scholarly journals Immunomodulatory Potential of Human Mesenchymal Stem Cells and their Exosomes on Multiple Sclerosis

2021 ◽  
Author(s):  
Hussein Baharlooi ◽  
Zahra Salehi ◽  
Moein Minbashi Moeini ◽  
Nima Rezaei ◽  
Maryam Azimi
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Interleukin 17 ◽  
Healthy Individuals ◽  
Healthy Control ◽  
Multiple Sclerosis Patients

Purpose: Promising advances have been made in mesenchymal stem cell transplantation to re-induce the immune tolerance in neuroinflammatory animal models and Multiple Sclerosis patients. The available evidence demonstrated that immunomodulatory effects of mesenchymal stem cell are particularly exerted through releasing exosomes to their environment. We therefore, aimed to comparatively assess the potential effect of mesenchymal stem cells and mesenchymal stem cells-derived exosomes on proliferation and function of the CD4+CD25− conventional T cells, isolated from relapsing-remitting Multiple Sclerosis patients. Methods: Mesenchymal stem cells were isolated from human umbilical cord tissues and used for exosome isolation via ultracentrifugation. Both mesenchymal stem cells and mesenchymal stem cells-derived exosomes were evaluated for their anti-inflammatory effects against the proliferation of T cells isolated from two groups of individuals in vitro, MS patients and healthy subjects. Cytokine production of conventional T cells (interferon-γ, interleukin-10, and interleukin-17) was also assessed, using flow cytometry for the patients and healthy individuals. Results: Here, evidence shows that MSCs and MSC-derived exosomes dampen proliferation and percentage of conventional T cells that produce IFN-γ (healthy control: p<0.001) and interleukin-17 (healthy control: p<0.001, MS patients: p<0.001), with a significant increase of IL-10 producing cells in the patients and healthy individuals. Surprisingly, MSC-derived exosomes demonstrated higher immune-modulating properties on conventional T cells responses, compared to MSCs. Conclusion: The current study, provides a novel approach of exocytosis on autoimmune therapy. In particular, Mesenchymal stem cell -derived exosomes, which are cell-derived biologics, could be considered as an alternative for Mesenchymal stem cells in treating multiple sclerosis.

scholarly journals Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis

2018 ◽  
Vol 4 (1) ◽  
pp. 205521731876528 ◽  
Author(s):  
Sarah M Planchon ◽  
Karen T Lingas ◽  
Jane Reese Koç ◽  
Brittney M Hooper ◽  
Basabi Maitra ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Cell Culture ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Phase I ◽  
Mesenchymal Stem Cell Culture ◽  
Stem Cell Culture ◽  
Multiple Sclerosis Patients

Background Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients’ mesenchymal stem cells for clinical trials is limited. Objective To determine the feasibility of culture-expanding multiple sclerosis patients’ mesenchymal stem cells for clinical use. Methods In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1–2 × 106 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. Results One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16–62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Conclusion Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

scholarly journals Hydrogen Sulfide Regulates Homeostasis of Mesenchymal Stem Cells and Regulatory T Cells

2016 ◽  
Vol 95 (13) ◽  
pp. 1445-1451 ◽  
Author(s):  
R. Yang ◽  
Y. Liu ◽  
S. Shi
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Hydrogen Sulfide ◽  
Mesenchymal Stem Cell ◽  
Tissue Homeostasis ◽  
Cell Functions ◽  
Multiple Signaling ◽  
Pathologic Processes

Hydrogen sulfide (H2S) has long been known as a toxic gas. However, recently accumulated evidence suggests that H2S contributes to a variety of physiologic and pathologic processes. Endogenous H2S production is regulated by multiple enzymes that are differentially expressed in the cardiovascular, neuronal, immune, renal, respiratory, gastrointestinal, reproductive, liver, and endocrine systems. Alteration of H2S metabolism may affect multiple signaling pathways and tissue homeostasis. The growing number of diverse targets for which H2S serves as a gasotransmitter has been extensively reviewed elsewhere. In this review, the authors discuss current emerging evidence that H2S regulates mesenchymal stem cell and T-cell functions.

The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: consensus report of the International MSCT Study Group

2010 ◽  
Vol 16 (4) ◽  
pp. 503-510 ◽  
Author(s):  
Mark S Freedman ◽  
Amit Bar-Or ◽  
Harold L Atkins ◽  
Dimitrios Karussis ◽  
Francesco Frassoni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Mesenchymal Stem Cell Transplantation

Current therapies for multiple sclerosis effectively reduce inflammation, but do little in terms of repair to the damaged central nervous system. Cell-based therapies may provide a new strategy for bolstering regeneration and repair through neuro-axonal protection or remyelination. Mesenchymal stem cells modulate pathological responses in experimental autoimmune encephalitis, alleviating disease, but also stimulate repair of the central nervous system through the release of soluble factors. Autologous and allogeneic mesenchymal stem cells have been safely administered to individuals with hemato-oncological diseases and in a limited number of patients with multiple sclerosis. It is therefore reasonable to move mesenchymal stem cells transplantation into properly controlled human studies to explore their potential as a treatment for multiple sclerosis. Since it is likely that the first such studies will probably involve only small numbers of patients in a few centers, we formed an international panel comprising multiple sclerosis neurology and stem cell experts, as well as immunologists. The aims were to derive a consensus on the utilization of mesenchymal stem cells for the treatment of multiple sclerosis, along with protocols for the culture of the cells and the treatment of patients. This article reviews the consensus derived from our group on the rationale for mesenchymal stem cell transplantation, the methodology for generating mesenchymal stem cells and the first treatment protocol for multiple sclerosis patients.

