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1.
Article in Chinese | WPRIM | ID: wpr-880124

ABSTRACT

Mesenchymal stem cells (MSC) are capable of supporting hematopoiesis, regulating immune responses, promoting tissue regeneration and homing to damaged tissues, but their efficacy cannot completely exploit due to various factors. Studies in recent years have shown that the biological characteristics of mesenchymal stem cells have plasticity. Researchers can enhance the biological performance of MSC by pretreatment with hypoxia, bioactive molecules, genetic modification, and mechanical stimulation, as well as adjusting MSC transplantation strategies, which has great significance for promoting the transformation of MSC. Therefore, in this review, the recent research advances in the plasticity of the biological characteristics of MSC are summarized briefly.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Wound Healing
2.
Clinics ; 76: e2604, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249585

ABSTRACT

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.


Subject(s)
Humans , Coronavirus Infections , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Umbilical Cord , Pilot Projects , Betacoronavirus
3.
Article in Chinese | WPRIM | ID: wpr-879288

ABSTRACT

Mesenchymal stem cells (MSCs) are pluripotent stem cells with high self-proliferation and multidirectional differentiation potential. They also have other functions including immune regulation, paracrine and so on, playing an important role in repairing injured tissues. In recent years, a lot of research has been done on how MSCs promote skin injury repair, and a lot of progress has been made. Compared with direct injection of MSCs in the wound area, some special treatments or transplantation methods could enhance the ability of MSCs to repair skin injury. This paper mainly discusses the role of MSCs in skin injury repair and technical ways to improve its repairing capacity, and discusses the existing problems in this field and prospects for future research directions.


Subject(s)
Cell Differentiation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Skin
4.
Medicina (B.Aires) ; 80(6): 696-702, dic. 2020. graf
Article in Spanish | LILACS | ID: biblio-1250293

ABSTRACT

Resumen La terapia celular y la medicina regenerativa son áreas en gran desarrollo en la investigación biomédica. En la mayoría de los tejidos existen mecanismos de auto-reparación llevados a cabo, principalmente, por células madre o progenitoras residentes con capacidad para diferenciarse y reemplazar a las células dañadas o para secretar factores tróficos que induzcan el proceso regenerativo. Dado que estos mecanismos de reparación no siempre son suficientes, se postula que la terapia celular puede contribuir a la regeneración de los tejidos sometidos a injuria. Las células madre/estromales mesenquimales (MSCs, del inglés Mesenchymal Stem/Stromal Cells) son un tipo de progenitor adulto multipotente, que tienen la capacidad de expandirse in vitro con facilidad cuando son aisladas de su nicho in vivo, migrar selectivamente a los tejidos lesionados, modular y evadir el sistema inmunológico, y secretar factores tróficos que ayudan a la reparación tisular. Asimismo, la fácil manipulación ex vivo permitiría también usarlas como vehículos de genes terapéuticos. Las principales fuentes de obtención son la médula ósea, el tejido adiposo y cordón umbilical. Los numerosos estudios pre-clínicos y clínicos han demostrado que las MSCs parecieran ser seguras tanto para uso autólogo como alogénico. En este trabajo se resumen las propiedades de las MSCs y su potencial terapéutico para una amplia gama de enfermedades, también presentamos los distintos ensayos clínicos avanzados que las posicionan en el ámbito biomédico como una herramienta interesante para la regeneración de tejidos y el tratamiento de enfermedades inflamatorias.


Abstract Cell therapy and regenerative medicine are currently active areas for biomedical research. In most tissues, there are self-repair mechanisms carried out mainly by resident stem cells that can differentiate and replace dead cells or secrete trophic factors that stimulate the regenerative process. These mechanisms often fail in degenerative diseases; thus it is postulated that exogenous cell therapy can contribute to tissue regeneration and repair. Mesenchymal stem cells (MSCs) are multipotent adult stem/progenitor cells, which could be easily expanded in vitro and have the ability to selectively migrate toward injured tissues, evade the immune system recognition, and secrete trophic factors to support tissue repair. Furthermore, MSCs could be engineered for the delivery of therapeutic genes. The main sources for MSCs are bone marrow, adipose tissue, and umbilical cord. A number of pre-clinical and clinical studies have shown that MSCs therapy is safe for both autologous and allogeneic uses. This review summarizes information about the properties of MSCs and their therapeutic potential for a broad spectrum of diseases. We also present here the last data about clinical trials that position the use of MSCs as an interesting tool for tissue regeneration and the treatment of inflammatory diseases.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Tissue Engineering , Regenerative Medicine
5.
Int. j. odontostomatol. (Print) ; 14(4): 670-677, dic. 2020.
Article in Spanish | LILACS | ID: biblio-1134556

ABSTRACT

RESUMEN: El tratamiento de dientes inmaduros necróticos es hoy un gran desafío clínico. La ausencia de cierre del ápice y el reducido grosor de las paredes de la dentina hacen que el tratamiento endodóntico del diente sea difícil e impredecible. Tradicionalmente, estos dientes han sido tratados con apexificación y obturación del canal radicular, sin embargo, con este tratamiento el diente permanece desvitalizado y con paredes de dentina frágiles y cortas, lo que compromete su pronóstico. La endodoncia regenerativa, por el contrario, busca revitalizar el diente e inducir una maduración de la raíz, y se basa en la utilización de las células madre mesenquimales presentes en la región periapical, los factores de crecimiento presentes en la dentina y un andamio que permite el crecimiento de tejido nuevo al interior del canal. Los resultados clínicos son alentadores, ya que en general existe maduración de la raíz y revascularización del diente, sin embargo, el tejido neoformado es tejido de tipo reparativo y, a excepción de estudios ocasionales, no se ha observado regeneración de dentina y pulpa. La endodoncia regenerativa se originó para tratar dientes inmaduros necróticos. Sin embargo, recientemente, estudios preliminares han expandido la aplicación de la endodoncia regenerativa a dientes maduros necróticos, es decir, en pacientes adultos. Los resultados clínicos son positivos y similares a los del diente inmaduro, si n embargo, la investigación referente a la revitalización de dientes maduros se encuentra en etapas tempranas y requiere de un mayor nivel de evidencia antes de ser ofrecida sistemáticamente como terapia a pacientes adultos. Los beneficios potenciales justifican mayor investigación al respecto. Este artículo resume la evidencia científica disponible con respecto a la revitalización de dientes inmaduros y maduros necróticos, sus fundamentos biológicos, los resultados esperados y limitaciones, así como el protocolo clínico.


ABSTRACT: Nowadays, the treatment of immature necrotic teeth is an important clinical challenge. The absence of apex closure and low thickness of the dentin walls, make endodontic treatment unpredictable and difficult. Traditionally, these teeth have been treated with apexification and obturation of the root canal. As a result of this treatment, the tooth remains devitalized and with fragile and short dentin walls, which compromises its prognosis. Regenerative endodontics, on the other hand, seeks to revitalize the tooth and induce root maturation, and is based on the use of mesenchymal stem cells present in the periapical tissues, growth factors present in the dentin and a scaffold that allows growth of new tissue in the root ca- nal. The clinical results are encouraging, since generally, there is root maturation and revascularization of the tooth. However, the newly formed tissue is reparative tissue and with the exception of some studies, no regeneration of dentin and pulp has been reported. Regenerative endodontics emerged to treat necrotic immature teeth. However, recently, preliminary studies have applied regenerative endodontics in mature necrotic teeth, in adult patients. Preliminary results are positive and are similar to those of immature teeth. Nevertheless, research regarding the revitalization of mature teeth is in the early stages and requires further evidence before being systematically administered as therapy in adult patients. However, the potential benefits justify further research in this regard. This article summarizes the available scientific evidence regarding the revitalization of immature and mature necrotic teeth, their biological basis, the expected results and limitations, as well as the clinical protocols for each case.


