Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.690
Filtrar
1.
J Transl Med ; 18(1): 359, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958009

RESUMO

More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Animais , Ensaios Clínicos como Assunto , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Pesquisa Médica Translacional
2.
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
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.
Rinsho Ketsueki ; 61(8): 953-958, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908060

RESUMO

Expanded human bone marrow-derived mesenchymal stromal/stem cells (MSC) have been used in the treatment of acute graft-versus-host disease (GVHD). It is currently accepted that the use of allogeneic off-the-shelf MSC has therapeutic efficacy with no apparent serious early-onset adverse effects; however, further development would be needed to overcome the current situation of MSC therapy for intractable GVHD. In the emerging recognition of the importance of extracellular vesicles (EV) as modulators of cell-cell communication physiologically and pathologically, we recently revealed that human bone marrow MSC-derived EV ameliorate GVHD clinically and pathologically through the preservation of peripheral naïve T-cell populations in a murine model. In this article, we summarize future perspectives on MSC-based therapy for GVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Humanos , Camundongos , Linfócitos T
5.
Int J Mol Sci ; 21(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899381

RESUMO

Respiratory and pulmonary diseases are among the leading causes of death globally. Despite tremendous advancements, there are no effective pharmacological therapies capable of curing diseases such as COPD (chronic obstructive pulmonary disease), ARDS (acute respiratory distress syndrome), and COVID-19. Novel and innovative therapies such as advanced therapy medicinal products (ATMPs) are still in early development. However, they have exhibited significant potential preclinically and clinically. There are several longitudinal studies published, primarily focusing on the use of cell therapies for respiratory diseases due to their anti-inflammatory and reparative properties, thereby hinting that they have the capability of reducing mortality and improving the quality of life for patients. The primary objective of this paper is to set out a state of the art review on the use of aerosolized MSCs and their potential to treat these incurable diseases. This review will examine selected respiratory and pulmonary diseases, present an overview of the therapeutic potential of cell therapy and finally provide insight into potential routes of administration, with a focus on aerosol-mediated ATMP delivery.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Doença Pulmonar Obstrutiva Crônica/terapia , Síndrome do Desconforto Respiratório do Adulto/terapia , Animais , Humanos , Transplante de Células-Tronco Mesenquimais/instrumentação , Nebulizadores e Vaporizadores , Pandemias
6.
Pain Physician ; 23(4S): S391-S420, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32942796

RESUMO

BACKGROUND: Although only a small percentage of patients with COVID-19 deteriorate to a critical condition, because of the associated high mortality rate and the sheer number of cases, it imposes a tremendous burden on the society and unprecedented strains the health care resources. Albeit lung is the primary organ involved resulting in acute respiratory distress syndrome (ARDS), many patients additionally present with secondary multiorgan failure. Unfortunately, there is no definitive or curative treatment for this condition, and the management has been predominantly confined to supportive care, which necessitates an urgent need for novel therapies. Mesenchymal stem cell (MSC) therapy has a vast array of preclinical data and early, preliminary clinical data that suggests its potential to regenerate and restore the function of damaged tissues and organs. To date, there has been no review of all the clinical trials that have assessed the safety and efficacy of MSC therapy in organ failure commonly seen in seriously complicated COVID-19 patients. OBJECTIVES: To evaluate the effectiveness of MSC therapy in managing multiorgan failure, utilizing currently available literature. STUDY DESIGN: A review of human randomized controlled trials (RCTs) and observational studies assessing the role of MSC therapy in managing multiorgan failure. METHODS: PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1990 through May 2020. Studies that included embryonic stem cells, induced pluripotent stem cells, differentiated MSCs into specific lineage cells, and hematopoietic stem cells were excluded. Trials with intraorgan infiltration of MSC were also excluded. OUTCOME MEASURES: The primary outcome evaluated the improvement in clinical assessment scores and indices of organ function. The secondary outcome assessed the safety of MSC therapy in the clinical trials. RESULTS: Based on search criteria, 12 studies were found for lung, 52 for heart, 23 for liver, 16 for stroke, and 9 for kidney. Among the 6 studies that specifically assessed the effectiveness of MSC therapy in ARDS, 4 showed positive outcomes. Forty-one of the 52 trials that examined ischemic and nonischemic heart failure reported beneficial effects. Twenty of 23 trials for liver failure from different etiologies revealed favorable outcomes. Nine out of the 15 studies evaluating stroke had satisfactory effects. However, only 3 out of the 9 studies for kidney failure showed positive results. Nonexpanded bone marrow mononuclear cells were used in most of the negative studies. The incidence of disease worsening or major complications was extremely rare from MSC therapy. LIMITATIONS: Among the studies evaluated, although there were many RCTs, there were also numerous case series. Additionally, most recruited a small number of patients. CONCLUSIONS: MSC therapy seems to be promising to treat multiorgan failure from COVID-19. More studies are urgently needed to assess both safety and efficacy.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Insuficiência de Múltiplos Órgãos/terapia , Insuficiência de Múltiplos Órgãos/virologia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Betacoronavirus , Humanos , Estudos Observacionais como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
7.
Pain Physician ; 23(4S): S421-S432, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32942797

RESUMO

OBJECTIVE: There are as yet no effective strategies to treat the novel COVID-19 and to stem its symptoms, including ARDS. This review examines recent research studies in humans to determine whether mesenchymal stem cells (MSCs) may be used effectively and safely to target potentially deadly lung damage that may follow infection. METHODS: A literature search was conducted to find published manuscripts on the treatment of ARDS and COVID-19 symptoms, disease presentation, and available treatment regimens. Electronic data bases of scientific articles and records of printed documents of JAMA journals were searched to find research publications on MSC treatment of ARDS and COVID-19. Outcome variables included mortality over varying time periods, hospital days, days on ventilator, and biological factors. RESULTS: Two randomized double-blind clinical trials, 2 pilot studies, and 2 case reports described MSC use to treat ARDS with specific focus on COVID-19 and lung symptoms of cytokine storm. The MSCs were well-tolerated across studies. No significant differences in treatment outcome were found in randomized double-blind trials; however, results of 1 pilot study and 1 case report showed that MSCs led to lung symptom resolution and survival in severely ill treatment patients. CONCLUSIONS: There is little published research on disease and survival outcomes among patients suffering severe lung disease associated with ARDS and COVID-19, and studies available are limited by lack of consistency in design and numerous flaws and limitations. Comparisons across studies are difficult. Nevertheless, it is documented that 8 ARDS patients with COVID-19 experienced symptom recovery and survival subsequent to MSC administration. MSCs are potentially life-saving treatment approaches for some patients who exhibit severe lung distress and have not responded to standard treatments. This is an obviously exciting research and treatment option for COVID-19 and other life-threatening diseases.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/terapia , Síndrome do Desconforto Respiratório do Adulto/virologia , Betacoronavirus , Feminino , Humanos , Pandemias , Resultado do Tratamento
8.
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
9.
Medicine (Baltimore) ; 99(31): e21429, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756149

RESUMO

RATIONALE: The COVID-19 cases increased very fast in January and February 2020. The mortality among critically ill patients, especially the elder ones, is relatively high. Considering many patients died of severe inflammation response, it is urgent to develop effective therapeutic strategies for these patients. The human umbilical cord mesenchymal stem cells (hUCMSCs) have shown good capabilities to modulate the immune response and repair the injured tissue. Therefore, investigating the potential of hUCMSCs to the treatment of COVID-19 critically ill patients is necessary. PATIENT CONCERNS: A 65-year-old woman felt fatigued and had a fever with body temperature of 38.2C, coughed up white foaming sputum. After 1 day, she had chest tightness with SPO2 of 81%, and blood pressure of 160/91 mm Hg. DIAGNOSE: According to the guideline for the diagnosis and treatment of 2019 novel coronavirus infected pneumonia (Trial 4th Edition), COVID-19 was diagnosed, based on the real-time RT-PCR test of SARS-CoV-2. INTERVENTIONS: After regular treatment for 12 days, the inflammation symptom of the patient was still very severe and the potential side effects of corticosteroid were observed. Then, allogenic hUCMSCs were given 3 times (5 × 10 cells each time) with a 3-day interval, together with thymosin α1 and antibiotics daily injection. OUTCOMES: After these treatments, most of the laboratory indexes and CT images showed remission of the inflammation symptom. The patient was subsequently transferred out of ICU, and the throat swabs test reported negative 4 days later. LESSONS: These results indicated the clinical outcome and good tolerance of allogenic hUCMSCs transfer.