scholarly journals Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-β

2010 ◽  
Vol 184 (10) ◽  
pp. 5885-5894 ◽  
Author(s):  
Shyam A. Patel ◽  
Justin R. Meyer ◽  
Steven J. Greco ◽  
Kelly E. Corcoran ◽  
Margarette Bryan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Regulatory T Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells

Mesenchymal Stem Cells in the Treatment of Cartilage Defects of the Knee: A Systematic Review of the Clinical Outcomes

2021 ◽  
pp. 036354652098681
Author(s):  
Monketh Jaibaji ◽  
Rawan Jaibaji ◽  
Andrea Volpin
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Osteochondral Lesions ◽  
Common Source ◽  
Significant Heterogeneity ◽  
Osteochondral Defects

Background: Osteochondral lesions are a common clinical problem and their management has been historically challenging. Mesenchymal stem cells have the potential to differentiate into chondrocytes and thus restore hyaline cartilage to the defect, theoretically improving clincal outcomes in these patients. They can also be harvested with minimal donor site morbidity. Purpose: To assess the clinical and functional outcomes of mesenchymal stem cell implantation to treat isolated osteochondral defects of the knee. A secondary purpose is to assess the quality of the current available evidence as well as the radiological and histological outcomes. We also reviewed the cellular preparation and operative techniques for implantation. Study Design: Systematic review. Methods: A comprehensive literature search of 4 databases was carried out: CINAHL, Embase, MEDLINE, and PubMed. We searched for clinical studies reporting the outcomes on a minimum of 5 patients with at least 12 months of follow-up. Clinical, radiological, and histological outcomes were recorded. We also recorded demographics, stem cell source, culture technique, and operative technique. Methodological quality of each study was assessed using the modified Coleman methodology score, and risk of bias for the randomized controlled studies was assessed using the Cochrane Collaboration tool. Results: Seventeen studies were found, encompassing 367 patients. The mean patient age was 35.1 years. Bone marrow was the most common source of stem cells utilized. Mesenchymal stem cell therapy consistently demonstrated good short- to medium-term outcomes in the studies reviewed with no serious adverse events being recorded. There was significant heterogeneity in cell harvesting and preparation as well as in the reporting of outcomes. Conclusion: Mesenchymal stem cells demonstrated a clinically relevant improvement in outcomes in patients with osteochondral defects of the knee. More research is needed to establish an optimal treatment protocol, long-term outcomes, and superiority over other therapies. Registration: CRD42020179391 (PROSPERO).

scholarly journals Synergy of molecularly mobile polyrotaxane surfaces with endothelial cell co-culture for mesenchymal stem cell mineralization

RSC Advances ◽  
2021 ◽  
Vol 11 (30) ◽  
pp. 18685-18692
Author(s):  
Hiroki Masuda ◽  
Yoshinori Arisaka ◽  
Masahiro Hakariya ◽  
Takanori Iwata ◽  
Tetsuya Yoda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Endothelial Cell ◽  
Mesenchymal Stem Cell ◽  
Molecular Mobility ◽  
Culture System

Molecular mobility of polyrotaxane surfaces promoted mineralization in a co-culture system of mesenchymal stem cells and endothelial cells.

scholarly journals Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Xiaoyu Pu ◽  
Siyang Ma ◽  
Yan Gao ◽  
Tiankai Xu ◽  
Pengyu Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Radiation Damage ◽  
Therapeutic Potential ◽  
Damage Model ◽  
Bioactive Substances ◽  
Radiation Induced ◽  
Insight Into

Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

scholarly journals Cytotoxic Effect of Hypoxic Environment in Mesenchymal Stem Cell

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1592
Author(s):  
Sevil Özer ◽  
H. Seda Vatansever ◽  
Feyzan Özdal-Kurt
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Human Mesenchymal Stem Cells ◽  
Hypoxic Condition ◽  
Immunoperoxidase Technique ◽  
Cellular Functions ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BM-MSCs) are used to repair hypoxic or ischemic tissue. After hypoxic the level of ATP is decreases, cellular functions do not continue and apoptosis or necrosis occur. Apoptosis is a progress of programmed cell death that occurs in normal or pathological conditions. In this study, we were investigated the hypoxic effect on apoptosis in mesenchymal stem cell. Bone marrow-derived stem cells were cultured in hypoxic (1% or 3%) or normoxic conditions 24, 96 well plates for 36 h. Cell viability was shown by MTT assay on 36 h. After fixation of cells with 4% paraformaldehyde, distributions of caspase-3, Bcl-2 and Bax with indirect immunoperoxidase technique, apoptotic cells with TUNEL assay were investigated. All staining results were evaluated using H-score analyses method with ANOVA, statistically. As a result, hypoxic condition was toxic for human mesenchymal stem cells and the number of death cell was higher in that than normoxic condition.

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