Metalloproteinase alterations in the bone marrow of ALS patients.
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.
Bossolasco
Patrizia
P
Fondazione Matarelli, Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica, Università degli Studi di Milano, Via Vanvitelli, 32-20129, Milan, Italy. patrizia_bossolasco@yahoo.it
Cova
Lidia
L
Calzarossa
Cinzia
C
Servida
Federica
F
Mencacci
Niccolò Emanuele
NE
Onida
Francesco
F
Polli
Elio
E
Lambertenghi Deliliers
Giorgio
G
Silani
Vincenzo
V
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D001853:Bone Marrow / Q000201:enzymology*; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D008875:Middle Aged; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D024141:Collagen Type IV; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases