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3.
Cells ; 9(9)2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887260

RESUMO

We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients' respiratory capacity and increase the expectations of their cure.


Assuntos
Raios gama , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos da radiação , Síndrome do Desconforto Respiratório do Adulto/terapia , Anexina A1/metabolismo , Betacoronavirus/isolamento & purificação , Ensaios Clínicos como Assunto , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Exossomos/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pandemias , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/virologia
4.
Clin Dermatol ; 38(4): 494-496, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972609

RESUMO

Stem cells have recently garnered increased attention, especially pertaining to their use in cutaneous rejuvenation. Their popularity has continued to grow with patients and consumers alike, which has followed the substantial marketing bolstering them. Although limited, studies have begun to demonstrate promise in the field of esthetics. We review the prominent studies in the literature to shed more light on the use of stem cells for cosmetic practitioners.


Assuntos
Técnicas Cosméticas , Dermatologia , Estética , Células-Tronco Mesenquimais/citologia , Rejuvenescimento/fisiologia , Envelhecimento da Pele , Fenômenos Fisiológicos da Pele , Células-Tronco , Tecido Adiposo/citologia , Células da Medula Óssea , Diferenciação Celular , Autorrenovação Celular , Humanos , Pele , Células-Tronco/fisiologia
5.
J Int Med Res ; 48(9): 300060520955063, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32972277

RESUMO

At the end of 2019, novel coronavirus (COVID-19) infection was detected in Wuhan City, Hubei Province, China. The COVID-19 infection characteristics include a long incubation period, strong infectivity, and high fatality rate, and it negatively affects human health and social development. COVID-19 has become a common problem in the global medical and health system. It is essentially an acute self-limiting disease. Patients with severe COVID-19 infection usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death within a short period after onset. There remains a lack of effective drugs for such patients clinically. Mesenchymal stem cells (MSCs) are expected to reduce the risk of complications and death in patients because they have strong anti-inflammatory and immunomodulatory capabilities, which can improve the microenvironment, promote neovascularization, and enhance tissue repair capabilities. China is currently conducting several clinical trials on MSCs for the treatment of COVID-19. Here, we review the research progress related to using stem cells to treat patients with COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Pneumonia Viral/terapia , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/virologia , Prognóstico
6.
Anticancer Res ; 40(10): 5641-5647, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988888

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have gained remarkable attention because of their ability to dualistically regulate tumor growth. The main objective of this study was to evaluate the apoptotic effects of human bone marrow-derived (hBM) MSCs in combination with interferon gamma (IFN-γ) on MCF-7 breast cancer cells, and to determine the cytokines involved in the apoptotic process. MATERIALS AND METHODS: hBM-MSCs were co-cultured with MCF-7 cells either directly and indirectly for 72 h in-vitro. Levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), apoptosis and cytokines were analyzed. RESULTS: hBM-MSCs increased the apoptosis of MCF-7 cells partially through TRAIL in vitro. IFN-γ enhanced the apoptotic effect of hBM-MSCs (p<0.001). CONCLUSION: hBM-MSCs in combination with IFN-γ might be a suitable therapy for breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Interferon gama/farmacologia , Células-Tronco Mesenquimais/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/genética , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Técnicas de Cocultura , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interferon gama/genética , Células MCF-7 , Células-Tronco Mesenquimais/citologia
7.
Cells ; 9(9)2020 09 02.
Artigo em Inglês | MEDLINE | ID: covidwho-742752

RESUMO

We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients' respiratory capacity and increase the expectations of their cure.


Assuntos
Raios gama , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos da radiação , Síndrome do Desconforto Respiratório do Adulto/terapia , Anexina A1/metabolismo , Betacoronavirus/isolamento & purificação , Ensaios Clínicos como Assunto , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Exossomos/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pandemias , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/virologia
9.
Cell Transplant ; 29: 963689720952089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32830527

