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1.
Stem Cell Rev Rep ; 18(5): 1525-1545, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1763475

ABSTRACT

Human mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are important adult stem cells for regenerative medicine, largely due to their regenerative characteristics such as self-renewal, secretion of trophic factors, and the capability of inducing mesenchymal cell lineages. MSCs also possess homing and trophic properties modulating immune system, influencing microenvironment around damaged tissues and enhancing tissue repair, thus offering a broad perspective in cell-based therapies. Therefore, it is not surprising that MSCs have been the broadly used adult stem cells in clinical trials. To gain better insights into the current applications of MSCs in clinical applications, we perform a comprehensive review of reported data of MSCs clinical trials conducted globally. We summarize the biological effects and mechanisms of action of MSCs, elucidating recent clinical trials phases and findings, highlighting therapeutic effects of MSCs in several representative diseases, including neurological, musculoskeletal diseases and most recent Coronavirus infectious disease. Finally, we also highlight the challenges faced by many clinical trials and propose potential solutions to streamline the use of MSCs in routine clinical applications and regenerative medicine.


Subject(s)
Adult Stem Cells , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Adult , Cell- and Tissue-Based Therapy , Humans , Regenerative Medicine
2.
Int J Mol Sci ; 22(21)2021 Nov 07.
Article in English | MEDLINE | ID: covidwho-1512380

ABSTRACT

Heparin and its derivatives are saving thousands of human lives annually, by successfully preventing and treating thromboembolic events. Although the mode of action during anticoagulation is well studied, their influence on cell behavior is not fully understood as is the risk of bleeding and other side effects. New applications in regenerative medicine have evolved supporting production of cell-based therapeutics or as a substrate for creating functionalized matrices in biotechnology. The currently resurgent interest in heparins is related to the expected combined anti-inflammatory, anti-thrombotic and anti-viral action against COVID-19. Based on a concise summary of key biochemical and clinical data, this review summarizes the impact for manufacturing and application of cell therapeutics and highlights the need for discriminating the different heparins.


Subject(s)
Anticoagulants/chemistry , Cell- and Tissue-Based Therapy/methods , Heparin/analogs & derivatives , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Cell Adhesion , Hemorrhage/etiology , Heparin/adverse effects , Heparin/therapeutic use , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Regenerative Medicine , Thromboembolism/drug therapy
3.
Cells ; 10(11)2021 11 10.
Article in English | MEDLINE | ID: covidwho-1512137

ABSTRACT

Personalized regenerative medicine and biomedical research have been galvanized and revolutionized by human pluripotent stem cells in combination with recent advances in genomics, artificial intelligence, and genome engineering. More recently, we have witnessed the unprecedented breakthrough life-saving translation of mRNA-based vaccines for COVID-19 to contain the global pandemic and the investment in billions of US dollars in space exploration projects and the blooming space-tourism industry fueled by the latest reusable space vessels. Now, it is time to examine where the translation of pluripotent stem cell research stands currently, which has been touted for more than the last two decades to cure and treat millions of patients with severe debilitating degenerative diseases and tissue injuries. This review attempts to highlight the accomplishments of pluripotent stem cell research together with cutting-edge genomics and genome editing tools and, also, the promises that have still not been transformed into clinical applications, with cardiovascular research as a case example. This review also brings to our attention the scientific and socioeconomic challenges that need to be effectively addressed to see the full potential of pluripotent stem cells at the clinical bedside.


Subject(s)
Cardiovascular Diseases/therapy , Genomics , Pluripotent Stem Cells/transplantation , Artificial Intelligence , Cardiovascular Diseases/genetics , Cardiovascular Diseases/pathology , Cardiovascular System/cytology , Cardiovascular System/growth & development , Cell Differentiation , Drug Discovery , Gene Editing , Humans , Models, Biological , Pluripotent Stem Cells/cytology , Precision Medicine , Regenerative Medicine , Safety
4.
Adv Drug Deliv Rev ; 179: 114007, 2021 12.
Article in English | MEDLINE | ID: covidwho-1482395

ABSTRACT

In recent years, nucleic acid-based therapeutics have gained increasing importance as novel treatment options for disease prevention and treatment. Synthetic messenger RNAs (mRNAs) are promising nucleic acid-based drugs to transiently express desired proteins that are missing or defective. Recently, synthetic mRNA-based vaccines encoding viral proteins have been approved for emergency use against COVID-19. Various types of vehicles, such as lipid nanoparticles (LNPs) and liposomes, are being investigated to enable the efficient uptake of mRNA molecules into desired cells. In addition, the introduction of novel chemical modifications into mRNAs increased the stability, enabled the modulation of nucleic acid-based drugs, and increased the efficiency of mRNA-based therapeutic approaches. In this review, novel and innovative strategies for the delivery of synthetic mRNA-based therapeutics for tissue regeneration are discussed. Moreover, with this review, we aim to highlight the versatility of synthetic mRNA molecules for various applications in the field of regenerative medicine and also discuss translational challenges and required improvements for mRNA-based drugs.


