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2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
PLoS One ; 15(6): e0234441, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525941

RESUMO

Human iPSC-derived hepatocytes hold great promise as a cell source for cell therapy and drug screening. However, the culture method for highly-quantified hepatocytes has not yet been established. Herein, we have developed an encapsulation and 3D cultivation method for iPSC-hepatocytes in core-shell hydrogel microfibers (a.k.a. cell fiber). In the fiber-shaped 3D microenvironment consisting of abundant extracellular matrix (ECM), the iPSC-hepatocytes exhibited many hepatic characteristics, including the albumin secretion, and the expression of the hepatic marker genes (ALB, HNF4α, ASGPR1, CYP2C19, and CYP3A4). Furthermore, we found that the fibers were mechanically stable and can be applicable to hepatocyte transplantation. Three days after transplantation of the microfibers into the abdominal cavity of immunodeficient mice, human albumin was detected in the peripheral blood of the transplanted mice. These results indicate that the iPSC-hepatocyte fibers are promising either as in vitro models for drug screening or as implantation grafts to treat liver failure.


Assuntos
Técnicas de Cultura de Células/métodos , Encapsulamento de Células/métodos , Hepatócitos/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Cavidade Abdominal/cirurgia , Alginatos/química , Animais , Técnicas de Cultura de Células/instrumentação , Diferenciação Celular , Encapsulamento de Células/instrumentação , Terapia Baseada em Transplante de Células e Tecidos/métodos , Perfilação da Expressão Gênica , Hepatócitos/transplante , Humanos , Hidrogéis/química , Falência Hepática/terapia , Masculino , Camundongos , Esferoides Celulares
9.
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
10.
Medicine (Baltimore) ; 99(26): e20788, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590759

RESUMO

BACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia. METHODS/DESIGN: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy. DISCUSSION: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials (http://jrct.niph.go.jp) as jRCTb070190057.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Leucócitos Mononucleares/transplante , Lesões por Radiação , Glândulas Salivares , Xerostomia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Imagem por Ressonância Magnética/métodos , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/fisiopatologia , Lesões por Radiação/terapia , Projetos de Pesquisa , Glândulas Salivares/diagnóstico por imagem , Glândulas Salivares/patologia , Glândulas Salivares/fisiopatologia , Glândulas Salivares/efeitos da radiação , Tomografia Computadorizada por Raios X/métodos , Transplante Autólogo/métodos , Resultado do Tratamento , Xerostomia/diagnóstico , Xerostomia/etiologia , Xerostomia/fisiopatologia , Xerostomia/terapia
11.
Am J Respir Cell Mol Biol ; 63(3): 374-385, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32437238

RESUMO

Cystic fibrosis (CF) is caused by loss-of-function mutations in the CFTR (CF transmembrane regulator) gene. Pharmacologic therapies directed at CFTR have been developed but are not effective for mutations that result in little or no mRNA or protein expression. Cell therapy is a potential mutation-agnostic approach to treatment. One strategy is to harvest human bronchial epithelial cells (HBECs) for gene addition or genetic correction, followed by expansion and engraftment. This approach will require cells to grow extensively while retaining their ability to reconstitute CFTR activity. We hypothesized that conditionally reprogrammed cell (CRC) technology, namely growth in the presence of irradiated feeder cells and a Rho kinase inhibitor, would enable expansion while maintaining cell capacity to express functional CFTR. Our goal was to compare expression of the basal cell marker NGFR (nerve growth factor receptor) and three-dimensional bronchosphere colony-forming efficiency (CFE) in early- and later-passage HBECs grown using nonproprietary bronchial epithelial growth medium or the CRC method. Cell number and CFTR activity were determined in a competitive repopulation assay employing chimeric air-liquid interface cultures. HBECs expanded using the CRC method expressed the highest NGFR levels, had the greatest 3D colony-forming efficiency at later passage, generated greater cell numbers in chimeric cultures, and most effectively reconstituted CFTR activity. In our study, the HBEC air-liquid interface model, an informative testing platform proven vital for the development of other CF therapies, illustrated that cells grown by CRC technology or equivalent methods may be useful for cell therapy of CF.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/metabolismo , Células Epiteliais/metabolismo , Brônquios/metabolismo , Terapia Baseada em Transplante de Células e Tecidos/métodos , Humanos , Células-Tronco/citologia
12.
Clin Microbiol Infect ; 26(8): 988-998, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32454187