Subject(s)
Humans , Adult , Dental Pulp Necrosis/therapy , Dentition, Permanent , Regenerative Endodontics/methods , Clinical Protocols/standards , Clinical Trials as Topic , Treatment Outcome , Neovascularization, Physiologic , Dental Pulp Necrosis/drug therapy , Mesenchymal Stem Cell Transplantation , Tissue Scaffolds
6.
Int. j. morphol ; 38(5): 1496-1507, oct. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1134467

ABSTRACT

RESUMEN: En la enfermedad hepática crónica el trasplante ortotópico es la única alternativa terapéutica actual pero es limitada por falta de donantes. Ensayos con células madre adultas en daño hepático agudo evidencian promisorios resultados. El objetivo de este trabajo fue evaluar en ratas con daño hepático crónico la efectividad de la infusión de células madre adiposas humanas (CMAd-h). Ratas con fibrosis hepática inducida por tioacetamida fueron agrupadas en: grupo I control que no recibió tioacetamida ni células madre, grupo II recibió tioacetamida y suero fisiológico i.v., grupo III recibió tioacetamida y células madre adiposas 1 x 106/kg i.v. vía vena de la cola. La regeneración hepática histológica se evaluó por el index METAVIR, mientras las Macrophagocytus stellatus, células estrelladas a- SMA+ y células colágeno I+ por inmunohistoquímica; el daño funcional se evaluó por los niveles sanguíneos de los analitos Aspartato Aminotransferasa (AST), Alanina Aminotransferasa (ALT), Fosfatasa Alcalina (ALP), úrea y nitrógeno ureico (BUN) y hemograma. Los resultados muestran atenuación del daño estructural hepático evidenciado por disminución de los nódulos, del grado de lesión histológica en el score Metavir, y disminución de Macrophagocytus stellatus, células a-SMA+ y células colágeno tipo I+; funcionalmente hay reducción moderada de AST, ALT, urea, BUN y disminución moderada de células blancas pero efecto favorable sobre el volumen corpuscular media y la hemoglobina corpuscular media. Ocho semanas después de la infusión hay escasa población de CMAd-h en el hígado. En conclusión la infusión intravenosa de CMAd-h en ratas disminuye el daño funcional y estructural de la fibrosis hepática con escasa persistencia de CMAd-h en el parénquima hepático. A nuestro conocimiento este es el primer trabajo que evalúa el efecto de las CMAd-h en el modelo daño hepático crónico murino y la persistencia de las células trasplantadas.


SUMMARY: In chronic liver disease, orthotopic transplantation is the only current therapeutic alternative but it is limited due to lack of donors. Trials with adult stem cells in acute liver damage show promising results. The aim of this work was to evaluate the effectiveness of human adipose stem cell (h-ASC) infusion in rats with chronic liver damage. Rats with thioacetamide- induced liver fibrosis were grouped into: group I control that did not receive thioacetamide and h-ASC, group II received thioacetamide and saline i.v., group III received thioacetamide and h-ASC 1 x 106/ kg i.v. via tail vein. Histological liver regeneration was evaluated by METAVIR index, while Macrophagocytus stellatus (Kupffer cells), stellate cells a-SMA+ and collagen I+ cells by immunohistochemistry; functional damage was evaluated by blood levels of the analytes Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Urea and Blood Urea Nitrogen (BUN) and hemogram. The results show attenuation of structural liver damage evidenced by decreased nodules, degree of histologic injury on Metavir score, and decreased Macrophagocytus stellatus, a-SMA+ cells and type I+ collagen cells; functionally there is moderate reduction of AST, ALT, urea, BUN and moderate decrease of white cells but favorable effect on mean corpuscular volume and mean corpuscular hemoglobin. Eight weeks after infusion there is a small population of h-ASC in the liver. In conclusion, intravenous infusion of h-ASC in rats reduces functional and structural damage of hepatic fibrosis with low persistence of h- ASC in the liver parenchyma. To our knowledge this is the first work that evaluates the effect of h-SC in the model of chronic murine liver damage and the persistence of transplanted cells.


Subject(s)
Animals , Female , Rats , Mesenchymal Stem Cell Transplantation/methods , Liver Cirrhosis, Experimental/therapy , Aspartate Aminotransferases/analysis , Immunohistochemistry , Treatment Outcome , Alanine Transaminase/analysis , Disease Models, Animal , Alkaline Phosphatase/analysis , Cell- and Tissue-Based Therapy/methods , Liver Cirrhosis, Experimental/pathology
7.
Rev. Hosp. Ital. B. Aires (2004) ; 40(3): 105-116, sept. 2020. ilus, tab
Article in Spanish | LILACS | ID: biblio-1129064

ABSTRACT

Este trabajo tiene como objetivo revisar las contribuciones de la biotecnología, en relación con el tratamiento, diagnóstico y la monitorización de la enfermedad renal crónica (ERC) y sus comorbilidades más frecuentes, especialmente la anemia. En relación con los tratamientos, enfocamos el desarrollo de productos biofarmacéuticos como los agentes estimulantes de la eritropoyesis (ESA), que fueron los primeros biofármacos utilizados para el tratamiento de la anemia asociada a la ERC; analizamos sus características y utilización actual después de varios años de experiencia clínica, así como también otras alternativas en desarrollo. Revisamos distintos tipos de bioterapias, la utilización de las células estromales mesenquimales de médula ósea (MSC) y tratamientos alternativos con modificaciones dietarias, que se basan en la asociación entre la microbiota intestinal de los pacientes renales crónicos y sus condiciones fisiopatológicas. Finalmente, en relación con el diagnóstico y monitorización, nos referimos al estudio y validación de biomarcadores diagnósticos, predictivos y terapéuticos que han permitido optimizar los resultados clínicos en este tipo de pacientes. (AU)


The aim of this work is to review the contributions of biotechnology, in relation to the treatment, diagnosis and monitoring of chronic kidney disease (CKD) and its most frequent comorbidities, especially anemia. Regarding the treatment, we focus on the development of biopharmaceutical products such as erythropoiesis stimulating agents (ESA), which were the first biopharmaceuticals used to treat anemia associated with chronic kidney disease (CKD). We analyzed their characteristics and their current use after several years of clinical experience, as well as other alternatives in development. We also review different types of biotherapies, the use of bone marrow mesenchymal stromal cells (MSC) and alternative treatments with dietary modifications, which are based on the association between the intestinal microbiota of chronic kidney patients and their pathophysiological conditions. Finally, in relation to diagnosis and monitoring, we refer to the study and validation of diagnostic, predictive and therapeutic biomarkers that have made clinical results possible to be optimized in this type of patient. (AU)


Subject(s)
Humans , Biological Therapy/trends , Renal Insufficiency, Chronic/therapy , Quality of Life , Biotechnology , Biomarkers , Erythropoietin/deficiency , Probiotics/therapeutic use , Mesenchymal Stem Cell Transplantation/trends , Erythropoiesis/drug effects , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/diet therapy , Renal Insufficiency, Chronic/rehabilitation , Prebiotics/classification , Glycoside Hydrolase Inhibitors/therapeutic use , Gastrointestinal Microbiome , Hematinics/administration & dosage , Hematinics/pharmacology , Hematinics/pharmacokinetics , Anemia/diagnosis , Anemia/etiology , Anemia/drug therapy
8.
Medicina (B.Aires) ; 80(supl.2): 2-6, mar. 2020. ilus
Article in Spanish | LILACS | ID: biblio-1125097

ABSTRACT

Los trastornos heredados del metabolismo son enfermedades graves de la infancia que cursan con un gran deterioro cognitivo y del desarrollo psicomotor. La fisiopatología del progresivo deterioro del sistema nervioso suele estar asociada a una severa neuroinflamación y desmielinización, y como consecuencia, neurodegeneración. Por el momento no tienen cura y precisan de actitudes terapéuticas precoces y agresivas, que conllevan altas tasas de mortalidad y, muy frecuentemente, escasos grados de mejoría funcional y supervivencia. El trasplante de médula ósea y de células mesenquimales de médula ósea son terapias de elección y experimentales que consiguen mejorar el curso de estas enfermedades mediante diferentes mecanismos de acción: remplazo de enzima deficiente, intercambio de membranas y regulación del proceso inflamatorio.


Inherited metabolism disorders are serious childhood diseases that lead to significant cognitive impairment and regression of psychomotor development. The pathophysiology of the neural progressive deterioration is usually associated with severe neuroinflammation and demyelination, and as a consequence, neurodegeneration. At the moment they have no adequate treatment and require early and aggressive therapeutic approaches, which entail high mortality rates and, very frequently, low degrees of functional improvement and survival. Bone marrow transplantation and bone marrow mesenchymal cells grafts are therapeutic and experimental therapies that improve the course of these diseases through different mechanisms of action: enzyme replacement, membrane exchange and regulation of the inflammatory process.


Subject(s)
Humans , Bone Marrow Transplantation/methods , Lysosomal Storage Diseases/therapy , Peroxisomal Disorders/therapy , Lysosomal Storage Diseases/physiopathology , Peroxisomal Disorders/physiopathology , Mesenchymal Stem Cell Transplantation/methods
9.
Protein & Cell ; (12): 707-722, 2020.
Article in English | WPRIM | ID: wpr-828750

ABSTRACT

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.


Subject(s)
Adoptive Transfer , Alveolar Epithelial Cells , Pathology , Animals , Apoptosis , Betacoronavirus , Body Fluids , Metabolism , CD4-Positive T-Lymphocytes , Allergy and Immunology , Clinical Trials as Topic , Coinfection , Therapeutics , Coronavirus Infections , Allergy and Immunology , Disease Models, Animal , Endothelial Cells , Pathology , Extracorporeal Membrane Oxygenation , Genetic Therapy , Methods , Genetic Vectors , Therapeutic Uses , Humans , Immunity, Innate , Inflammation Mediators , Metabolism , Lung , Pathology , Mesenchymal Stem Cell Transplantation , Methods , Mesenchymal Stem Cells , Physiology , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Allergy and Immunology , Respiratory Distress Syndrome , Allergy and Immunology , Pathology , Therapeutics , Translational Medical Research
10.
Protein & Cell ; (12): 707-722, 2020.
Article in English | WPRIM | ID: wpr-828586

ABSTRACT

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.


Subject(s)
Adoptive Transfer , Alveolar Epithelial Cells , Pathology , Animals , Apoptosis , Betacoronavirus , Body Fluids , Metabolism , CD4-Positive T-Lymphocytes , Allergy and Immunology , Clinical Trials as Topic , Coinfection , Therapeutics , Coronavirus Infections , Allergy and Immunology , Disease Models, Animal , Endothelial Cells , Pathology , Extracorporeal Membrane Oxygenation , Genetic Therapy , Methods , Genetic Vectors , Therapeutic Uses , Humans , Immunity, Innate , Inflammation Mediators , Metabolism , Lung , Pathology , Mesenchymal Stem Cell Transplantation , Methods , Mesenchymal Stem Cells , Physiology , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Allergy and Immunology , Respiratory Distress Syndrome , Allergy and Immunology , Pathology , Therapeutics , Translational Medical Research
11.
Article in Chinese | WPRIM | ID: wpr-878674

ABSTRACT

Objective To investigate the therapeutic effect of SPK1 gene transfected adipose derived mesenchymal stem cells(ADMSC)on experimental autoimmune encephalomyelitis mice and the effect on T helper cell 17(Th17)/regulatory T(Treg) cells balance. Methods EAE was induced by myelin oligodendrocyte glycoprotein 35-55 in mice.Totally 44 mice were randomly divided into four groups:normal control group(NC group),model group(EAE group),ADMSC group,and ADMSC-SPK1 group.Forty days after injection,the pathological changes of brain and spinal cord,Th17/Treg-related inflammatory markers in brain tissue,expressions of interleukin-17A(IL-17A)and forkhead box protein p3(Foxp3)in brain and spinal cord tissue,and flow cytometric results of spleen immune cells were detected. Results Forty days after the injection,serious inflammatory cell infiltration and demyelination occurred in the brain and spinal cord of EAE group,whereas demyelination and axonal injury were improved in ADMSC group and ADMSC-SPK1 group.Compared with EAE group,the ADMSC group and ADMSC-SPK1 group had significantly improved levels of IL-17A(


Subject(s)
Adipose Tissue/cytology , Animals , Cytokines , Encephalomyelitis, Autoimmune, Experimental/therapy , Interleukin-17 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Mice , Mice, Inbred C57BL , Phosphotransferases (Alcohol Group Acceptor)/genetics , T-Lymphocytes, Regulatory/cytology , Th17 Cells/cytology , Transfection
12.
Chinese Journal of Biotechnology ; (12): 1979-1991, 2020.
Article in Chinese | WPRIM | ID: wpr-878459

ABSTRACT

Coronavirus disease 2019 (COVID-19) has spread widely on a large scale in the whole world at present, seriously endangering human health. There are still no effective and specific drugs, so it is urgent to find safe and effective therapeutic methods. Mesenchymal stem cells (MSCs) have many biological functions of powerful immunomodulation and tissue repair and regeneration. As a stem cell therapy, it has the potential to reduce the tissue injury and mortality in severe patients infected with novel coronavirus. At present, many research institutions in China and abroad have started a number of clinical research projects about MSCs in the treatment of COVID-19. In addition, those projects have initially confirmed the safety and effectiveness of this therapy. Therefore, this research field has been proved to have a very good clinical therapy prospect.


Subject(s)
Betacoronavirus , COVID-19 , China , Coronavirus Infections/therapy , Humans , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Pandemics , Pneumonia, Viral/therapy , SARS-CoV-2
13.
Chinese Journal of Biotechnology ; (12): 1970-1978, 2020.
Article in Chinese | WPRIM | ID: wpr-878458

ABSTRACT

At present, SARS-CoV-2 is raging, and novel coronavirus pneumonia (COVID-19) has caused more than 35 million confirmed patients and more than 500 000 cases death, which seriously endanger human health, socioeconomic development, as well as global medical and public health systems. COVID-19 is highly contagious, has a long incubation period, and causes many death cases due to lack of effective specific treatment. Mesenchymal stem cells have powerful anti-inflammatory and immunoregulatory functions, and can effectively reduce the cytokine storm caused by coronavirus in patients, and improve the pulmonary fibrosis of patients, promote the repair of damaged lung tissue, and reduce the mortality. Currently, a number of related clinical trials of mesenchymal stem cell treatment of COVID-19 have been conducted, and have confirmed the safety and efficacy, suggesting a good clinical application prospect. While progress has been made in mesenchymal stem cell therapy for COVID-19, we should also catch sight of the problems and challenges faced by mesenchymal stem cell clinical trials under severe epidemic situation, including clinical trials design, stem cell quality management, and ethics in treatment. Only by paying attention to these can we guarantee the safe and effective development of mesenchymal stem cell clinical trials in the treatment of COVID-19.


Subject(s)
Betacoronavirus , COVID-19 , Clinical Trials as Topic , Coronavirus Infections/therapy , Humans , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Pandemics , Pneumonia, Viral/therapy , SARS-CoV-2
14.
Journal of Experimental Hematology ; (6): 1019-1024, 2020.
Article in Chinese | WPRIM | ID: wpr-827168

ABSTRACT

OBJECTIVE@#To investigate the effects of combined infusion of mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) on lung injury after hematopoietic stem cell transplantation (HSCT).@*METHODS@#The experiment was divided into normal control group, irradiation group, bone marrow cell transplantation group (BMT group), BMT+EPC group, BMT+MSC group and BMT+EPC+MSC group. The model of HSCT was established, on the 30th day after transplantation, the mice were sacrificed. Then lung tissue was taken for testing. The mRNA expression levels of VEGF, IL-18, IL-12b were detected by RT-PCR, and protein expression level of NLRP3 was detected by Western blot. The expression of MPO and CD146 was observed by immunohistochemistry assay.@*RESULTS@#The expression level of VEGF gene in BMT+EPC+MSC group was significantly higher than that in other groups (P<0.01). The expression level of IL-18 and IL-12b gene was the highest in BMT group and the lowest in BMT+EPC+MSC group, and the difference was statistically significant (P<0.05). HSCT could increase the expression of NLRP3 protein, and the BMT+EPC+MSC could significantly reduce the level of NLRP3 protein in lung cells, tending to normal. Compared with normal tissues, the BMT+EPC+MSC could improve the lung tissue structure more effectively, the expression of MPO positive cells was lower, and the expression of VEGF positive cells was higher.@*CONCLUSIONS@#The combined infusion of MSC and EPC can promote capillary regeneration, alleviate inflammation and promote lung repair after HSCT, which is superior to single EPC or MSC infusion.


Subject(s)
Animals , Endothelial Progenitor Cells , Hematopoietic Stem Cell Transplantation , Lung Injury , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Mice , Mice, Inbred C57BL
15.
Acta Physiologica Sinica ; (6): 426-432, 2020.
Article in Chinese | WPRIM | ID: wpr-827045

ABSTRACT

The purpose of the present study was to investigate the effects of forkhead box O4 (FOXO4) on the senescence of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The hUC-MSCs were induced to senescence by natural passage, and FOXO4 expression was inhibited by lentiviral shRNA transfection. The hallmark of cell senescence was analyzed by β-galactosidase staining, and the cell viability was assayed by CCK-8 method. Flow cytometry was used to investigate the apoptosis of hUC-MSCs. The expression levels of Bcl-2, Bax, FOXO4, interleukin 6 (IL-6) and cleaved Caspase-3 were detected by qPCR and Western blot. Immunofluorescence staining was used to detect FOXO4 expression. The amount of IL-6 secreted by hUC-MSCs was detected by ELISA. The results showed that, compared with the passage 1, senescent hUC-MSCs showed up-regulated expression levels of Bax and FOXO4, down-regulated expression levels of Bcl-2 and cleaved Caspase-3, and increased IL-6 mRNA expression and secretion. FOXO4 inhibition in senescent hUC-MSCs promoted cell apoptosis, reduced cell viability, and inhibited the mRNA expression and secretion of IL-6. These results suggest that FOXO4 maintains viability and function of senescent hUC-MSCs by repressing their apoptosis response, thus accelerating senescence of the whole cell colony.


Subject(s)
Apoptosis , Cell Cycle Proteins , Cell Survival , Cellular Senescence , Forkhead Transcription Factors , Humans , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Transcription Factors , Umbilical Cord
16.
Protein & Cell ; (12): 707-722, 2020.
Article in English | WPRIM | ID: wpr-827023

ABSTRACT

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.


Subject(s)
Adoptive Transfer , Alveolar Epithelial Cells , Pathology , Animals , Apoptosis , Betacoronavirus , Body Fluids , Metabolism , CD4-Positive T-Lymphocytes , Allergy and Immunology , Clinical Trials as Topic , Coinfection , Therapeutics , Coronavirus Infections , Allergy and Immunology , Disease Models, Animal , Endothelial Cells , Pathology , Extracorporeal Membrane Oxygenation , Genetic Therapy , Methods , Genetic Vectors , Therapeutic Uses , Humans , Immunity, Innate , Inflammation Mediators , Metabolism , Lung , Pathology , Mesenchymal Stem Cell Transplantation , Methods , Mesenchymal Stem Cells , Physiology , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Allergy and Immunology , Respiratory Distress Syndrome , Allergy and Immunology , Pathology , Therapeutics , Translational Medical Research
17.
Clinics ; 75: e1656, 2020. graf
Article in English | LILACS | ID: biblio-1133444

ABSTRACT

OBJECTIVES: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism. METHODS: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated. CONCLUSION: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet β-cells and decrease in pro-inflammatory cytokines and apoptosis of islets.


Subject(s)
Humans , Animals , Male , Mice , Rats , Mesenchymal Stem Cell Transplantation , Diabetes Mellitus, Experimental/therapy , Diabetes Mellitus, Type 2/therapy , Insulin-Secreting Cells , Hyperbaric Oxygenation/methods , Stem Cells , Tooth, Deciduous , China , Rats, Sprague-Dawley , Diabetes Mellitus, Type 2/chemically induced , Mesenchymal Stem Cells , Insulin
18.
Rev. Assoc. Med. Bras. (1992) ; 66(supl.1): s45-s54, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057110

ABSTRACT

SUMMARY INTRODUCTION: Acute kidney injury (AKI) is highly prevalent today. It has a multifactorial aetiology and affects people of all ages, genders and ethnicities. Its treatment is essentially supportive of renal function substitution, so new treatment alternatives such as mesenchymal stem cell therapy (MSCs) should be investigated. METHODS: This review encompasses our understanding of the main mechanisms of action of MSCs in preclinical models of AKI by renal pedicle clamping ischemia-reperfusion, chemotherapy (cisplatin) and kidney transplantation in small and large animals, as well as outcomes in patients with AKI due to ischemia and kidney transplantation. RESULTS: Cellular therapy with MSCs has benefits in preclinical studies of AKI through various mechanisms, such as anti-inflammatory, antiapoptotic, oxidative anti-stress, antifibrotic, immunomodulatory and proangiogenic. In humans, MSC therapy is safe and effective. However, the challenges of MSC cell therapy include investigating protocols about the optimal dose of these cells, the route and frequency of appropriate administration, and the design of further biodistribution studies over a long follow-up period. In addition, a better understanding of molecular signalling and cellular interactions in the microenvironment of each organ and tissue is needed in order to define the best time to administer MSCs. Another challenge would be to mitigate the heterogeneity of the profile of cultured MSCs through preconditioning approaches. CONCLUSIONS: Cellular therapy with MSCs is very promising and should be part of the treatment of AKI patients in combination with other approaches already available, helping to accelerate recovery and/or slow the progression to chronic kidney disease. Randomized, multicentre controlled studies are needed to develop robust protocols that validate population-based cell therapy with MSCs.


Subject(s)
Humans , Animals , Mesenchymal Stem Cell Transplantation/trends , Acute Kidney Injury/therapy , Mesenchymal Stem Cells , Kidney/physiopathology , Tissue Distribution , Mesenchymal Stem Cell Transplantation/methods
20.
Arq. bras. oftalmol ; 82(1): 32-37, Jan.-Feb. 2019. graf
Article in English | LILACS | ID: biblio-973879

ABSTRACT

ABSTRACT Purpose: To evaluate the ability of human immature dental pulp stem cells, which are mesenchymal stem cells of neural crest origin, to differentiate into the corneal epithelium for purposes of corneal transplantation and tissue engineering when cultured on de-epithelized amniotic membranes. Methods: We compared the immunophenotypes (ABCG2, K3/12, and vimentin) of cells grown on amniotic membranes or plastic surfaces under serum-free conditions or in culture media containing serum or serum replacement components. Results: Immature dental pulp stem cells grown on amniotic membranes under basal conditions are able to maintain their undifferentiated state. Our data also suggest that the culture medium used in the present work can modulate the expression of immature dental pulp stem cell markers, thus inducing epithelial differentiation of these cells in vitro. Conclusions: Our results suggest that the amniotic membrane is a good choice for the growth and transplantation of mesenchymal stem cells, particularly immature dental pulp stem cells, in clinical ocular surface reconstruction.


RESUMO Objetivos: Avaliar a capacidade das células-tronco imaturas da polpa do dente de leite que são células-tronco mesenquimais de origem da crista neural, de se diferenciarem no epitélio corneano para fins de transplante de córnea e engenharia de tecidos quando cultivadas em membrana amnióticas desepitelizadas. Métodos: Foram comparamos so imunofenótipo (ABCG2, CK3/12 e vimentina) de células cultivadas em membranas amnióticas ou em superfícies plásticas sob condições livres de soro ou em meios de cultura contendo soro ou componentes de substituição de soro. Resultados: Células-tronco imaturas da polpa do dente de leite cultivadas sobre membrana amniótica em condições basais são capazes de manter seu estado indiferenciado. Nossos dados também sugerem que o meio de cultura utilizado no presente trabalho pode modular a expressão de marcadores de células-tronco imaturas da polpa do dente de leite, induzindo a diferenciação epitelial destas células in vitro. Conclusão: Nossos resultados sugerem que a membrana amniótica é uma boa escolha para o crescimento e transplante de células-tronco mesenquimais, particularmente as células-tronco imaturas da polpa do dente de leite, na reconstrução da superfície ocular.


Subject(s)
Humans , Epithelium, Corneal/transplantation , Dental Pulp/cytology , Mesenchymal Stem Cell Transplantation/methods , Tissue Scaffolds , Mesenchymal Stem Cells/cytology , Amnion , Time Factors , Cells, Cultured , Reproducibility of Results , Fluorescent Antibody Technique , Cell Culture Techniques/methods , Corneal Diseases/surgery , Cell Proliferation
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