scholarly journals Mesenchymal stem cells for inflammatory airway disorders: promises and challenges

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Xing-Liang Fan ◽  
Zhao Zhang ◽  
Chui Yan Ma ◽  
Qing-Ling Fu
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Clinical Setting ◽  
Lung Diseases ◽  
Preclinical Studies ◽  
Immunomodulatory Effects ◽  
Paracrine Effects ◽  
Clinical Therapy

Abstract The regenerative and immunomodulatory characteristics of mesenchymal stem cells (MSCs) make them attractive in the treatment of many diseases. Although they have shown promising preclinical studies of immunomodulation and paracrine effects in inflammatory airway disorders and other lung diseases, there are still challenges that have to be overcome before MSCs can be safely, effectively, and routinely applied in the clinical setting. A good understanding of the roles and mechanisms of the MSC immunomodulatory effects will benefit the application of MSC-based clinical therapy. In this review, we summarize the promises and challenges of the preclinical and clinical trials of MSC therapies, aiming to better understand the role that MSCs play in attempt to treat inflammatory airway disorders.

scholarly journals Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: a systematic review and implication for clinical application

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yunyu Zhao ◽  
Zhipeng Yan ◽  
Ying Liu ◽  
Yue Zhang ◽  
Jie Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Acute Lung Injury ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Tissue ◽  
Preclinical Studies ◽  
Patient Prognosis

AbstractPulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (− 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.

scholarly journals Dental Tissue-Derived Human Mesenchymal Stem Cells and Their Potential in Therapeutic Application

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Lu Gan ◽  
Ying Liu ◽  
Dixin Cui ◽  
Yue Pan ◽  
Liwei Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Preclinical Studies ◽  
Dental Tissue ◽  
Differentiation Potential ◽  
Dental Tissues ◽  
Lineage Differentiation ◽  
Cell Based Therapy

Human mesenchymal stem cells (hMSCs) are multipotent cells, which exhibit plastic adherence, express specific cell surface marker spectrum, and have multi-lineage differentiation potential. These cells can be obtained from multiple tissues. Dental tissue-derived hMSCs (dental MSCs) possess the ability to give rise to mesodermal lineage (osteocytes, adipocytes, and chondrocytes), ectodermal lineage (neurocytes), and endodermal lineages (hepatocytes). Dental MSCs were first isolated from dental pulp of the extracted third molar and till now they have been purified from various dental tissues, including pulp tissue of permanent teeth and exfoliated deciduous teeth, apical papilla, periodontal ligament, gingiva, dental follicle, tooth germ, and alveolar bone. Dental MSCs are not only easily accessible but are also expandable in vitro with relative genomic stability for a long period of time. Moreover, dental MSCs have exhibited immunomodulatory properties by secreting cytokines. Easy accessibility, multi-lineage differentiation potential, and immunomodulatory effects make dental MSCs distinct from the other hMSCs and an effective tool in stem cell-based therapy. Several preclinical studies and clinical trials have been performed using dental MSCs in the treatment of multiple ailments, ranging from dental diseases to nondental diseases. The present review has summarized dental MSC sources, multi-lineage differentiation capacities, immunomodulatory features, its potential in the treatment of diseases, and its application in both preclinical studies and clinical trials. The regenerative therapeutic strategies in dental medicine have also been discussed.

scholarly journals COVID‐19 hypothesis: Exosomes of mesenchymal stem cells as nano-cargos for anti-SARS-CoV-2 asRNAs

2020 ◽  
Author(s):  
Alireza Afshar ◽  
Masood Zare ◽  
Zohreh Farrar ◽  
Alireza Hashemi ◽  
Arezoo Khoradmehr ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lung Diseases ◽  
Human Lung ◽  
Rna Virus ◽  
Immunomodulatory Effects ◽  
Promising Candidate ◽  
Positive Sense ◽  
Respiratory Epithelial

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 is rapidly spreading worldwide. Scientists are searching to find an effective treatment for coronavirus disease 2019 (COVID-19). Several antiviral drugs are currently undergoing clinical trial studies to evaluate their safety and efficacy in the treatment of COVID-19. SARS-CoV-2 is a positive-sense single-stranded RNA virus. Previous studies showed the efficacy of anti-RNA virus, single strand RNA inhibiting antisense RNAs (asRNAs), on silencing of virus replication, in vitro. To transfer the anti-SARS-CoV-2 asRNAs to human respiratory epithelium, exosomes can be suggested as a promising candidate. Mesenchymal stem cells (MSCs) secret exosomes and they can be loaded by anti-RNA virus asRNAs. MSCs-secreted exosomes as a nano-cargo of anti-SARS-CoV-2 asRNAs have other therapeutic potentials such as immunomodulatory effects of their cytokine contents, affinity to respiratory epithelial attachment, anti-fibrotic activity in lung, non-toxicity for normal cells, and do not trigger an immune response. Inhalation of anti-SARS-CoV-2 asRNAs may stop SARS-CoV-2 replication. Producing a specific anti-SARS-CoV-2 asRNAs by targeting the genome of virus and their delivery by MSCs exosomes is suggested and discussed. This approach potentially sheds light on gene therapy of the other human lung diseases via inhalational delivery using exosomes in future.

scholarly journals Efficacy and Mode of Action of Mesenchymal Stem Cells in Non-Ischemic Dilated Cardiomyopathy: A Systematic Review

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 570
Author(s):  
Cecilie Hoeeg ◽  
Sabina Frljak ◽  
Abbas Ali Qayyum ◽  
Bojan Vrtovec ◽  
Jens Kastrup ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Mode Of Action ◽  
Preclinical Studies ◽  
Gene And Protein Expression ◽  
Non Ischemic Dilated Cardiomyopathy

Non-ischemic dilated cardiomyopathy (NIDCM) constitutes one of the most common causes to non-ischemic heart failure. Despite treatment, the disease often progresses, causing severe morbidity and mortality, making novel treatment strategies necessary. Due to the regenerative actions of mesenchymal stem cells (MSCs), they have been proposed as a treatment for NIDCM. This systematic review aims to evaluate efficacy and mode of action (MoA) of MSC-based therapies in NIDCM. A systematic literature search was conducted in Medline (Pubmed) and Embase. A total of 27 studies were included (3 clinical trials and 24 preclinical studies). MSCs from different tissues and routes of delivery were reported, with bone marrow-derived MSCs and direct intramyocardial injections being the most frequent. All included clinical trials and 22 preclinical trials reported an improvement in cardiac function following MSC treatment. Furthermore, preclinical studies demonstrated alterations in tissue structure, gene, and protein expression patterns, primarily related to fibrosis and angiogenesis. Consequently, MSC treatment can improve cardiac function in NIDCM patients. The MoA underlying this effect involves anti-fibrosis, angiogenesis, immunomodulation, and anti-apoptosis, though these processes seem to be interdependent. These encouraging results calls for larger confirmatory clinical studies, as well as preclinical studies utilizing unbiased investigation of the potential MoA.

scholarly journals Mesenchymal stem cell-derived extracellular vesicles in therapy against fibrotic diseases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuling Huang ◽  
Lina Yang
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Preclinical Studies ◽  
Preclinical Research ◽  
Existing Problems ◽  
Fibrotic Diseases

AbstractFibrosis is likely to occur in many tissues and organs to induce cicatrisation and dysfunction. The therapeutic regimens for delaying and even reversing fibrosis are quite limited at present. In nearly a decade, mesenchymal stem cells (MSCs) have been widely acknowledged as useful in treating fibrotic diseases in preclinical and clinical trials. Further preclinical studies indicated that the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are probably superior to that of MSCs. At present, MSC-EVs have attracted much attention in treating fibrosis of lung, liver, kidney, skin, and heart. By contrast, a significant knowledge-gap remains in treating fibrosis of other tissues and organs (including uterus, gastrointestinal tract, and peritoneum) with the aid of MSC-EVs. This review summarises the preclinical research status of MSC-EVs in treating fibrotic diseases and proposes solutions to existing problems, which contribute to further clinical research on the treatment of fibrotic diseases with MSC-EVs in the future.

scholarly journals Intravenous Administration of Human Amniotic Mesenchymal Stem Cells in the Subacute Phase of Cerebral Infarction in a Mouse Model Ameliorates Neurological Disturbance by Suppressing Blood Brain Barrier Disruption and Apoptosis via Immunomodulation

2021 ◽  
Vol 30 ◽  
pp. 096368972110241
Author(s):  
Yasunori Yoshida ◽  
Toshinori Takagi ◽  
Yoji Kuramoto ◽  
Kotaro Tatebayashi ◽  
Manabu Shirakawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mouse Model ◽  
Cerebral Infarction ◽  
Blood Brain Barrier ◽  
Brain Infarction ◽  
Brain Barrier ◽  
Neurological Deficits ◽  
Immunomodulatory Effects ◽  
Amniotic Mesenchymal Stem Cells

Neuro-inflammation plays a key role in the pathophysiology of brain infarction. Cell therapy offers a novel therapeutic option due to its effect on immunomodulatory effects. Amniotic stem cells, in particular, show promise owing to their low immunogenicity, tumorigenicity, and easy availability from amniotic membranes discarded following birth. We have successfully isolated and expanded human amniotic mesenchymal stem cells (hAMSCs). Herein, we evaluated the therapeutic effect of hAMSCs on neurological deficits after brain infarction as well as their immunomodulatory effects in a mouse model in order to understand their mechanisms of action. One day after permanent occlusion of the middle cerebral artery (MCAO), hAMSCs were intravenously administered. RT-qPCR for TNFα, iNOS, MMP2, and MMP9, immunofluorescence staining for iNOS and CD11b/c, and a TUNEL assay were performed 8 days following MCAO. An Evans Blue assay and behavioral tests were performed 2 days and several months following MCAO, respectively. The results suggest that the neurological deficits caused by cerebral infarction are improved in dose-dependent manner by the administration of hAMSCs. The mechanism appears to be through a reduction in disruption of the blood brain barrier and apoptosis in the peri-infarct region through the suppression of pro-inflammatory cytokines and the M2-to-M1 phenotype shift.

scholarly journals Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001684
Author(s):  
Rafael Moreno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Oncolytic Viruses ◽  
Immunogenic Cell Death ◽  
The Past ◽  
Physical Barriers ◽  
Immunogenic Properties ◽  
New Strategies

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.

Sign in / Sign up

Export Citation Format

Share Document