Subject(s)
Drug Delivery Systems , RNA, Messenger/administration & dosage , Regeneration , Regenerative Medicine/trends , Animals , COVID-19 Vaccines/administration & dosage , Gene Transfer Techniques , Genetic Therapy , Humans , RNA, Messenger/immunology
5.
Cells ; 10(11)2021 10 25.
Article in English | MEDLINE | ID: covidwho-1480601

ABSTRACT

As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.


Subject(s)
COVID-19/complications , COVID-19/therapy , Multiple Organ Failure/etiology , Multiple Organ Failure/therapy , Stem Cell Transplantation , COVID-19/immunology , Clinical Trials as Topic , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Humans , Immunomodulation , Multiple Organ Failure/immunology , Regenerative Medicine , SARS-CoV-2/pathogenicity , Stem Cells/cytology , Stem Cells/immunology
6.
Adv Drug Deliv Rev ; 179: 114002, 2021 12.
Article in English | MEDLINE | ID: covidwho-1465981

ABSTRACT

After thirty years of intensive research shaping and optimizing the technology, the approval of the first mRNA-based formulation by the EMA and FDA in order to stop the COVID-19 pandemic was a breakthrough in mRNA research. The astonishing success of these vaccines have brought the mRNA platform into the spotlight of the scientific community. The remarkable persistence of the groundwork is mainly attributed to the exceptional benefits of mRNA application, including the biological origin, immediate but transitory mechanism of action, non-integrative properties, safe and relatively simple manufacturing as well as the flexibility to produce any desired protein. Based on these advantages, a practical implementation of in vitro transcribed mRNA has been considered in most areas of medicine. In this review, we discuss the key preconditions for the rise of the mRNA in the medical field, including the unique structural and functional features of the mRNA molecule and its vehicles, which are crucial aspects for a production of potent mRNA-based therapeutics. Further, we focus on the utility of mRNA tools particularly in the scope of regenerative medicine, i.e. cell reprogramming approaches or manipulation strategies for targeted tissue restoration. Finally, we highlight the strong clinical potential but also the remaining hurdles to overcome for the mRNA-based regenerative therapy, which is only a few steps away from becoming a reality.


Subject(s)
Cell- and Tissue-Based Therapy/methods , RNA, Messenger/therapeutic use , Regenerative Medicine/trends , Tissue Engineering/methods , Animals , COVID-19 , Humans
7.
Cells ; 10(10)2021 09 24.
Article in English | MEDLINE | ID: covidwho-1438525

ABSTRACT

The objective of this review is to describe the evolution of lung tissue-derived diploid progenitor cell applications, ranging from historical biotechnological substrate functions for vaccine production and testing to current investigations around potential therapeutic use in respiratory tract regenerative medicine. Such cell types (e.g., MRC-5 or WI-38 sources) were extensively studied since the 1960s and have been continuously used over five decades as safe and sustainable industrial vaccine substrates. Recent research and development efforts around diploid progenitor lung cells (e.g., FE002-Lu or Walvax-2 sources) consist in qualification for potential use as optimal and renewed vaccine production substrates and, alternatively, for potential therapeutic applications in respiratory tract regenerative medicine. Potentially effective, safe, and sustainable cell therapy approaches for the management of inflammatory lung diseases or affections and related symptoms (e.g., COVID-19 patients and burn patient severe inhalation syndrome) using local homologous allogeneic cell-based or cell-derived product administrations are considered. Overall, lung tissue-derived progenitor cells isolated and produced under good manufacturing practices (GMP) may be used with high versatility. They can either act as key industrial platforms optimally conforming to specific pharmacopoeial requirements or as active pharmaceutical ingredients (API) for potentially effective promotion of lung tissue repair or regeneration.


Subject(s)
Biotechnology/methods , Diploidy , Lung/cytology , Regenerative Medicine/methods , Respiratory Tract Infections/therapy , Animals , Biological Specimen Banks , COVID-19 Vaccines , Cell Line , Cell- and Tissue-Based Therapy , History, 20th Century , History, 21st Century , Humans , Lung/physiology , Regeneration , Regenerative Medicine/history , SARS-CoV-2 , Stem Cell Transplantation , Stem Cells/cytology , Transplantation, Homologous
8.
Stem Cells Transl Med ; 10(10): 1365-1371, 2021 10.
Article in English | MEDLINE | ID: covidwho-1432475

ABSTRACT

In its 2019 report, The Skilled Technical Workforce: Crafting America's Science and Engineering Enterprise, the National Science Board recommended a national charge to create a skilled technical workforce (STW) driven by science and engineering. The RegenMed Development Organization (ReMDO), through its RegeneratOR Workforce Development Initiative, has taken on this challenge beginning with an assessment of regenerative medicine (RM) biomanufacturing knowledge, skills, and abilities (KSAs) needed for successful employment. While STW often refers only to associate degree or other prebaccalaureate prepared technicians, the RM biomanufacturing survey included responses related to baccalaureate prepared technicians. Three levels of preparation were articulated in the research: basic employability skills, core bioscience skills, and RM biomanufacturing technical skills. The first two of these skill levels have been defined by previous research and are generally accepted as foundational-the Common Employability Skills developed by the National Network of Business and Industry Associations and the Core Skill Standards for Bioscience Technicians developed by the National Center for the Biotechnology Workforce. Fifteen skill sets addressing the specialized needs of RM and related biotechnology sectors were identified in the ReMDO survey, defining a third level of KSAs needed for entry-level employment in RM biomanufacturing. The purpose of the article is to outline the KSAs necessary for RM biomanufacturing, quantify the skills gap that currently exists between skills required by employers and those acquired by employees and available in the labor market, and make recommendations for the application of these findings.


Subject(s)
Regenerative Medicine , Surveys and Questionnaires , Workforce
9.
Cells ; 10(8)2021 08 01.
Article in English | MEDLINE | ID: covidwho-1348603

ABSTRACT

Exosomes are a type of extracellular vesicles, produced within multivesicular bodies, that are then released into the extracellular space through a merging of the multivesicular body with the plasma membrane. These vesicles are secreted by almost all cell types to aid in a vast array of cellular functions, including intercellular communication, cell differentiation and proliferation, angiogenesis, stress response, and immune signaling. This ability to contribute to several distinct processes is due to the complexity of exosomes, as they carry a multitude of signaling moieties, including proteins, lipids, cell surface receptors, enzymes, cytokines, transcription factors, and nucleic acids. The favorable biological properties of exosomes including biocompatibility, stability, low toxicity, and proficient exchange of molecular cargos make exosomes prime candidates for tissue engineering and regenerative medicine. Exploring the functions and molecular payloads of exosomes can facilitate tissue regeneration therapies and provide mechanistic insight into paracrine modulation of cellular activities. In this review, we summarize the current knowledge of exosome biogenesis, composition, and isolation methods. We also discuss emerging healing properties of exosomes and exosomal cargos, such as microRNAs, in brain injuries, cardiovascular disease, and COVID-19 amongst others. Overall, this review highlights the burgeoning roles and potential applications of exosomes in regenerative medicine.


Subject(s)
Exosomes/metabolism , Mesenchymal Stem Cells/metabolism , Regenerative Medicine , Animals , Exosomes/physiology , Humans , Mesenchymal Stem Cells/physiology , Tissue Engineering
10.
Int J Mol Sci ; 22(16)2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1341694

ABSTRACT

The current coronavirus disease-19 (COVID-19) pandemic has strongly revived the pressing need to incorporate new therapeutic alternatives to deal with medical situations that result in a dramatic breakdown in the body's normal homeostasis [...].


Subject(s)
Acute Disease/therapy , COVID-19/therapy , Emergency Treatment/methods , Mesenchymal Stem Cell Transplantation/methods , Regenerative Medicine/methods , Acute Disease/mortality , COVID-19/mortality , Clinical Trials as Topic , Emergency Service, Hospital , Emergency Treatment/trends , Humans , Mesenchymal Stem Cell Transplantation/trends , Regenerative Medicine/trends , Survival Rate , Treatment Outcome
11.
J Cereb Blood Flow Metab ; 41(10): 2797-2799, 2021 10.
Article in English | MEDLINE | ID: covidwho-1288495

ABSTRACT

The last 50 years have witnessed the translation of stem cell therapy from the laboratory to the clinic for treating brain disorders, in particular stroke. From the focal stereotaxic transplantation to the minimally invasive intravenous and intraarterial delivery, stem cells display the ability to replenish injured cells and to secrete therapeutic molecules, altogether promoting brain repair. The increased stroke incidence in COVID-19 survivors poses as a new disease indication for cell therapy, owing in part to the cells' robust anti-inflammatory properties. Optimization of the cell transplant regimen will ensure the safe and effective clinical application of cell therapy in stroke and relevant neurological disorders.


Subject(s)
COVID-19/complications , Stem Cell Transplantation , Stroke/etiology , Stroke/therapy , Animals , Brain/pathology , COVID-19/diagnosis , Humans , Incidence , Regenerative Medicine/methods , SARS-CoV-2/isolation & purification , Stem Cell Transplantation/methods , Stroke/pathology
12.
Front Immunol ; 12: 659621, 2021.
Article in English | MEDLINE | ID: covidwho-1285289

ABSTRACT

Methods for suppressing the host immune system over the long term and improving transplantation tolerance remain a primary issue in organ transplantation. Cell therapy is an emerging therapeutic strategy for immunomodulation after transplantation. Mesenchymal stem cells (MSCs) are adult multipotent stem cells with wide differentiation potential and immunosuppressive properties, which are mostly used in regenerative medicine and immunomodulation. In addition, emerging research suggests that MSC-derived exosomes have the same therapeutic effects as MSCs in many diseases, while avoiding many of the risks associated with cell transplantation. Their unique immunomodulatory properties are particularly important in the immune system-overactive graft environment. In this paper, we review the effects of MSC-derived exosomes in the immune regulation mechanism after organ transplantation and graft-versus-host disease (GvHD) from various perspectives, including immunosuppression, influencing factors, anti-inflammatory properties, mediation of tissue repair and regeneration, and the induction of immune tolerance. At present, the great potential of MSC-derived exosomes in immunotherapy has attracted a great deal of attention. Furthermore, we discuss the latest insights on MSC-derived exosomes in organ transplantation and GvHD, especially its commercial production concepts, which aim to provide new strategies for improving the prognosis of organ transplantation patients.


Subject(s)
Exosomes/immunology , Immunomodulation/immunology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/immunology , Organ Transplantation/methods , Transplantation Tolerance/immunology , Adult , Exosomes/metabolism , Graft vs Host Disease/immunology , Humans , Mesenchymal Stem Cells/metabolism , Regenerative Medicine/methods
13.
OMICS ; 25(6): 342-357, 2021 06.
Article in English | MEDLINE | ID: covidwho-1266096

ABSTRACT

Early cell biology reports demonstrated the presence of cells with stem-like properties in bone marrow, with both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multilineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and versatile potentials, MSCs are leveraged in many applications in medicine such as oncology, bioprinting, and as recent as therapeutics discovery and innovation for COVID-19. To date, studies indicate that MSCs have varied differentiation capabilities into different cell types, and demonstrate immunomodulating and anti-inflammatory properties. Different microenvironments or niche for MSCs and their resulting heterogeneity may influence attendant cellular behavior and differentiation capacity. The potential clinical applications of MSCs and exosomes derived from these cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. There is ample reason to think, as discussed in this expert review that the future looks bright and promising for MSC research, with many clinical trials under way to ascertain their clinical utility. This review provides a synthesis of the latest advances and trends in MSC research to allow for broad and critically informed use of MSCs. Early observations of the presence of these cells in the bone marrow and their remarkable differentiation capabilities and immunomodulation are also presented.


Subject(s)
Cell Differentiation , Immunomodulation , Mesenchymal Stem Cells/immunology , Humans , Mesenchymal Stem Cells/physiology , Regenerative Medicine , Stem Cell Niche , Tissue Engineering
15.
Int J Environ Res Public Health ; 18(11)2021 Jun 05.
Article in English | MEDLINE | ID: covidwho-1259492

ABSTRACT

BACKGROUND: Research in the fields of musculoskeletal tissue engineering and regenerative medicine may suffer a slowdown during the ongoing COVID-19 pandemic emergency. This is likely to harm the development of new therapeutic strategies and their translation into the clinic in the long term. Recently, the need to maintain continuity in research activities in those fields has assumed even greater importance due to the accumulation of data concerning the effects of SARS-CoV-2 on the musculoskeletal system. This study is aimed at the identification of a series of safe handling practices against COVID-19 diffusion to apply in a research environment, thus allowing the maintenance of research lab activities. METHODS: The control measures to apply to mitigate the COVID-19 risk were identified and categorized utilizing the Hierarchy of Controls. We also compared our analysis with that assessed before the pandemic to consider the additional risk of COVID-19. RESULTS: Results highlighted that the most relevant implemented measures to control SARS-CoV-2 were based on protecting people through engineering (e.g., ventilation and social distancing), and administrative (e.g., hand sanitization, work shifts) measures or Personnel Protective Equipment, rather than eliminating hazards at the source (e.g., smart working). CONCLUSIONS: Work continuity in research labs during the COVID-19 emergency should be guaranteed by ensuring the protection of researchers in the workplace and considering the physical environment, the type of operators and work activity, and the proven ability of workers to face biological risks. The increased knowledge and awareness on lab' risks should be useful to prevent and mitigate future viral outbreaks.


Subject(s)
COVID-19 , Pandemics , Humans , Regenerative Medicine , SARS-CoV-2 , Workplace
16.
Stem Cell Res Ther ; 12(1): 95, 2021 01 30.
Article in English | MEDLINE | ID: covidwho-1055835

ABSTRACT

Organoids are derived from stem cells or organ-specific progenitors. They display structures and functions consistent with organs in vivo. Multiple types of organoids, including lung organoids, can be generated. Organoids are applied widely in development, disease modelling, regenerative medicine, and other multiple aspects. Various human pulmonary diseases caused by several factors can be induced and lead to different degrees of lung epithelial injury. Epithelial repair involves the participation of multiple cells and signalling pathways. Lung organoids provide an excellent platform to model injury to and repair of lungs. Here, we review the recent methods of cultivating lung organoids, applications of lung organoids in epithelial repair after injury, and understanding the mechanisms of epithelial repair investigated using lung organoids. By using lung organoids, we can discover the regulatory mechanisms related to the repair of lung epithelia. This strategy could provide new insights for more effective management of lung diseases and the development of new drugs.


Subject(s)
Lung Diseases , Lung Injury , Humans , Lung , Organoids , Regenerative Medicine
17.
J Cell Physiol ; 236(10): 7266-7289, 2021 10.
Article in English | MEDLINE | ID: covidwho-1168883

ABSTRACT

Mesenchymal stem cells (MSCs) are located in various tissues where these cells show niche-dependent multilineage differentiation and secrete immunomodulatory molecules to support numerous physiological processes. Due to their regenerative and reparative properties, MSCs are extremely valuable for cell-based therapy in tackling several pathological conditions including COVID-19. Iron is essential for MSC processes but iron-loading, which is common in several chronic conditions, hinders normal MSC functionality. This not only aggravates disease pathology but can also affect allogeneic and autologous MSC therapy. Thus, understanding MSCs from an iron perspective is of clinical significance. Accordingly, this review highlights the roles of iron and iron-related proteins in MSC physiology. It describes the contribution of iron and endogenous iron-related effectors like hepcidin, ferroportin, transferrin receptor, lactoferrin, lipocalin-2, bone morphogenetic proteins and hypoxia inducible factors in MSC biology. It summarises the excess-iron-induced alterations in MSC components, processes and discusses signalling pathways involving ROS, PI3K/AKT, MAPK, p53, AMPK/MFF/DRP1 and Wnt. Additionally, it evaluates the endogenous and exogenous saviours of MSCs against iron-toxicity. Lastly, it elaborates on the involvement of MSCs in the pathology of clinical conditions of iron-excess, namely, hereditary hemochromatosis, diabetes, ß-thalassaemia and myelodysplastic syndromes. This unique review integrates the distinct fields of iron regulation and MSC physiology. Through an iron-perspective, it describes both mechanistic and clinical aspects of MSCs and proposes an iron-linked MSC-contribution to physiology, pathology and therapeutics. It advances the understanding of MSC biology and may aid in identifying signalling pathways, molecular targets and compounds for formulating adjunctive iron-based therapies for excess-iron conditions, and thereby inform regenerative medicine.