RESUMO

BACKGROUND: As COVID-19 cases continue to rise globally, evidence from large randomized controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are being undertaken all over the world. OBJECTIVES: We summarized all registered clinical trials examining treatment and prevention options for COVID-19. Additionally, we evaluated the quality of the retrieved studies. DATA SOURCES: Clinicaltrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. STUDY ELIGIBILITY CRITERIA: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. We excluded withdrawn or cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19. PARTICIPANTS AND INTERVENTIONS: No restrictions in terms of participants' age and medical background or type of intervention were enforced. METHODS: The registries were searched using the term 'coronavirus' or 'COVID-19' from their inception until 26 March 2020. Additional manual search of the registries was also performed. Eligible studies were summarized and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing traditional Chinese medicine. RESULTS: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and three studies examining both were retrieved. Finally, 214 studies were methodologically reviewed. Interventional treatment studies were mostly randomized (n = 150/198, 76%) and open label (n = 73/198, 37%) with a median number of planned inclusions of 90 (interquartile range 40-200). Major categories of interventions that are currently being investigated are discussed. CONCLUSIONS: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarized data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Antivirais/farmacologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Stem Cells Transl Med ; 9(9): 1007-1022, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32472653

RESUMO

Severe cases of COVID-19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID-19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo-capillary barriers. The authors performed a systematic literature review and random-effects meta-analysis to determine the potential value of MSC therapy for treating COVID-19-infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO2 /FiO2 ratio, alveolo-capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/terapia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Pulmão/fisiologia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Síndrome do Desconforto Respiratório do Adulto/virologia
15.
Lancet ; 395(10237): 1627-1639, 2020 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-32446407

RESUMO

BACKGROUND: Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment. METHODS: The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered with ClinicalTrials.gov, NCT01656135, NCT02252055, NCT02085629, NCT02244801, NCT02371434, NCT02129881, and NCT02091232. FINDINGS: The seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3·2-18·0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT. INTERPRETATION: Regulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression. FUNDING: The 7th EU Framework Programme.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Rejeição de Enxerto/prevenção & controle , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Células Dendríticas/imunologia , Rejeição de Enxerto/imunologia , Humanos , Imunossupressão/efeitos adversos , Macrófagos/imunologia , Linfócitos T Reguladores/imunologia
16.
Biol Blood Marrow Transplant ; 26(6): 1043-1049, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-93849

RESUMO

The coronavirus-19 (COVID-19) pandemic poses a significant risk to patients undergoing hematopoietic stem cell transplantation (HCT) or cellular therapy. The American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Steering Committee aims to provide pharmacy practice management recommendations for how to transition clinical HCT or cellular therapy pharmacy services using telemedicine capabilities in the inpatient and outpatient settings to maintain an equivalent level of clinical practice while minimizing viral spread in a high-risk, immunocompromised population. In addition, the Steering Committee offers clinical management recommendations for COVID-19 in HCT and cellular therapy recipients based on the rapidly developing literature. As the therapeutic and supportive care interventions for COVID-19 expand, collaboration with clinical pharmacy providers is critical to ensure safe administration in HCT recipients. Attention to drug-drug interactions (DDIs) and toxicity, particularly QTc prolongation, warrants close cardiac monitoring and potential cessation of concomitant QTc-prolonging agents. Expanded indications for hydroxychloroquine and tocilizumab have already caused stress on the usual supply chain. Detailed prescribing algorithms, decision pathways, and specific patient population stock may be necessary. The COVID-19 pandemic has challenged all members of the healthcare team, and we must continue to remain vigilant in providing pharmacy clinical services to one of the most high-risk patient populations while also remaining committed to providing compassionate and safe care for patients undergoing HCT and cellular therapies.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Gerenciamento Clínico , Transplante de Células-Tronco Hematopoéticas , Pandemias , Serviço de Farmácia Hospitalar/organização & administração , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Betacoronavirus/patogenicidade , Terapia Baseada em Transplante de Células e Tecidos/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Pacientes Internados , Pacientes Ambulatoriais , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/genética , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/estatística & dados numéricos , Opinião Pública , Sociedades Médicas , Telemedicina/métodos , Estados Unidos/epidemiologia
17.
Biol Blood Marrow Transplant ; 26(6): 1043-1049, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-72438

RESUMO

The coronavirus-19 (COVID-19) pandemic poses a significant risk to patients undergoing hematopoietic stem cell transplantation (HCT) or cellular therapy. The American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Steering Committee aims to provide pharmacy practice management recommendations for how to transition clinical HCT or cellular therapy pharmacy services using telemedicine capabilities in the inpatient and outpatient settings to maintain an equivalent level of clinical practice while minimizing viral spread in a high-risk, immunocompromised population. In addition, the Steering Committee offers clinical management recommendations for COVID-19 in HCT and cellular therapy recipients based on the rapidly developing literature. As the therapeutic and supportive care interventions for COVID-19 expand, collaboration with clinical pharmacy providers is critical to ensure safe administration in HCT recipients. Attention to drug-drug interactions (DDIs) and toxicity, particularly QTc prolongation, warrants close cardiac monitoring and potential cessation of concomitant QTc-prolonging agents. Expanded indications for hydroxychloroquine and tocilizumab have already caused stress on the usual supply chain. Detailed prescribing algorithms, decision pathways, and specific patient population stock may be necessary. The COVID-19 pandemic has challenged all members of the healthcare team, and we must continue to remain vigilant in providing pharmacy clinical services to one of the most high-risk patient populations while also remaining committed to providing compassionate and safe care for patients undergoing HCT and cellular therapies.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Gerenciamento Clínico , Transplante de Células-Tronco Hematopoéticas , Pandemias , Serviço de Farmácia Hospitalar/organização & administração , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Betacoronavirus/patogenicidade , Terapia Baseada em Transplante de Células e Tecidos/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Pacientes Internados , Pacientes Ambulatoriais , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/genética , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/estatística & dados numéricos , Opinião Pública , Sociedades Médicas , Telemedicina/métodos , Estados Unidos/epidemiologia
18.
Stem Cells Dev ; 29(11): 679-681, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: covidwho-60278

