Dataset Information

Combined Adipose Tissue-Derived Mesenchymal Stem Cell Therapy and Rehabilitation in Experimental Stroke.

ABSTRACT: Background/Objective: Stroke is a leading global cause of adult disability. As the population ages as well as suffers co-morbidities, it is expected that the stroke burden will increase further. There are no established safe and effective restorative treatments to facilitate a good functional outcome in stroke patients. Cell-based therapies, which have a wide therapeutic window, might benefit a large percentage of patients, especially if combined with different restorative strategies. In this study, we tested whether the therapeutic effect of human adipose tissue-derived mesenchymal stem cells (ADMSCs) could be further enhanced by rehabilitation in an experimental model of stroke. Methods: Focal cerebral ischemia was induced in adult male Sprague Dawley rats by permanently occluding the distal middle cerebral artery (MCAO). After the intravenous infusion of vehicle (n = 46) or ADMSCs (2 × 106) either at 2 (n = 37) or 7 (n = 7) days after the operation, half of the animals were housed in an enriched environment mimicking rehabilitation. Subsequently, their behavioral recovery was assessed by a neurological score, and performance in the cylinder and sticky label tests during a 42-day behavioral follow-up. At the end of the follow-up, rats were perfused for histology to assess the extent of angiogenesis (RECA-1), gliosis (GFAP), and glial scar formation. Results: No adverse effects were observed during the follow-up. Combined ADMSC therapy and rehabilitation improved forelimb use in the cylinder test in comparison to MCAO controls on post-operative days 21 and 42 (P < 0.01). In the sticky label test, ADMSCs and rehabilitation alone or together, significantly decreased the removal time as compared to MCAO controls on post-operative days 21 and 42. An early initiation of combined therapy seemed to be more effective. Infarct size, measured by MRI on post-operative days 1 and 43, did not differ between the experimental groups. Stereological counting revealed an ischemia-induced increase both in the density of blood vessels and the numbers of glial cells in the perilesional cortex, but there were no differences among MCAO groups. Glial scar volume was also similar in MCAO groups. Conclusion: Early delivery of ADMSCs and combined rehabilitation enhanced behavioral recovery in an experimental stroke model. The mechanisms underlying these treatment effects remain unknown.

SUBMITTER: Mu J

PROVIDER: S-EPMC6443824 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Combined Adipose Tissue-Derived Mesenchymal Stem Cell Therapy and Rehabilitation in Experimental Stroke.

Mu Jingwei J Bakreen Abdulhameed A Juntunen Miia M Korhonen Paula P Oinonen Ella E Cui Lili L Myllyniemi Mikko M Zhao Shanshan S Miettinen Susanna S Jolkkonen Jukka J

Frontiers in neurology 20190326

<b>Background/Objective:</b> Stroke is a leading global cause of adult disability. As the population ages as well as suffers co-morbidities, it is expected that the stroke burden will increase further. There are no established safe and effective restorative treatments to facilitate a good functional outcome in stroke patients. Cell-based therapies, which have a wide therapeutic window, might benefit a large percentage of patients, especially if combined with different restorative strategies. In ...[more]

PMID: 30972000

Similar Datasets

Project description:Periprosthetic joint infection (PJI) is characterized by biofilm infection, which is difficult to alleviate while preserving implant integrity. Furthermore, long-term antibiotic therapy may increase the prevalence of drug-resistant bacterial strains, necessitating a non-antibacterial approach. Adipose-derived stem cells (ADSCs) exert antibacterial effects; however, their efficacy in PJI remains unclear. This study investigates the efficacy of combined intravenous ADSCs and antibiotic therapy in comparison to antibiotic monotherapy in a methicillin-sensitive Staphylococcus aureus (MSSA)-infected PJI rat model. The rats were randomly assigned and equally divided into 3 groups: no-treatment group, antibiotic group, ADSCs with antibiotic group. The ADSCs with antibiotic group exhibited the fastest recovery from weight loss, with lower bacterial counts (p = 0.013 vs. no-treatment group; p = 0.024 vs. antibiotic group) and less bone density loss around the implants (p = 0.015 vs. no-treatment group; p = 0.025 vs. antibiotic group). The modified Rissing score was used to evaluate localized infection on postoperative day 14 and was the lowest in the ADSCs with antibiotic group; however, no significant difference was observed between the antibiotic group and ADSCs with antibiotic group (p < 0.001 vs. no-treatment group; p = 0.359 vs. antibiotic group). Histological analysis revealed a clear, thin, and continuous bony envelope, a homogeneous bone marrow, and a defined, normal interface in the ADSCs with antibiotic group. Moreover, the expression of cathelicidin expression was significantly higher (p = 0.002 vs. no-treatment group; p = 0.049 vs. antibiotic group), whereas that of tumor necrosis factor (TNF)-α and interleukin(IL)-6 was lower in the ADSCs with antibiotic group than in the no-treatment group (TNF-α, p = 0.010 vs. no-treatment group; IL-6, p = 0.010 vs. no-treatment group). Thus, the combined intravenous ADSCs and antibiotic therapy induced a stronger antibacterial effect than antibiotic monotherapy in a MSSA-infected PJI rat model. This strong antibacterial effect may be related to the increased cathelicidin expression and decreased inflammatory cytokine expression at the site of infection.

Project description:Mesenchymal stem cells (MSCs) possess self-renewal and multipotential differentiation abilities, and they are thought to be one of the most reliable stem cell sources for a variety of cell therapies. Recently, cell therapy using MSCs has been studied as a novel therapeutic approach for cancers that show refractory progress and poor prognosis. MSCs from different tissues have different properties. However, the effect of different MSC properties on their application in anticancer therapies has not been thoroughly investigated. In this study, to characterize the anticancer therapeutic application of MSCs from different sources, we established two different kinds of human MSCs: umbilical cord blood-derived MSCs (UCB-MSCs) and adipose-tissue-derived MSCs (AT-MSCs). We used these MSCs in a coculture assay with primary glioblastoma multiforme (GBM) cells to analyze how MSCs from different sources can inhibit GBM growth. We found that UCB-MSCs inhibited GBM growth and caused apoptosis, but AT-MSCs promoted GBM growth. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling assay clearly demonstrated that UCB-MSCs promoted apoptosis of GBM via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL was expressed more highly by UCB-MSCs than by AT-MSCs. Higher mRNA expression levels of angiogenic factors (vascular endothelial growth factor, angiopoietin 1, platelet-derived growth factor, and insulin-like growth factor) and stromal-derived factor-1 (SDF-1/CXCL12) were observed in AT-MSCs, and highly vascularized tumors were developed when AT-MSCs and GBM were cotransplanted. Importantly, CXCL12 inhibited TRAIL activation of the apoptotic pathway in GBM, suggesting that AT-MSCs may support GBM development in vivo by at least two distinct mechanisms-promoting angiogenesis and inhibiting apoptosis. The opposite effects of AT-MSCs and UCB-MSCs on GBM clearly demonstrate that differences must be considered when choosing a stem cell source for safety in clinical application.

Dataset Information

Combined Adipose Tissue-Derived Mesenchymal Stem Cell Therapy and Rehabilitation in Experimental Stroke.

Publications

Combined Adipose Tissue-Derived Mesenchymal Stem Cell Therapy and Rehabilitation in Experimental Stroke.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets