francesco Onida, Elio Polli, and Lambertenghi Deliliers Giorgio contributed to the final approval of manuscript. Vincenzo Silani contributed in the probation of patients and final approval of manuscript.

Competing interests statement

The authors declare that they have no competing financial interests.

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Authors and Affiliations

  1. Fondazione Matarelli, Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica, Università degli Studi di Milano, Via Vanvitelli, 32-20129, Milan, Italy

    Patrizia Bossolasco, Federica Servida, Francesco Onida & Elio Polli

  2. Department of Neurology and Laboratory of Neuroscience, Centro “Dino Ferrari”, Università degli Studi di Milano-IRCCS Istituto Auxologico Italiano, Milan, Italy

    Lidia Cova, Cinzia Calzarossa, Niccolò Emanuele Mencacci & Vincenzo Silani

  3. U.O. Ematologia 1-CTMO, Fondazione Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy

    Francesco Onida & Giorgio Lambertenghi Deliliers

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  1. Patrizia Bossolasco
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  2. Lidia Cova
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  3. Cinzia Calzarossa
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  4. Federica Servida
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  5. Niccolò Emanuele Mencacci
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  6. Francesco Onida
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  7. Elio Polli
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  8. Giorgio Lambertenghi Deliliers
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  9. Vincenzo Silani
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Correspondence to Patrizia Bossolasco.

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Patrizia Bossolasco and Lidia Cova contributed equally to the work.

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Bossolasco, P., Cova, L., Calzarossa, C. et al. Metalloproteinase alterations in the bone marrow of ALS patients. J Mol Med 88, 553–564 (2010). https://doi.org/10.1007/s00109-009-0584-7

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  • DOI: https://doi.org/10.1007/s00109-009-0584-7

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