Assuntos
Betacoronavirus , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Idoso , Antibacterianos/uso terapêutico , Terapia Combinada , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Feminino , Humanos , Pandemias , Pneumonia Viral/virologia , Timalfasina/uso terapêutico , Resultado do Tratamento
10.
Medicine (Baltimore) ; 99(34): e21646, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846775

RESUMO

INTRODUCTION: People with multiple sclerosis (PwMS) experience a wide range of disabilities which negatively impact their quality of life (QOL). Several interventions have been used in PwMS such as medication, physical therapy exercises and stem cell therapy to improve their QOL. However, there is a limited evidence on the benefits of combining interventions. The purpose of this study is to explore the effect of combining physical therapy exercises (PTE) and Wharton Jelly mesenchymal stem cell (WJ-MSCs) injections on motor and non-motor symptoms versus each intervention alone in PwMS. METHODS: Sixty PwMS will be allocated to either PTE, WJ-MSCs, or a combined group, followed up for 12 months and examined using a comprehensive battery of measures. Participants in the PTE group will receive 2 sessions per week of a supervised exercise program for 6 months followed by a home exercise program for another 6 months. The WJ-MSCs group will receive 3 WJ-MSCs injections in the first 6 months then they will be encouraged to follow an active life style. The third group will receive both interventions. DISCUSSION: This study will aid in a better understanding of the combined effect of physical therapy and mesenchymal stem cell therapy. The results from this proposed study may reduce disability, improve QOL in PwMS, and consequently, reduce the cost associated with the life-time care of these individuals worldwide. TRIAL REGISTRATION NUMBER: NCT03326505.


Assuntos
Terapia por Exercício , Transplante de Células-Tronco Mesenquimais , Esclerose Múltipla/terapia , Terapia Combinada , Humanos , Injeções , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego
11.
Sci Adv ; 6(30): eaba6884, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32832666

RESUMO

More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies. However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Pneumonia Viral/terapia , Técnicas de Cultura Celular por Lotes/métodos , Reatores Biológicos , Infecções por Coronavirus/virologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Engenharia Metabólica/métodos , Pandemias , Pneumonia Viral/virologia , Transplantados
12.
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
13.
Medicine (Baltimore) ; 99(34): e21846, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846833

RESUMO

INTRODUCTION: Stroke often causes residual hemiparesis, and upper extremity motor impairment is usually more disabling than lower extremity in those who are suffering from post-stroke hemiparesis. Cell therapy is one of the promising therapies to reduce post-stroke disability. PATIENT CONCERNS: Three male participants were included in the study to investigate the feasibility and tolerability of autologous adipose tissue derived stromal vascular fraction. DIAGNOSIS: All participants had hemiparesis after 1st-ever stroke longer than 6 months previously. INTERVENTIONS: Under general anesthesia, liposuction of abdominal subcutaneous fat was performed. Stromal vascular fraction freshly isolated from the adipose tissue extract was injected into the muscles of paretic upper extremity. All participants received inpatient stroke rehabilitation consisted of physical and occupational therapy more than 3 hours a day for 2 months or more. OUTCOMES: The whole procedure did not produce any significant adverse event in all participants. Adipose tissue extracts yielded sufficient stromal cells. One participant showed clinically important change in upper extremity Fugl-Meyer assessment after the injection and it lasted up to 6 months. Functional magnetic resonance imaging showed concomitant increase in ipsilesional cortical activity. The other 2 participants did not show remarkable changes. LESSONS: Intramuscular injection of autologous adipose tissue derived stromal vascular fraction seems to be a safe and tolerable procedure in subjects with chronic stroke, and its utility in rehabilitation needs further investigation.


