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2.
Anticancer Res ; 40(10): 5687-5700, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988894

RESUMO

BACKGROUND: We previously developed a novel technique for expanding highly activated and purified natural killer (NK) cells able to maximize the theoretical activation potential of NK cells; thus, we named this cell population zenithal-NK (ZNK). AIM: To evaluate the safety, feasibility, and preliminary efficacy of autologous ZNK cells in patients with different types of advanced cancer with measurable solid lesions. PATIENTS AND METHODS: In this phase I/IIb first-in-human, open-label, dose-escalation study (trial registration ID: UMIN-000011555), eligible patients received ZNK cells intravenously starting from 106 to 108 cells/patient/dose at 2-week dosing intervals. A maximum of six cycles were allowed. Safety and survival analyses were also carried out for cases that were excluded and never administered ZNK cells. RESULTS: As of April 20, 2017, a total of nine patients were enrolled in this study, with one recruited twice. Overall, neither grade 2 or higher toxicities (Common Terminology Criteria for Adverse Events v5.0) caused by cell administration, nor adverse events causing discontinuation of protocol treatment were found. In four cases, the number of administered ZNK cells was increased to 108 cells/body/dose without any serious dose-limiting toxicity; the maximally tolerated dose was therefore considered to be at least 108 cells. The overall response rate was 40.0% in 10 net cases, one of partial response and three of stable disease, and the patient with partial response is still alive after 4 year's observation. CONCLUSION: These results demonstrate that autologous ZNK cells are safe and well-tolerated in patients with different types of advanced solid tumors. Clinical studies using similarly active ZNK cells from human leukocyte antigen/killer cell immunoglobulin-like receptor-mismatched healthy donors under Good Manufacturing Practice-compliant manufacturing, and with modified treatment regimen, i.e. doses and frequencies, are warranted for further investigation to show the potential of ZNK cells in such patients.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Células Matadoras Naturais/transplante , Neoplasias/terapia , Transplante Autólogo/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/genética , Relação Dose-Resposta Imunológica , Feminino , Humanos , Células Matadoras Naturais/imunologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia
3.
J Endod ; 46(9S): S175-S188, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950189

RESUMO

INTRODUCTION: Regenerative medicine offers innovative approaches to restore damaged tissues on the basis of tissue engineering (TE). Although research on advanced therapy medicinal products (ATMPs) has been very active in recent years, the number of licensed products remains surprisingly low and restricted to the treatment of severe, incurable diseases. METHODS: This paper provides a critical review of current literature on the regulatory, clinical, and commercial status of ATMP-based therapies in the EU and worldwide and the hurdles to overcome for their broader application in Regenerative Dentistry. RESULTS: Competent authorities have focused on developing regulatory pathways to address unmet patient needs. Oncology represents the dominating field, followed by cardiovascular, musculoskeletal, neurodegenerative, immunologic, and inherited diseases. Yet, the status remains in early development, and scientific, regulatory, and cost-effectiveness issues impose considerable hurdles toward marketing authorization, technology adoption, and patient accessibility. In this context, although regenerative dentistry has achieved breakthrough innovations in TE of several dental/oral tissues in preclinical models, it has hardly harnessed research progress to integrate innovative regenerative treatments into clinical practice. CONCLUSION: Global demographic changes, which demonstrate a steady increase of the aging population, highlight the societal need for the application of ATMP-based therapies in the treatment of noncommunicable diseases (NCDs). Although oral diseases, as an integral part of NCDs, are not life-threatening and largely preventable, they sustain high prevalence, with severe burden on economy and quality of life. In this perspective, the urgent request to ultimately translate draining research in dental TE conducted during the last decades into innovative treatments brought safely and cost-effectively into society at large still holds the stage. This review provides an overview of the regulatory, clinical, and commercial status of ATMP-based therapies in the European Union and worldwide and the hurdles to overcome for their broader application in regenerative dentistry.


