Metalloproteinase alterations in the bone marrow of ALS patients

Patrizia Bossolasco, Lidia Cova, Cinzia Calzarossa, Federica Servida, Niccolò Emanuele Mencacci, Francesco Onida, Elio Polli, Giorgio Lambertenghi Deliliers, Vincenzo Silani

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)553-564
Number of pages12
JournalJournal of Molecular Medicine
Volume88
Issue number6
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Amyotrophic lateral sclerosis
  • Bone marrow
  • Cell therapy
  • Collagen
  • Mesenchymal stem cells
  • Metalloproteinases

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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