Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-04-25

AUTHORS

Cristina Zalfa, Laura Rota Nodari, Elena Vacchi, Maurizio Gelati, Daniela Profico, Marina Boido, Elena Binda, Lidia De Filippis, Massimiliano Copetti, Valentina Garlatti, Paola Daniele, Jessica Rosati, Alessandro De Luca, Francesca Pinos, Laura Cajola, Alberto Visioli, Letizia Mazzini, Alessandro Vercelli, Maria Svelto, Angelo Luigi Vescovi, Daniela Ferrari

ABSTRACT

Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3–L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3–L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS. More... »

PAGES

345

Journal

TITLE

Cell Death & Disease

ISSUE

5

VOLUME

10

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41419-019-1582-5

DOI

http://dx.doi.org/10.1038/s41419-019-1582-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113707788

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/31024007


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