Subject(s)
Iron/metabolism , Mesenchymal Stem Cells/metabolism , Animals , Cell Differentiation/physiology , Cell- and Tissue-Based Therapy/methods , Humans , Immunomodulation/physiology , Mesenchymal Stem Cell Transplantation/methods , Regenerative Medicine/methods , Signal Transduction/physiology
18.
Biochimie ; 185: 9-21, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1126737

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent stem cells. In addition to the capacity for self-renewal and multipotential differentiation, MSCs also have the following characteristics. MSCs can exert immunomodulatory functions through interaction with innate or adaptive immune cells, MSCs with poor immunogenicity can be used for allogeneic transplantation, and MSCs can "home" to inflammation and tumour sites. Based on these biological properties, MSCs demonstrate broad clinical application prospects in the treatment of tissue injury, autoimmune diseases, transplantation, cancer and other inflammation-related diseases. In this review we describe the biological characteristics of MSCs and discuss the research advances of MSCs in regenerative medicine, immunomodulation, oncology, and COVID-19, to fully understand the range of diseases in which MSC therapy may be beneficial.


Subject(s)
COVID-19/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , COVID-19/virology , Cell Differentiation , Clinical Trials as Topic , Humans , Neoplasms/therapy , Regenerative Medicine , SARS-CoV-2/isolation & purification
19.
Stem Cell Res ; 52: 102239, 2021 04.
Article in English | MEDLINE | ID: covidwho-1078188

ABSTRACT

Currently, the world is facing the SARS-CoV-2 pandemic, coronavirus of acute respiratory distress syndrome 2, causes of COVID-19. Coronaviruses are RNA single-stranded viruses that have an envelope. In addition, coronaviruses are classified into four subfamilies: alpha, beta, gamma and delta coronaviruses. The first of them, cause mildly symptomatic or asymptomatic infections, while beta-coronaviruses are responsible for severe diseases. SARS-CoV-2 belongs to the group of beta-coronaviruses. Current available therapies use corticosteroids to reduce inflammation, non-specific antiviral drugs or antibiotics in the treatment of secondary bacterial infections. In addition, therapies based on the use of hydroxychloroquine, chloroquine, remdesvir, ribavirin, interferon or lopinavir-ritonavir were also initially used. Mesenchemical stem cells (MSCs) are widely used in cell therapies, which include both basic research and clinical trials. Their exceptional effectiveness and safety have been confirmed and documented in many clinical studies, which include a number of inflammatory diseases involving the immune system - one of them is systemic lupus erythematosus. Available data indicate the ability to differentiate MSCs and their immunomodulatory effects. In addition, through interactions with immune cells, which include, but are not limited to, macrophages and dendritic cells, or paracrine secretion, MSCs are able to secrete a number of types of cytokines. MSCs are also characterized by tissue regeneration and regulation of inflammation. Due to their properties, researchers turned to determine whether MSC transplantation is able to improve the outcome of patients with COVID-19 viral pneumonia. The presented review provides not only new knowledge in the field of molecular mechanisms of pro-regenerative action of stem cells, but also have the potential to open up new prospects of action to improve lung tissue regeneration in COVID-19 patients. In addition, in review mentioned about clinical trials using MSCs with a complete status, as well as the latest discoveries in molecular biology, a platform model of pluripotent stem cells in the SARS-CoV-2 study on 3D animal models and nanoconjugates based on stem cells.


Subject(s)
COVID-19/therapy , Mesenchymal Stem Cells/cytology , Stem Cell Transplantation , Animals , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Disease Models, Animal , Humans , Immunologic Factors , Inflammation , Pandemics , Regenerative Medicine
20.
Cells ; 10(1)2021 01 11.
Article in English | MEDLINE | ID: covidwho-1067688

ABSTRACT

Under natural conditions, injured cells can be repaired rapidly through inherent biological processes. However, in the case of diabetes, cardiovascular disease, muscular dystrophy, and other degenerative conditions, the natural repair process is impaired. Repair of injury to the cell membrane is an important aspect of physiology. Inadequate membrane repair function is implicated in the pathophysiology of many human disorders. Recent studies show that Mitsugumin 53 (MG53), a TRIM family protein, plays a key role in repairing cell membrane damage and facilitating tissue regeneration. Clarifying the role of MG53 and its molecular mechanism are important for the application of MG53 in regenerative medicine. In this review, we analyze current research dissecting MG53's function in cell membrane repair and tissue regeneration, and highlight the development of recombinant human MG53 protein as a potential therapeutic agent to repair multiple-organ injuries.


Subject(s)
Regenerative Medicine , Tripartite Motif Proteins/metabolism , Animals , Glucose/metabolism , Humans , Phylogeny , Regeneration , Tripartite Motif Proteins/chemistry
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