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Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases.

ABSTRACT: Neurological disorders include a wide spectrum of clinical conditions affecting the central and peripheral nervous systems. For these conditions, which affect hundreds of millions of people worldwide, generally limited or no treatments are available, and cell-based therapies have been intensively investigated in preclinical and clinical studies. Among the available cell types, mesenchymal stem/stromal cells (MSCs) have been widely studied but as yet no cell-based treatment exists for neurological disease. We review current knowledge of the therapeutic potential of MSC-based therapies for neurological diseases, as well as possible mechanisms of action that may be explored to hasten the development of new and effective treatments. We also discuss the challenges for culture conditions, quality control, and the development of potency tests, aiming to generate more efficient cell therapy products for neurological disorders.

SUBMITTER: Soares MBP

PROVIDER: S-EPMC9244712 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases.

Soares Milena B P MBP Gonçalves Renata G J RGJ Vasques Juliana F JF da Silva-Junior Almir J AJ Gubert Fernanda F Santos Girlaine Café GC de Santana Thaís Alves TA Almeida Sampaio Gabriela Louise GL Silva Daniela Nascimento DN Dominici Massimo M Mendez-Otero Rosalia R

Frontiers in molecular neuroscience 20220616

Neurological disorders include a wide spectrum of clinical conditions affecting the central and peripheral nervous systems. For these conditions, which affect hundreds of millions of people worldwide, generally limited or no treatments are available, and cell-based therapies have been intensively investigated in preclinical and clinical studies. Among the available cell types, mesenchymal stem/stromal cells (MSCs) have been widely studied but as yet no cell-based treatment exists for neurologica ...[more]

PMID: 35782379

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Project description:Skin disease may be related with immunological disorders, external aggressions, or genetic conditions. Injuries or cutaneous diseases such as wounds, burns, psoriasis, and scleroderma among others are common pathologies in dermatology, and in some cases, conventional treatments are ineffective. In recent years, advanced therapies using human mesenchymal stem cells (hMSCs) from different sources has emerged as a promising strategy for the treatment of many pathologies. Due to their properties; regenerative, immunomodulatory and differentiation capacities, they could be applied for the treatment of cutaneous diseases. In this review, a total of thirteen types of hMSCs used as advanced therapy have been analyzed, considering the last 5 years (2015-2020). The most investigated types were those isolated from umbilical cord blood (hUCB-MSCs), adipose tissue (hAT-MSCs) and bone marrow (hBM-MSCs). The most studied diseases were wounds and ulcers, burns and psoriasis. At preclinical level, in vivo studies with mice and rats were the main animal models used, and a wide range of types of hMSCs were used. Clinical studies analyzed revealed that cell therapy by intravenous administration was the advanced therapy preferred except in the case of wounds and burns where tissue engineering was also reported. Although in most of the clinical trials reviewed results have not been posted yet, safety was high and only local slight adverse events (mild nausea or abdominal pain) were reported. In terms of effectiveness, it was difficult to compare the results due to the different doses administered and variables measured, but in general, percentage of wound's size reduction was higher than 80% in wounds, Psoriasis Area and Severity Index and Severity Scoring for Atopic Dermatitis were significantly reduced, for scleroderma, parameters such as Modified Rodnan skin score (MRSC) or European Scleroderma Study Group activity index reported an improvement of the disease and for hypertrophic scars, Vancouver Scar Scale (VSS) score was decreased after applying these therapies. On balance, hMSCs used for the treatment of cutaneous diseases is a promising strategy, however, the different experimental designs and endpoints stablished in each study, makes necessary more research to find the best way to treat each patient and disease.

Project description:Mesenchymal stromal cells (MSCs) have become the most commonly used adult stem cells in regenerative medicine. Preclinical studies have shown that MSCs-based therapy is a potential new treatment approach for neurological diseases. Intrathecal injection has unique feature which allows stem cells to directly migrate to the lesion site in patients with central nervous system (CNS) diseases. In this study, we evaluate the safety and feasibility of intrathecal allogeneic bone marrow-derived MSCs (BM-MSCs) in patients with neurological diseases. This open-label clinical study included 37 patients (14 diseases). Eligible patients underwent a baseline assessment and were intrathecally injected with allogeneic BM-MSCs (1 × 106 cells/kg, 4 consecutive treatments at 1-week intervals). After four infusions, the patients were followed up for at least 6 months. Adverse events, cerebrospinal fluid (CSF) test results, clinical symptoms, physical examination, and haematological and imaging examinations were used to assess the safety and feasibility of the treatment. Also, we performed a systematic review of the safety of all types of intrathecal stem cells and compared our result to previous studies. In our study, the highest adverse event was a slight ache at the injection site (4.11%), followed by fever (3.42%) and mild headache (2.05%). No severe adverse events were reported. After the intrathecal injections, the white blood cell (WBC) counts in the CSF increased in 30 patients and the protein concentration in the CSF exceeded the normal range in 26 patients, while other CSF indicators remained normal. Moreover, these patients had no suspected manifestations of CNS infection. Haematological and imaging examinations showed no abnormal changes after BM-MSCs infusion. Compared with previous studies, the incidence of adverse events was nearly consistent or even lower for headache, fever, nausea, and neck pain. In conclusion, repeated intrathecal allogeneic BM-MSCs are safe, feasible, and promising for the treatment of patients with neurological diseases.

Dataset Information

Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases.

Publications

Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases.

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