RESUMO

The novel coronavirus disease 2019 (COVID-19) has grown to be a global public-health emergency since patients were first detected in Wuhan, China, in December 2019. As of April 9, 2020, the novel coronavirus (named as SARS-CoV-2 by the International Committee on Taxonomy of Viruses on February 11) has infected 83,251 and 1,484,811 patients in China and the world, respectively. However, we have neither confirmed effective antiviral medications nor vaccines available to deal with this emergency. In this commentary, we offer an alternative promising therapy for COVID-19, that is, mesenchymal stem cell transplantation.


Assuntos
Betacoronavirus/imunologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Infecções por Coronavirus/terapia , Células Dendríticas/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Diferenciação Celular/fisiologia , Células Dendríticas/citologia , Humanos , Células-Tronco Mesenquimais/citologia , Pandemias
19.
J Vis Exp ; (157)2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32281978

RESUMO

Many current therapeutics under development for diseases of the posterior pole of the eye are biologics. These drugs need to be administered frequently, typically via intravitreal injections. Encapsulated cells expressing the biologic of choice are becoming a tool for local protein production and release (e.g., via long-term drug delivery). In addition, encapsulation systems utilize permeable materials that allow diffusion of nutrients, waste, and therapeutic factors into and out of cells. This occurs while masking the cells from the host immune response, avoiding the need for suppression of the host immune system. This protocol describes the use of alginate as a polymer in microencapsulation coupled with the electrospray method as a microencapsulation technique. ARPE-19 cells, a spontaneously arising human RPE cell line, has been used in long-term cell therapy experiments due to its lifetime functionality, and it is used here for encapsulation and delivery of the capsules to mouse eyes. The manuscript summarizes the steps for cell microencapsulation, quality control, and ocular delivery.


Assuntos
Produtos Biológicos/química , Terapia Baseada em Transplante de Células e Tecidos/métodos , Sistemas de Liberação de Medicamentos/métodos , Olho/efeitos dos fármacos , Animais , Cápsulas , Modelos Animais de Doenças , Camundongos
20.
Biol Blood Marrow Transplant ; 26(6): 1043-1049, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32305359

RESUMO

The coronavirus-19 (COVID-19) pandemic poses a significant risk to patients undergoing hematopoietic stem cell transplantation (HCT) or cellular therapy. The American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Steering Committee aims to provide pharmacy practice management recommendations for how to transition clinical HCT or cellular therapy pharmacy services using telemedicine capabilities in the inpatient and outpatient settings to maintain an equivalent level of clinical practice while minimizing viral spread in a high-risk, immunocompromised population. In addition, the Steering Committee offers clinical management recommendations for COVID-19 in HCT and cellular therapy recipients based on the rapidly developing literature. As the therapeutic and supportive care interventions for COVID-19 expand, collaboration with clinical pharmacy providers is critical to ensure safe administration in HCT recipients. Attention to drug-drug interactions (DDIs) and toxicity, particularly QTc prolongation, warrants close cardiac monitoring and potential cessation of concomitant QTc-prolonging agents. Expanded indications for hydroxychloroquine and tocilizumab have already caused stress on the usual supply chain. Detailed prescribing algorithms, decision pathways, and specific patient population stock may be necessary. The COVID-19 pandemic has challenged all members of the healthcare team, and we must continue to remain vigilant in providing pharmacy clinical services to one of the most high-risk patient populations while also remaining committed to providing compassionate and safe care for patients undergoing HCT and cellular therapies.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Gerenciamento Clínico , Transplante de Células-Tronco Hematopoéticas , Pandemias , Serviço de Farmácia Hospitalar/organização & administração , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Betacoronavirus/patogenicidade , Terapia Baseada em Transplante de Células e Tecidos/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Pacientes Internados , Pacientes Ambulatoriais , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/genética , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/estatística & dados numéricos , Opinião Pública , Sociedades Médicas , Telemedicina/métodos , Estados Unidos/epidemiologia
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