Assuntos
Qualidade de Vida , Medicina Regenerativa , Idoso , Terapia Baseada em Transplante de Células e Tecidos , Odontologia , Humanos , Engenharia Tecidual
4.
PLoS Negl Trop Dis ; 14(8): e0008635, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32853206

RESUMO

BACKGROUND: In view of the potential immunosuppressive and regenerative properties of mesenchymal stem cells (MSC), we investigated whether transplantation of adipose tissue-derived stem cells (ASC) could be used to control the granulomatous reaction in the liver of mice infected with Schistosoma mansoni after Praziquantel (PZQ) treatment. METHODOLOGY/PRINICPAL FINDINGS: C57BL/6 mice infected with S. mansoni were treated with PZQ and transplanted intravenously with ASC from uninfected mice. Liver morpho-physiological and immunological analyses were performed. The combined PZQ/ASC therapy significantly reduced the volume of hepatic granulomas, as well as liver damage as measured by ALT levels. We also observed that ASC accelerated the progression of the granulomatous inflammation to the advanced/curative phase. The faster healing interfered with the expression of CD28 and CTLA-4 molecules in CD4+ T lymphocytes, and the levels of IL-10 and IL-17 cytokines, mainly in the livers of PZQ/ASC-treated mice. CONCLUSIONS: Our results show that ASC therapy after PZQ treatment results in smaller granulomas with little tissue damage, suggesting the potential of ASC for the development of novel therapeutic approaches to minimize hepatic lesions as well as a granulomatous reaction following S. mansoni infection. Further studies using the chronic model of schistosomiasis are required to corroborate the therapeutic use of ASC for schistosomiasis.


Assuntos
Tecido Adiposo/fisiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Hepatopatias/terapia , Fígado/parasitologia , Praziquantel/uso terapêutico , Esquistossomose/tratamento farmacológico , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Granuloma , Fígado/metabolismo , Fígado/patologia , Hepatopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Schistosoma mansoni , Esquistossomose/patologia , Esquistossomose mansoni
5.
PLoS One ; 15(8): e0236600, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756610

RESUMO

Cell therapy is a promising treatment. One of the key aspects of cell processing products is ensuring sterility of cell-processing facilities (CPFs). The objective of this study was to assess the environmental risk factors inside and outside CPFs. We monitored the temperature, humidity, particle number, colony number of microorganisms, bacteria, fungi, and harmful insects in and around our CPF monthly over one year. The temperature in the CPF was constant but the humidity fluctuated depending on the humidity outside. The particle number correlated with the number of entries to the room. Except for winter, colonies of microorganisms and harmful insects were detected depending on the cleanliness of the room. Seven bacterial and two fungal species were identified by PCR analyses. Psocoptera and Acari each accounted for 41% of the total trapped insects. These results provide useful data for taking the appropriate steps to keep entire CPFs clean.


Assuntos
Centros Médicos Acadêmicos/normas , Poluição do Ar em Ambientes Fechados/efeitos adversos , Terapia Baseada em Transplante de Células e Tecidos/normas , Monitoramento Ambiental , Microbiologia do Ar/normas , Bactérias/patogenicidade , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Humanos , Japão/epidemiologia , Exposição Ocupacional/efeitos adversos , Medição de Risco
6.
Life Sci ; 258: 118181, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32763291

RESUMO

About 17% of couples suffer from infertility conditions, worldwide. The most common reasons for female infertility are ovulation disorders, fallopian-related disorders, RM, RIF, endometriosis, and unexplained infertility. Despite advances in Assisted Reproductive Technologies, infertility has remained a serious problem. In recent years, a considerable progress in cell therapy as an emerging approach for the treatment infertility has been made. Cell therapy involves utilizing lymphocytes, platelet -rich plasma, PBMCs and different types of stem cells as therapeutic agents. Stem cells are usually multipotent cells existed in embryos, fetuses, and adults that proliferate and differentiate into different cell types under certain circumstances. The main types of stem cells are embryonic stem cells, decidual stromal cells, MSCs, human amniotic epithelial cells, and induced pluripotent-stem cells each functioning in a different way. The advantages of using stem cells as therapeutic agents are convenient sampling, abundant sources, and avoidable ethical issues. Lymphocyte immunotherapy, a simple and cost effective method, can be safe and useful approach if performed with proper dose of fresh lymphocytes intradermally before and during pregnancy. Overall, cell therapy mechanism of actions are inducing the production of cytokines, blocking antibodies and growth factors, proliferation of B10 cells, reducing the activity of NK cells, increasingTh2 and Treg cells and decreasing Th1 and Th17 cells. Cell therapy can be an effective strategy as it provides an interactive, dynamic, specific and individualized treatment. Although cell therapy is a promising approach, it still needs more investigation in order to improve and make it safer.


Assuntos
Aborto Habitual/terapia , Terapia Baseada em Transplante de Células e Tecidos , Implantação do Embrião , Infertilidade Feminina/terapia , Feminino , Humanos , Reprodução
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1189-1196, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798397

RESUMO

OBJECTIVE: To investigate the prognosis prediction value of PET/CT in DLBCL patients treated with CAR-T therapy. METHODS: The effects of PET/CT were retrospectively explored on 13 R/R DLBCL patients who were treated with CAR-T therapy. Parameters reflecting tumor metabolic burden, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured before and after CAR-T treatment. RESULTS: Patients with larger baseline MTV or longer sum of longest diameters showed shorter overall survival (OS) time than those with low tumor burden. Patients achieved complete remission (CR), partial remission (PR) and minor remission (MR) determined by response evaluation criteria in lymphoma (RECIL) in 12 weeks showed progression-free survival and OS time superior to those of patients with no remission. In addition, it was found that 2 patients with residual masses classified as PR by contrast-enhanced CT of patients were evaluated as complete metabolic response by PET/CT imaging. CONCLUSION: PET/CT shows a great value in the evaluation of prognosis and response in CAR-T-treated R/R DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Terapia Baseada em Transplante de Células e Tecidos , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons , Prognóstico , Receptores de Antígenos Quiméricos , Estudos Retrospectivos
9.
Lancet Haematol ; 7(9): e690-e696, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32791043

RESUMO

People living with HIV are a global population with increased cancer risk but their access to modern immunotherapies for cancer treatment has been limited by socioeconomic factors and inadequate research to support safety and efficacy in this population. These immunotherapies include immune checkpoint inhibitors and advances in cellular immunotherapy, particularly chimeric antigen receptor (CAR) T-cell therapy. Despite the field of cancer immunotherapy rapidly expanding with ongoing clinical trials, people with HIV are often excluded from such trials. In 2019, post-approval evaluation of anti-CD19 CAR T-cell therapy in people with HIV and aggressive B-cell lymphoma showed the feasibility of CAR T-cell therapy for cancer in this excluded group. Along with expanded treatment options for people with HIV is the ability to assess the effects of immunotherapy on the latent HIV reservoir, with certain immunotherapies showing the ability to alleviate this burden. This Series paper addresses the increased cancer burden in people with HIV, the increasing evidence for the safety and efficacy of immunotherapies in the context of HIV and cancer, and opportunities for novel applications of CAR-T therapy for the treatment of both haematological malignancies and HIV.


Assuntos
Infecções por HIV/patologia , Neoplasias Hematológicas/terapia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/transplante , Antígenos CD19/imunologia , Terapia Baseada em Transplante de Células e Tecidos , Infecções por HIV/complicações , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Humanos , Imunoterapia Adotiva , Taxa de Sobrevida , Linfócitos T/citologia , Linfócitos T/metabolismo
12.
Brasília; s.n; 3 jul. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117627

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 10 artigos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Vacina BCG/uso terapêutico , Cloroquina/uso terapêutico , Estudos Transversais , Estudos de Coortes , Azitromicina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos , Hidroxicloroquina/uso terapêutico
13.
Stem Cell Res Ther ; 11(1): 305, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698898

RESUMO

Acute respiratory distress syndrome (ARDS) develops rapidly and has a high mortality rate. Survivors usually have low quality of life. Current clinical management strategies are respiratory support and restricted fluid input, and there is no suggested pharmacological treatment. Mesenchymal stromal cells (MSCs) have been reported to be promising treatments for lung diseases. MSCs have been shown to have a number of protective effects in some animal models of ARDS by releasing soluble, biologically active factors. In this review, we will focus on clinical progress in the use of MSCs as a cell therapy for ARDS, which may have clinical implications during the coronavirus disease 2019 (COVID-19) pandemic.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/terapia , Betacoronavirus , Síndrome da Liberação de Citocina/terapia , Humanos , Células-Tronco Mesenquimais , Pandemias
14.
Anticancer Res ; 40(8): 4729-4740, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727799

RESUMO

BACKGROUND/AIM: In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy using T lymphocytes activated in vitro with or without dendritic cell vaccination in combination with standard therapies in terms of the survival of patients with advanced or recurrent endometrial and cervical cancers of the uterus. PATIENTS AND METHODS: A total of 187 patients with advanced or recurrent uterine cancer were enrolled in this study. The correlation between overall survival and various clinical factors was examined by univariate and multivariate analyses. RESULTS: Univariate analysis revealed that the prognosis was improved in uterine cancer patients who received immune-cell therapy without prior chemotherapy or without distant metastasis. Multivariate analysis demonstrated that the absence of prior chemotherapy for endometrial cancer and liver/lung metastasis of cervical cancer are indications for immune-cell therapy. CONCLUSION: Survival benefit in uterine cancer patients could be potentially obtained by a combination of immune-cell therapy with other therapies.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias Uterinas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Baseada em Transplante de Células e Tecidos/métodos , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Linfócitos T/patologia , Resultado do Tratamento , Útero/patologia
15.
Anticancer Res ; 40(8): 4741-4748, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727800

RESUMO

BACKGROUND/AIM: We aimed to investigate the efficacy of immune-cell therapy in terms of the survival of patients with neuroendocrine carcinoma of the uterine cervix (NECC), which lacks standardized therapeutic approaches. PATIENTS AND METHODS: We identified 17 patients who were diagnosed as having NECC and treated with immune-cell therapy. The clinical characteristics of these patients were extracted from their records and their overall survival was measured. RESULTS: Of the 17 patients, two patients with early-stage NECC without recurrence and three patients with less than four treatments were excluded. The median survival times from the time of diagnosis and from the initial administration of immune-cell therapy were 49.7 and 24.4 months, respectively. The overall survival rates at 1, 2, and 5 years were 63.6%, 38.2%, and 25.5%, respectively. Long-term survival was observed in the patients with distant metastases. CONCLUSION: The preliminary results of this retrospective study suggested the potential efficacy of immune-cell therapy for NECC.


Assuntos
Carcinoma Neuroendócrino/imunologia , Carcinoma Neuroendócrino/terapia , Colo do Útero/patologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/terapia , Adulto , Carcinoma Neuroendócrino/patologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Feminino , Humanos , Imunoterapia Adotiva/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias/métodos , Prognóstico , Neoplasias do Colo do Útero/patologia
16.
PLoS One ; 15(7): e0236038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658933

RESUMO

The attenuation of hyper-inflammation in sepsis with the administration of anti-inflammatory macrophages is an interesting adjuvant therapy for sepsis. Because the induction of anti-inflammatory macrophages by microRNA (miR), a regulator of mRNA, has been mentioned, the exploration on miR-induced anti-inflammatory macrophages was performed. The over-expression of miR-223 and miR-146a in RAW264.7 induced M2 macrophage-polarization (anti-inflammatory macrophages) as evaluated by the enhanced expression of Arginase-1 and Fizz. However, miR-223 over-expressed cells demonstrated the more potent anti-inflammatory property against LPS stimulation as lesser iNOS expression, lower supernatant IL-6 and higher supernatant IL-10 compared with miR-146a over-expressed cells. Interestingly, LPS stimulation in miR-223 over-expressed cells, compared with LPS-stimulated control cells, demonstrated lower activity of glycolysis pathway and higher mitochondrial respiration, as evaluated by the extracellular flux analysis, and also down-regulated HIF-1α, an important enzyme of glycolysis pathway. In addition, the administration of miR-223 over-expressed macrophages with IL-4 pre-conditioning, but not IL-4 stimulated control cells, attenuated sepsis severity in LPS injected mice as evaluated by serum creatinine, liver enzymes, lung histology and serum cytokines. In conclusion, miR-223 interfered with the glycolysis pathway through the down-regulation of HIF-1α, resulting in the anti-inflammatory status. The over-expression of miR-223 in macrophages prevented the conversion into M1 macrophage polarization after LPS stimulation. The administration of miR-223 over-expressed macrophages, with IL-4 preconditioning, attenuated sepsis severity in LPS model. Hence, a proof of concept in the induction of anti-inflammatory macrophages through the cell-energy interference for sepsis treatment was proposed as a basis of cell-based therapy in sepsis.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Glicólise , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Macrófagos/transplante , MicroRNAs/genética , Sepse/prevenção & controle , Animais , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Ativação de Macrófagos , Macrófagos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sepse/induzido quimicamente , Sepse/metabolismo , Sepse/patologia
17.
Angiol Sosud Khir ; 26(2): 23-33, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32597882

RESUMO

BACKGROUND: Cell therapy was proposed as a procedure of indirect revascularization for patients with critical ischaemia of lower extremities for whom endovascular and surgical revascularization is impossible. We present herein a review of the state of the art of studies in the field of cell therapy of this cohort of patients. BASIC PROVISIONS: Cell therapy has proved safe, however, the results of studies of efficacy are relatively ambiguous and unconvincing. The number of patients in separately taken clinical trials is minimal. The reviewed studies differed not only by heterogeneity of the cell types used but by the routes of administration of cells (cells were delivered either intramuscularly (predominantly) or intraarterially) and the duration of follow up (time of assessment and duration of follow up varied from 1 month to 2 years). One of the problems became the lack of the routine study of the angiogenic potential of stem cells prior to their clinical application. It is known that the angiogenic activity of multipotent cells of apparently healthy patients may differ from that of patients suffering from atherosclerosis, chronic renal failure, diabetes. CONCLUSIONS: It is supposed that treatment with stem cells or precursor cells is more efficient as compared to protein or gene therapy not only owing to direct vasculogenic properties but a paracrine action through excretion of proangiogenic biologically active substances. More studies with larger cohorts are necessary to provide stronger safety and efficacy data on cell therapy. Besides, a promising trend in the field of cellular approaches is modulation of regenerative capability of stem cells, which may help overcome difficulties in understanding the place of cell therapy in therapeutic angiogenesis.


Assuntos
Isquemia/terapia , Extremidade Inferior , Terapia Baseada em Transplante de Células e Tecidos , Terapia Genética , Humanos , Células-Tronco
18.
Nat Commun ; 11(1): 2758, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488069

RESUMO

Human beige adipocytes (BAs) have potential utility for the development of therapeutics to treat diabetes and obesity-associated diseases. Although several reports have described the generation of beige adipocytes in vitro, their potential utility in cell therapy and drug discovery has not been reported. Here, we describe the generation of BAs from human adipose-derived stem/stromal cells (ADSCs) in serum-free medium with efficiencies >90%. Molecular profiling of beige adipocytes shows them to be similar to primary BAs isolated from human tissue. In vitro, beige adipocytes exhibit uncoupled mitochondrial respiration and cAMP-induced lipolytic activity. Following transplantation, BAs increase whole-body energy expenditure and oxygen consumption, while reducing body-weight in recipient mice. Finally, we show the therapeutic utility of BAs in a platform for high-throughput drug screening (HTS). These findings demonstrate the potential utility of BAs as a cell therapeutic and as a tool for the identification of drugs to treat metabolic diseases.


Assuntos
Adipócitos Bege/metabolismo , Terapia Baseada em Transplante de Células e Tecidos/métodos , Descoberta de Drogas/métodos , Doenças Metabólicas/metabolismo , Adipócitos Bege/citologia , Animais , Peso Corporal , Avaliação Pré-Clínica de Medicamentos , Metabolismo Energético , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Masculino , Células-Tronco Mesenquimais , Doenças Metabólicas/tratamento farmacológico , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mitocôndrias/metabolismo , Consumo de Oxigênio , Células Estromais , Transplante
19.
Front Immunol ; 11: 1091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574263

RESUMO

Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. There is no approved effective therapy for COVID-19, but MSC therapies have shown first promise in the treatment of acute respiratory distress syndrome (ARDS) pneumonia, inflammation, and sepsis, which are among the leading causes of mortality in COVID-19 patients. Many of the critically ill COVID-19 patients are in a hypercoagulable procoagulant state and at high risk for disseminated intravascular coagulation, thromboembolism, and thrombotic multi-organ failure, another cause of high fatality. It is not yet clear whether IV infusion is a safe and effective route of MSC delivery in COVID-19, since MSC-based products express variable levels of highly procoagulant tissue factor (TF/CD142), compromising the cells' hemocompatibility and safety profile. Of concern, IV infusions of poorly characterized MSC products with unchecked (high) TF/CD142 expression could trigger blood clotting in COVID-19 and other vulnerable patient populations and further promote the risk for thromboembolism. In contrast, well-characterized products with robust manufacturing procedures and optimized modes of clinical delivery hold great promise for ameliorating COVID-19 by exerting their beneficial immunomodulatory effects, inducing tissue repair and organ protection. While the need for MSC therapy in COVID-19 is apparent, integrating both innate and adaptive immune compatibility testing into the current guidelines for cell, tissue, and organ transplantation is critical for safe and effective therapies. It is paramount to only use well-characterized, safe MSCs even in the most urgent and experimental treatments. We here propose three steps to mitigate the risk for these vulnerable patients: (1) updated clinical guidelines for cell and tissue transplantation, (2) updated minimal criteria for characterization of cellular therapeutics, and (3) updated cell therapy routines reflecting specific patient needs.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Imunologia de Transplantes , Administração Intravenosa , Transtornos da Coagulação Sanguínea/etiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Guias como Assunto , Humanos , Injeções Intramusculares , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia
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