Assuntos
Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/transplante , Transplante de Células-Tronco Mesenquimais/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Células Estromais/transplante , Tecido Adiposo/citologia , Adulto , Hemorragia Cerebral/complicações , Humanos , Injeções Intramusculares , Lipectomia/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Células-Tronco Mesenquimais , Terapia Ocupacional/métodos , Paresia/fisiopatologia , Paresia/reabilitação , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Células Estromais/citologia , Extremidade Superior/fisiopatologia
14.
Cell Transplant ; 29: 963689720940719, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841042

RESUMO

Coronavirus disease 2019 or COVID-19 is highly infectious, which can lead to acute and chronic debilitating symptoms, as well as mortality. The advent of safe and effective vaccines or antiviral drugs remains distant in the future. Practical public health measures, such as social distancing, hand washing, and wearing a face mask, are the current recommended guidelines by the Centers for Disease Control and Prevention for limiting the spread of the virus. Weakened immune system and aberrant inflammation represent a major pathological symptom of COVID-19 patients. Based on the unique immunomodulatory properties of both convalescent plasma and stem cells, we discuss here their potential use for treating COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Anticorpos Neutralizantes/uso terapêutico , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Humanos , Imunização Passiva/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Prática de Saúde Pública , Carga Viral
15.
Cell Biol Int ; 44(11): 2182-2191, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32767687

RESUMO

Since its eruption in China, novel coronavirus disease (COVID-19) has been reported in most of the countries and territories (>200) of the world with ∼18 million confirmed cases (as of August 3, 2020). In most of the countries, COVID-19 upsurge is uncontrolled with a significant mortality rate. Currently, no treatment effective for COVID-19 is available in the form of vaccines or antiviral drugs and patients are currently treated symptomatically. Although the majority of the patients develop mild symptoms and recover without mechanical ventilation for respiratory management, severe respiratory illness develops in a significant portion of affected patients and may result in death. While the scientific community is working to develop vaccines and drugs against the COVID-19 pandemic, novel alternative therapies may reduce the mortality rate. Recent use of stem cells for critically ill COVID-19 patients in a small group of patients in China and subsequent Emergency Use Authorization of stem cells by Food and Drug Administration to Global Institute of Stem Cell Therapy and Research and Athersys has created excitement among the medical community. As a result, several clinical trials have been registered using stem cells for COVID-19 treatment that aim to use different cell sources, dosage, and importantly diverse targeted patient groups. In this brief review, the possibilities of stem cell use in COVID-19 patients and relevant challenges in their use have been discussed.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Transplante de Células-Tronco/métodos , Animais , Betacoronavirus/isolamento & purificação , Ensaios Clínicos como Assunto , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Pandemias
16.
Hum Cell ; 33(4): 907-918, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32780299

RESUMO

Acute respiratory distress syndrome (ARDS) is the main cause for the COVID-19 infection-related morbidity and mortality. Recent clinical evidences suggest increased level of cytokines and chemokines targeting lung tissue as a prominent etiological factor. The immunomodulatory effect of mesenchymal stem cells (MSCs) as the alternative therapy for the treatment of inflammatory and autoimmune diseases is well known. Several studies have also revealed that similar therapeutic impacts of parent MSCs are also exhibited by MSCs-derived extracellular vesicles (EVs) including exosomes. In this review, we explored the therapeutic potential of both MSCs and exosomes in mitigating the COVID-19 induced cytokine storm as well as promoting the regeneration of alveolar tissue, attributed to the intrinsic cytokines and growth factor present in the secretome. The preliminary studies have demonstrated the safety and efficacy of MSCs and exosomes in mitigating symptoms associated with COVID-19. Thus, they can be used on compassionate basis, owing to their ability to endogenously repair and decrease the inflammatory reactions involved in the morbidity and mortality of COVID-19. However, more preclinical and clinical studies are warranted to understand their mechanism of action and further establish their safety and efficacy.


Assuntos
Infecções por Coronavirus/terapia , Exossomos , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Células-Tronco Mesenquimais/imunologia , Pandemias , Pneumonia Viral/etiologia , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Síndrome do Desconforto Respiratório do Adulto/terapia
17.
Signal Transduct Target Ther ; 5(1): 172, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855385

RESUMO

No effective drug treatments are available for coronavirus disease 2019 (COVID-19). Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage, death, or long-term functional disability in survivors require clinical evaluation. We performed a parallel assigned controlled, non-randomized, phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease. The study enrolled 18 hospitalized patients with COVID-19 (n = 9 for each group). The treatment group received three cycles of intravenous infusion of UC-MSCs (3 × 107 cells per infusion) on days 0, 3, and 6. Both groups received standard COVID-treatment regimens. Adverse events, duration of clinical symptoms, laboratory parameters, length of hospitalization, serial chest computed tomography (CT) images, the PaO2/FiO2 ratio, dynamics of cytokines, and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed. No serious UC-MSCs infusion-associated adverse events were observed. Two patients receiving UC-MSCs developed transient facial flushing and fever, and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion. Mechanical ventilation was required in one patient in the treatment group compared with four in the control group. All patients recovered and were discharged. Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated. Phase 2/3 randomized, controlled, double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Infecções por Coronavirus/terapia , Células-Tronco Hematopoéticas/virologia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Adulto , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Combinação de Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lopinavir , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Respiração Artificial , Ritonavir , Índice de Gravidade de Doença , Resultado do Tratamento
18.
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
19.
Life Sci ; 258: 118185, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32750438

RESUMO

AIMS: The immune response is essential for the control and resolution of viral infections. Following the outbreak of novel coronavirus disease (COVID-19), several immunotherapies were applied to modulate the immune responses of the affected patients. In this review, we aimed to describe the role of the immune system in response to COVID-19. We also provide a systematic review to collate and describe all published reports of the using immunotherapies, including convalescent plasma therapy, monoclonal antibodies, cytokine therapy, mesenchymal stem cell therapy, and intravenous immunoglobulin and their important outcomes in COVID-19 patients. MATERIAL AND METHODS: A thorough search strategy was applied to identify published research trials in PubMed, Scopus, Medline, and EMBASE from Dec 1, 2019, to May 4, 2020, for studies reporting clinical outcomes of COVID-19 patients treated with immunotherapies along with other standard cares. KEY FINDINGS: From an initial screen of 80 identified studies, 24 studies provided clinical outcome data on the use of immunotherapies for the treatment of COVID-19 patients, including convalescent plasma therapy (33 patients), monoclonal antibodies (55 patients), interferon (31 patients), mesenchymal stem cell therapy (8 patient), and immunoglobulin (63 patients). Except for nine severe patients who died after treatment, most patients were recovered from COVID-19 with improved clinical symptoms and laboratory assessment. SIGNIFICANCE: Based on the available evidence, it seems that treatment with immunotherapy along with other standard cares could be an effective and safe approach to modulate the immune system and improvement of clinical outcomes.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/terapia , Imunoterapia/métodos , Pneumonia Viral/terapia , Anticorpos Monoclonais/uso terapêutico , Infecções por Coronavirus/imunologia , Humanos , Imunização Passiva/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Interferons/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Pandemias , Pneumonia Viral/imunologia , Resultado do Tratamento
20.
Sheng Li Xue Bao ; 72(4): 426-432, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32820304

RESUMO

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 ß-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.


Assuntos
Apoptose , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Proteínas de Ciclo Celular , Sobrevivência Celular , Senescência Celular , Fatores de Transcrição Forkhead , Humanos , Fatores de Transcrição , Cordão Umbilical
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA