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1.
Medicine (Baltimore) ; 99(43): e22927, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120849

RESUMO

RATIONALE: Hepatic sinusoidal obstruction syndrome (SOS) is a rare and potentially fatal complications after hematopoietic stem cell transplantation (HSCT). Most severe SOS result in multi-organ dysfunction and are associated with a high mortality rate (>80%). PATIENT CONCERNS: A 31-year-old man was diagnosed with chronic myeloid leukemia blast crisis. He presented with severe thrombocytopenia on day 42 post-HSCT (on days +42), gradually developed with painful hepatomegaly, ascites, and weight gain. DIAGNOSES: The abdominal computerized tomography showed hepatomegaly, hepatic congestion, periportal edema, narrow hepatic vein, and ascites suggestive of SOS/hepatic vein occlusion. According to the EBMT revised diagnostic criteria, the patient was diagnosed as late-onset severe SOS. INTERVENTIONS: Comprehensive treatment including low molecular weight heparin was initiated. OUTCOMES: The patient had good response with resolution of his hepatomegaly, increase of platelet, weight and transaminase loss after 4 weeks treatment. LESSONS: In SOS patients with nonspecific clinical and biochemical findings, computerized tomography scans can be useful in differentiating SOS from other complications after HSCT. low molecular weight heparin is effective for the treatment of SOS.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/etiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Adulto , Anticoagulantes/uso terapêutico , Ascite/etiologia , Heparina de Baixo Peso Molecular/uso terapêutico , Hepatopatia Veno-Oclusiva/diagnóstico por imagem , Hepatomegalia/etiologia , Humanos , Masculino , Índice de Gravidade de Doença , Transplante de Células-Tronco/métodos , Trombocitopenia/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
3.
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
4.
Nat Commun ; 11(1): 3369, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632153

RESUMO

Induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neurons are an expected source for cell-based therapies for Parkinson's disease (PD). The regulatory criteria for the clinical application of these therapies, however, have not been established. