The Potential of Mesenchymal Stem Cells for the Treatment of Cytokine Storm due to COVID-19

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seriously affected public health and social stability. The main route of the transmission is droplet transmission, where the oral cavity is the most important entry point to the body. Due to both the direct harmful effects of SARS-CoV-2 and disordered immune responses, some COVID-19 patients may progress to acute respiratory distress syndrome or even multiple organ failure. Genetic variants of SARS-CoV-2 have been emerging and circulating around the world. Currently, there is no internationally approved precise treatment for COVID-19. Mesenchymal stem cells (MSCs) can traffic and migrate towards the affected tissue, regulate both the innate and acquired immune systems, and participate in the process of healing. Here, we will discuss and investigate the mechanisms of immune disorder in COVID-19 and the therapeutic activity of MSCs, in particular human gingiva mesenchymal stem cells.

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Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary SuccessOK

Biomedicines ◽

10.3390/biomedicines9060667 ◽

2021 ◽

Vol 9 (6) ◽

pp. 667

Author(s):

Gabriella Racchetti ◽

Jacopo Meldolesi

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune Responses ◽

Extracellular Vesicles ◽

Immune Regulation ◽

Great Increase ◽

The Body ◽

Cell Aging ◽

Therapeutic Effects ◽

Therapeutic Properties

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.

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Successful Treatment of Plaque Psoriasis with Allogeneic Gingival Mesenchymal Stem Cells: A Case Study

Case Reports in Dermatological Medicine ◽

10.1155/2020/4617520 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Sebo Gene Wang ◽

Nicholas C. Hsu ◽

Sebo Michelle Wang ◽

Fu Nan Wang

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Plaque Psoriasis ◽

Inflammatory Diseases ◽

Treatment Options ◽

Gingival Tissue ◽

Complete Regression ◽

Allogeneic Mscs ◽

Human Gingiva

Plaque psoriasis is the most common type of psoriasis that manifests as red scaly patches with white scales affecting body areas including scalp, elbows, knees, trunk, and buttocks. Although many treatment options are available including novel biologics, no cure is available. Mesenchymal stem cells (MSCs) have been safely used to treat a variety of human diseases. Allogeneic MSCs possess unique characteristics including hypoimmunogenicity, immunomodulatory, and anti-inflammatory properties, and they are currently being explored for potential therapeutic use for many systemic inflammatory diseases. The human gingival tissue is an easily accessible and obtainable source for the isolation of MSCs. MSCs from adult human gingiva are of fetal-like phenotype, multipotent, and easy to isolate and expand in vitro. Herein, we report a case of a 19-year-old man with a 5-year history of severe plaque psoriasis refractory to multiple topical and systemic therapies who was treated with allogeneic human gingival MSCs. Complete regression was achieved after 5 infusions with no adverse reaction occurred. The patient has been followed for three years and has remained disease free.

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A Role of Tumor-Released Exosomes in Paracrine Dissemination and Metastasis

International Journal of Molecular Sciences ◽

10.3390/ijms19123968 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3968 ◽

Cited By ~ 17

Author(s):

Enrico Spugnini ◽

Mariantonia Logozzi ◽

Rossella Di Raimo ◽

Davide Mizzoni ◽

Stefano Fais

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

The Body ◽

Mesenchymal Transition ◽

Metastatic Cascade ◽

Target Organs

Metastatic diffusion is thought to be a multi-step phenomenon involving the release of cells from the primary tumor and their diffusion through the body. Currently, several hypotheses have been put forward in order to explain the origin of cancer metastasis, including epithelial–mesenchymal transition, mutagenesis of stem cells, and a facilitating role of macrophages, involving, for example, transformation or fusion hybridization with neoplastic cells. In this paradigm, tumor-secreted extracellular vesicles (EVs), such as exosomes, play a pivotal role in cell communications, delivering a plethora of biomolecules including proteins, lipids, and nucleic acids. For their natural role in shuttling molecules, EVs have been newly considered a part of the metastatic cascade. They have a prominent role in preparing the so-called “tumor niches” in target organs. However, recent evidence has pointed out an even more interesting role of tumor EVs, consisting in their ability to induce malignant transformation in resident mesenchymal stem cells. All in all, in this review, we discuss the multiple involvements of EVs in the metastatic cascade, and how we can exploit and manipulate EVs in order to reduce the metastatic spread of malignant tumors.

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The Latest Developments in Immunomodulation of Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions, Both Allogeneic and Autologous

Frontiers in Immunology ◽

10.3389/fimmu.2021.785717 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jia-ming Chen ◽

Qiao-yi Huang ◽

Yun-xia Zhao ◽

Wei-hong Chen ◽

Shu Lin ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mhc Class I ◽

Mhc Class Ii ◽

The Body ◽

Immune Rejection ◽

Intrauterine Adhesions ◽

Allogeneic Mscs ◽

Intrauterine Adhesion ◽

Low Levels

Intrauterine adhesion (IUA) is an endometrial fibrosis disease caused by repeated operations of the uterus and is a common cause of female infertility. In recent years, treatment using mesenchymal stem cells (MSCs) has been proposed by many researchers and is now widely used in clinics because of the low immunogenicity of MSCs. It is believed that allogeneic MSCs can be used to treat IUA because MSCs express only low levels of MHC class I molecules and no MHC class II or co-stimulatory molecules. However, many scholars still believe that the use of allogeneic MSCs to treat IUA may lead to immune rejection. Compared with allogeneic MSCs, autologous MSCs are safer, more ethical, and can better adapt to the body. Here, we review recently published articles on the immunomodulation of allogeneic and autologous MSCs in IUA therapy, with the aim of proving that the use of autologous MSCs can reduce the possibility of immune rejection in the treatment of IUAs.

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Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2010.01.126 ◽

2010 ◽

Vol 393 (3) ◽

pp. 377-383 ◽

Cited By ~ 178

Author(s):

Geetanjali B. Tomar ◽

Rupesh K. Srivastava ◽

Navita Gupta ◽

Amruta P. Barhanpurkar ◽

Satish T. Pote ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Regenerative Medicine ◽

Cell Therapy ◽

Human Gingiva

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Human gingiva-derived mesenchymal stem cells are therapeutic in lupus nephritis through targeting of CD39−CD73 signaling pathway

Journal of Autoimmunity ◽

10.1016/j.jaut.2020.102491 ◽

2020 ◽

Vol 113 ◽

pp. 102491

Author(s):

Junlong Dang ◽

Zhenjian Xu ◽

Anping Xu ◽

Yan Liu ◽

Qingling Fu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lupus Nephritis ◽

Signaling Pathway ◽

Human Gingiva

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Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

Sultan Qaboos University Medical Journal [SQUMJ] ◽

10.18295/squmj.2018.18.03.002 ◽

2018 ◽

Vol 18 (3) ◽

pp. 264 ◽

Cited By ~ 52

Author(s):

Roberto Berebichez-Fridman ◽

Pablo R. Montero-Olvera

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Regenerative Medicine ◽

Adult Stem Cells ◽

Current Knowledge ◽

Clinical Applications ◽

The Body ◽

Differentiation Potential ◽

Advantages And Disadvantages

First discovered by Friedenstein in 1976, mesenchymal stem cells (MSCs) are adult stem cells found throughout the body that share a fixed set of characteristics. Discovered initially in the bone marrow, this cell source is considered the gold standard for clinical research, although various other sources—including adipose tissue, dental pulp, mobilised peripheral blood and birth-derived tissues—have since been identified. Although similar, MSCs derived from different sources possess distinct characteristics, advantages and disadvantages, including their differentiation potential and proliferation capacity, which influence their applicability. Hence, they may be used for specific clinical applications in the fields of regenerative medicine and tissue engineering. This review article summarises current knowledge regarding the various sources, characteristics and therapeutic applications of MSCs.Keywords: Mesenchymal Stem Cells; Adult Stem Cells; Regenerative Medicine; Cell Differentiation; Tissue Engineering.

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Mesenchymal Stem Cells Derived from Healthy and Diseased Human Gingiva Support Osteogenesis on Electrospun Polycaprolactone Scaffolds

Bioengineering ◽

10.3390/bioengineering5010008 ◽

2018 ◽

Vol 5 (1) ◽

pp. 8 ◽

Cited By ~ 7

Author(s):

Catherine Jauregui ◽

Suyog Yoganarasimha ◽

Parthasarathy Madurantakam

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Gingiva

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In vivo tracking of intravenously injected mesenchymal stem cells in an Alzheimer’s animal model

Cell Transplantation ◽

10.1177/0963689718788067 ◽

2018 ◽

Vol 27 (8) ◽

pp. 1203-1209

Author(s):

Bok-Nam Park ◽

Tae Sung Lim ◽

Joon-Kee Yoon ◽

Young-Sil An

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Animal Model ◽

Mesenchymal Stem Cells ◽

Gamma Camera ◽

The Body ◽

Control Group ◽

Indium 111 ◽

The Brain

Purpose: The purpose of this study was to investigate how intravenously injected bone marrow-derived mesenchymal stem cells (BMSCs) are distributed in the body of an Alzheimer’s disease (AD) animal model. Methods: Stem cells were collected from bone marrow of mice and labeled with Indium-111 (111In). The 111In-labeled BMSCs were infused intravenously into 3×Tg-AD mice in the AD group and non-transgenic mice (B6129SF2/J) as controls. Biodistribution was evaluated with a gamma counter and gamma camera 24 and 48 h after injecting the stem cells. Results: A gamma count of the brain showed a higher distribution of labeled cells in the AD model than in the control group at 24 (p = .0004) and 48 h (p = .0016) after injection of the BMSCs. Similar results were observed by gamma camera imaging (i.e., brain uptake in the AD model was significantly higher than that in the control group). Among the other organs, uptake by the spleen was the highest in both groups. More BMSCs were found in the lungs of the control group than in those of the AD group. Conclusions: These results suggest that more intravenously infused BMSCs reached the brain in the AD model than in the control group, but the numbers of stem cells reaching the brain was very small.

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