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, originating from Wuhan, China, is known to cause severe acute respiratory symptoms. The occurrence of a cytokine storm in the lungs is a critical step in the disease pathogenesis, as it causes pathological lesions, pulmonary edema, and acute respiratory distress syndrome, potentially resulting in death. Currently, there is no effective treatment that targets the cytokine storm and helps regenerate the damaged tissue. Mesenchymal stem cells (MSCs) are known to act as anti-inflammatory/immunomodulatory candidates and activate endogenous regeneration. As a result, MSC therapy is a potential treatment approach for COVID-19. Intravenous injection of clinical-grade MSCs into COVID-19 patients can induce an immunomodulatory response along with improved lung function. Dental pulp stem cells (DPSCs) are considered a potential source of MSCs for immunomodulation, tissue regeneration, and clinical application. Although some current clinical trials have treated COVID-19 patients with DPSCs, this therapy has not been approved. Here, we review the potential use of DPSCs and their significance in the development of a therapy for COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Polpa Dentária/citologia , Imunomodulação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Pneumonia Viral/terapia , Betacoronavirus/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Polpa Dentária/imunologia , Humanos , Imunoterapia/métodos , Inflamação/imunologia , Inflamação/terapia , Pulmão/imunologia , Pulmão/fisiologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/terapia , Células-Tronco Mesenquimais/citologia , Pandemias , Pneumonia Viral/imunologia , Regeneração
10.
Int J Nanomedicine ; 15: 5825-5838, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821104

RESUMO

Background and Purpose: The extracellular matrix (ECM) derived from bone marrow mesenchymal stem cells (BMSCs) has been used in regenerative medicine because of its good biological activity; however, its poor mechanical properties limit its application in bone regeneration. The purpose of this study is to construct a three dimensional-printed hydroxyapatite (3D-HA)/BMSC-ECM composite scaffold that not only has biological activity but also sufficient mechanical strength and reasonably distributed spatial structure. Methods: A BMSC-ECM was first extracted and formed into micron-sized particles, and then the ECM particles were modified onto the surface of 3D-HA scaffolds using an innovative linking method to generate composite 3D-HA/BMSC-ECM scaffolds. The 3D-HA scaffolds were used as the control group. The basic properties, biocompatibility and osteogenesis ability of both scaffolds were tested in vitro. Finally, a critical skull defect rat model was created and the osteogenesis effect of the scaffolds was evaluated in vivo. Results: The compressive modulus of the composite scaffolds reached 9.45±0.32 MPa, which was similar to that of the 3D-HA scaffolds (p>0.05). The pore size of the two scaffolds was 305±47 um and 315±34 um (p>0.05), respectively. A CCK-8 assay indicated that the scaffolds did not have cytotoxicity. The composite scaffolds had good cell adhesion ability, with a cell adhesion rate of up to 76.00±6.17% after culturing for 7 hours, while that of the 3D-HA scaffolds was 51.85±4.77% (p<0.01). In addition, the composite scaffold displayed higher alkaline phosphatase (ALP) activity, osteogenesis-related mRNA expression, and calcium nodule formation, thus confirming that the composite scaffolds had good osteogenic activity. The composite scaffolds exhibited good bone repair in vivo and were superior to the 3D-HA scaffolds. Conclusion: We conclude that BMSC-ECM is a good osteogenic material and that the composite scaffolds have good osteogenic ability, which provides a new method and concept for the repair of bone defects.


Assuntos
Durapatita/farmacologia , Matriz Extracelular/metabolismo , Células-Tronco Mesenquimais/citologia , Tecidos Suporte/química , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Adesão Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Hidrodinâmica , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/ultraestrutura , Osteogênese/efeitos dos fármacos , Osteogênese/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
11.
Small ; 16(38): e2003010, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32815251

RESUMO

Currently, mesenchymal stem cells (MSCs)-based therapies for bone regeneration and treatments have gained significant attention in clinical research. Though many chemical and physical cues which influence the osteogenic differentiation of MSCs have been explored, scaffolds combining the benefits of Zn2+ ions and unique nanostructures may become an ideal interface to enhance osteogenic and anti-infective capabilities simultaneously. In this work, motivated by the enormous advantages of Zn-based metal-organic framework-derived nanocarbons, C-ZnO nanocarbons-modified fibrous scaffolds for stem cell-based osteogenic differentiation are constructed. The modified scaffolds show enhanced expression of alkaline phosphatase, bone sialoprotein, vinculin, and a larger cell spreading area. Meanwhile, the caging of ZnO nanoparticles can allow the slow release of Zn2+ ions, which not only activate various signaling pathways to guide osteogenic differentiation but also prevent the potential bacterial infection of implantable scaffolds. Overall, this study may provide new insight for designing stem cell-based nanostructured fibrous scaffolds with simultaneously enhanced osteogenic and anti-infective capabilities.


Assuntos
Carbono/química , Células-Tronco Mesenquimais/citologia , Nanofibras/química , Osteogênese/fisiologia , Tecidos Suporte/química , Óxido de Zinco/química , Fosfatase Alcalina/metabolismo , Diferenciação Celular/fisiologia , Células Cultivadas , Humanos , Sialoproteína de Ligação à Integrina/metabolismo , Teste de Materiais , Células-Tronco Mesenquimais/metabolismo , Microscopia Eletrônica de Varredura , Nanofibras/ultraestrutura , Transdução de Sinais , Engenharia Tecidual , Vinculina/metabolismo
12.
Nature ; 584(7822): 535-546, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32848221

RESUMO

Substantial research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, affects fundamental cellular processes, including spreading, growth, proliferation, migration, differentiation and organoid formation. Linearly elastic polyacrylamide hydrogels and polydimethylsiloxane (PDMS) elastomers coated with ECM proteins are widely used to assess the role of stiffness, and results from such experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo. However, tissues and ECMs are not linearly elastic materials-they exhibit far more complex mechanical behaviours, including viscoelasticity (a time-dependent response to loading or deformation), as well as mechanical plasticity and nonlinear elasticity. Here we review the complex mechanical behaviours of tissues and ECMs, discuss the effect of ECM viscoelasticity on cells, and describe the potential use of viscoelastic biomaterials in regenerative medicine. Recent work has revealed that matrix viscoelasticity regulates these same fundamental cell processes, and can promote behaviours that are not observed with elastic hydrogels in both two- and three-dimensional culture microenvironments. These findings have provided insights into cell-matrix interactions and how these interactions differentially modulate mechano-sensitive molecular pathways in cells. Moreover, these results suggest design guidelines for the next generation of biomaterials, with the goal of matching tissue and ECM mechanics for in vitro tissue models and applications in regenerative medicine.


Assuntos
Elasticidade , Matriz Extracelular/metabolismo , Substâncias Viscoelásticas , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Técnicas de Cultura de Células , Forma Celular , Matriz Extracelular/química , Humanos , Mecanotransdução Celular , Células-Tronco Mesenquimais/citologia , Modelos Biológicos , Medicina Regenerativa
13.
PLoS One ; 15(8): e0237479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790806

RESUMO

OBJECTIVE: As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors. DESIGN: Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box (SOX) 9, transforming growth factor beta (TGFB) 1 or bone morphogenetic protein (BMP) 2 cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP. The respective constructs were analyzed histologically, immunohistochemically, biochemically, and by qRT-PCR for chondrogenesis and hypertrophy. RESULTS: Chondrogenesis in MSCs was consistently and strongly induced in collagen I hydrogels by the transgenes SOX9, TGFB1 and BMP2 as evidenced by positive staining for proteoglycans, chondroitin-4-sulfate (CS4) and collagen (COL) type II, increased levels of glycosaminoglycan (GAG) synthesis, and expression of mRNAs associated with chondrogenesis. The control groups were entirely non-chondrogenic. The levels of hypertrophy, as judged by expression of alkaline phosphatase (ALP) and COL X on both the protein and mRNA levels revealed different stages of hypertrophy within the chondrogenic groups (BMP2>TGFB1>SOX9). CONCLUSIONS: Different types of neocartilage with varying levels of hypertrophy could be generated from human MSCs in collagen hydrogels by transfer of genes encoding the chondrogenic factors SOX9, TGFB1 and BMP2. This technology may be harnessed for regeneration of specific zones of native cartilage upon damage.


Assuntos
Proteína Morfogenética Óssea 2/genética , Hidrogéis/química , Fatores de Transcrição SOX9/genética , Fator de Crescimento Transformador beta1/genética , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Cartilagem/citologia , Cartilagem/metabolismo , Cartilagem/patologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Condrogênese/genética , Colágeno Tipo I/química , Colágeno Tipo X/genética , Meios de Cultura Livres de Soro/química , Glicosaminoglicanos/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , RNA Mensageiro/metabolismo , Fatores de Transcrição SOX9/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
14.
BMB Rep ; 53(8): 400-412, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32731913

RESUMO

The world has witnessed unimaginable damage from the coronavirus disease-19 (COVID-19) pandemic. Because the pandemic is growing rapidly, it is important to consider diverse treatment options to effectively treat people worldwide. Since the immune system is at the hub of the infection, it is essential to regulate the dynamic balance in order to prevent the overexaggerated immune responses that subsequently result in multiorgan damage. The use of stem cells as treatment options has gained tremendous momentum in the past decade. The revolutionary measures in science have brought to the world mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exo) as therapeutic opportunities for various diseases. The MSCs and MSCExos have immunomodulatory functions; they can be used as therapy to strike a balance in the immune cells of patients with COVID-19. In this review, we discuss the basics of the cytokine storm in COVID-19, MSCs, and MSC-derived exosomes and the potential and stem-cell-based ongoing clinical trials for COVID-19. [BMB Reports 2020; 53(8): 400-412].


Assuntos
Infecções por Coronavirus/terapia , Exossomos/transplante , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Sistema Imunitário/metabolismo , Imunomodulação , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia
15.
Nat Commun ; 11(1): 3955, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769998

RESUMO

Cellular therapy to treat heart failure is an ongoing focus of intense research, but progress toward structural and functional recovery remains modest. Engineered augmentation of established cellular effectors overcomes impediments to enhance reparative activity. Such 'next generation' implementation includes delivery of combinatorial cell populations exerting synergistic effects. Concurrent isolation and expansion of three distinct cardiac-derived interstitial cell types from human heart tissue, previously reported by our group, prompted design of a 3D structure that maximizes cellular interaction, allows for defined cell ratios, controls size, enables injectability, and minimizes cell loss. Herein, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and c-Kit+ cardiac interstitial cells (cCICs) when cultured together spontaneously form scaffold-free 3D microenvironments termed CardioClusters. scRNA-Seq profiling reveals CardioCluster expression of stem cell-relevant factors, adhesion/extracellular-matrix molecules, and cytokines, while maintaining a more native transcriptome similar to endogenous cardiac cells. CardioCluster intramyocardial delivery improves cell retention and capillary density with preservation of cardiomyocyte size and long-term cardiac function in a murine infarction model followed 20 weeks. CardioCluster utilization in this preclinical setting establish fundamental insights, laying the framework for optimization in cell-based therapeutics intended to mitigate cardiomyopathic damage.


Assuntos
Microambiente Celular , Miocárdio/patologia , Cicatrização , Animais , Animais Recém-Nascidos , Capilares/patologia , Agregação Celular , Morte Celular , Linhagem da Célula , Tamanho Celular , Citoproteção , Células Progenitoras Endoteliais/citologia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Recém-Nascido , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos NOD , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/citologia , Estresse Oxidativo , Comunicação Parácrina , Ratos Sprague-Dawley , Transcrição Genética
16.
Stem Cell Res Ther ; 11(1): 361, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: covidwho-719615

RESUMO

BACKGROUND: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. OBJECTIVES: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. METHODS: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. MEASUREMENTS AND MAIN RESULTS: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. CONCLUSIONS: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Cordão Umbilical/citologia , Adulto , Idoso , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Proteína C-Reativa/metabolismo , China , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Humanos , Interleucina-6/metabolismo , Contagem de Linfócitos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Taxa de Sobrevida , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Transplante Homólogo , Resultado do Tratamento
17.
Cell Transplant ; 29: 963689720952089, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-729480

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, originating from Wuhan, China, is known to cause severe acute respiratory symptoms. The occurrence of a cytokine storm in the lungs is a critical step in the disease pathogenesis, as it causes pathological lesions, pulmonary edema, and acute respiratory distress syndrome, potentially resulting in death. Currently, there is no effective treatment that targets the cytokine storm and helps regenerate the damaged tissue. Mesenchymal stem cells (MSCs) are known to act as anti-inflammatory/immunomodulatory candidates and activate endogenous regeneration. As a result, MSC therapy is a potential treatment approach for COVID-19. Intravenous injection of clinical-grade MSCs into COVID-19 patients can induce an immunomodulatory response along with improved lung function. Dental pulp stem cells (DPSCs) are considered a potential source of MSCs for immunomodulation, tissue regeneration, and clinical application. Although some current clinical trials have treated COVID-19 patients with DPSCs, this therapy has not been approved. Here, we review the potential use of DPSCs and their significance in the development of a therapy for COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Polpa Dentária/citologia , Imunomodulação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Pneumonia Viral/terapia , Betacoronavirus/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Polpa Dentária/imunologia , Humanos , Imunoterapia/métodos , Inflamação/imunologia , Inflamação/terapia , Pulmão/imunologia , Pulmão/fisiologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/terapia , Células-Tronco Mesenquimais/citologia , Pandemias , Pneumonia Viral/imunologia , Regeneração
18.
Stem Cell Res Ther ; 11(1): 356, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: covidwho-712864

RESUMO

BACKGROUND: The outbreak of a new virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become the main health concern all over the world. Since effective antiviral treatments have not been developed until now, SARS-CoV-2 is severely affecting countries and territories around the world. METHODS: At the present review, articles in PubMed were searched with the following terms: mesenchymal stem cells, exosomes, coronavirus, and SARS-CoV-2, either alone or in a combination form. The most relevant selected functions were mesenchymal stem cell-derived exosomes and SARS-CoV-2 virus infection. RESULTS: SARS-CoV-2 could damage pulmonary cells and induce secretion of different types of inflammatory cytokines. In the following, these cytokines trigger inflammation that damages the lungs and results in lethal acute respiratory distress syndrome (ARDS). The main characteristic of ARDS is the onset of inflammation in pulmonary, hyaline formation, pulmonary fibrosis, and edema. Mesenchymal stem cell-derived exosomes (MSC-Exo) are believed to have anti-inflammatory effects and immune-modulating capacity as well as the ability to induce tissue regeneration, suggesting a significant therapeutic opportunity that could be used to SARS-CoV-2 pneumonia treatment. Besides, exosomes may serve as a biomarker, drug delivery system, and vaccine for the management of the patient with SARS-CoV-2. CONCLUSION: MSC-Exo may serve as a promising tool in the treatment of SARS-CoV-2 pneumonia. However, further work needs to be carried out to confirm the efficacy of exosomes in the treatment of SARS-CoV-2 pneumonia.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/terapia , Exossomos/transplante , Pneumonia Viral/terapia , Betacoronavirus/isolamento & purificação , Biomarcadores/metabolismo , Coronavirus/isolamento & purificação , Coronavirus/patogenicidade , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pandemias , Pneumonia Viral/virologia
19.
Stem Cell Res Ther ; 11(1): 356, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795359

RESUMO

BACKGROUND: The outbreak of a new virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become the main health concern all over the world. Since effective antiviral treatments have not been developed until now, SARS-CoV-2 is severely affecting countries and territories around the world. METHODS: At the present review, articles in PubMed were searched with the following terms: mesenchymal stem cells, exosomes, coronavirus, and SARS-CoV-2, either alone or in a combination form. The most relevant selected functions were mesenchymal stem cell-derived exosomes and SARS-CoV-2 virus infection. RESULTS: SARS-CoV-2 could damage pulmonary cells and induce secretion of different types of inflammatory cytokines. In the following, these cytokines trigger inflammation that damages the lungs and results in lethal acute respiratory distress syndrome (ARDS). The main characteristic of ARDS is the onset of inflammation in pulmonary, hyaline formation, pulmonary fibrosis, and edema. Mesenchymal stem cell-derived exosomes (MSC-Exo) are believed to have anti-inflammatory effects and immune-modulating capacity as well as the ability to induce tissue regeneration, suggesting a significant therapeutic opportunity that could be used to SARS-CoV-2 pneumonia treatment. Besides, exosomes may serve as a biomarker, drug delivery system, and vaccine for the management of the patient with SARS-CoV-2. CONCLUSION: MSC-Exo may serve as a promising tool in the treatment of SARS-CoV-2 pneumonia. However, further work needs to be carried out to confirm the efficacy of exosomes in the treatment of SARS-CoV-2 pneumonia.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/terapia , Exossomos/transplante , Pneumonia Viral/terapia , Betacoronavirus/isolamento & purificação , Biomarcadores/metabolismo , Coronavirus/isolamento & purificação , Coronavirus/patogenicidade , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pandemias , Pneumonia Viral/virologia
20.
Stem Cell Res Ther ; 11(1): 361, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811531

RESUMO

BACKGROUND: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. OBJECTIVES: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. METHODS: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. MEASUREMENTS AND MAIN RESULTS: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. CONCLUSIONS: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Cordão Umbilical/citologia , Adulto , Idoso , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Proteína C-Reativa/metabolismo , China , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Humanos , Interleucina-6/metabolismo , Contagem de Linfócitos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Taxa de Sobrevida , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Transplante Homólogo , Resultado do Tratamento
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