Repeated Application of Autologous Bone Marrow-Derived Lineage-Negative Stem/Progenitor Cells—Focus on Immunological Pathways in Patients with ALS
2020
Bartłomiej Baumert | Anna Sobuś | Monika Gołąb-Janowska | Edyta Paczkowska | Karolina Łuczkowska | Dorota Rogińska | Alicja Zawiślak | Sławomir Milczarek | Bogumiła Osękowska | Wioletta Pawlukowska | Agnieszka Meller | Karolina Machowska-Sempruch | Agnieszka Wełnicka | Krzysztof Safranow | Przemysław Nowacki | Bogusław Machaliński
Therapeutic interventions in amyotrophic lateral sclerosis (ALS) are still far from satisfying. Immune modulating procedures raise hopes for slowing the disease progression. Stem cell therapies are believed to possess the ability to regulate innate and adaptive immune response and inflammation processes. Hence, three intrathecal administrations of autologous bone marrow-derived lineage-negative (Lin<sup>–</sup>) cells were performed every six weeks in 40 sporadic ALS patients. The concentrations of inflammatory-related proteins and expression profiles of selected miRNA in the cerebrospinal fluid (CSF) and plasma at different timepoints post-transplantation were quantified by multiplex Luminex and qRT-PCR. The global gene expression in nucleated blood cells was assessed using the gene microarray technique. According to the ALS Functional Rating Scale (FRSr), the study population was divided into responders (group I, n = 17) and non-responders (group II, n = 23). A thorough analysis of the pro-inflammatory expression profiles, regulated miRNA pathways, and global gene expression profiles at the RNA level revealed the local and systemic effects of Lin<sup>–</sup> cell therapy on the immune system of patients with ALS. The autologous application of Lin<sup>–</sup> cells in CSF modulates immune processes and might prevent the progression of neurodegeneration. However, further in-depth studies are necessary to confirm the findings, and prolonged intervention is needed to maintain therapeutic effects.
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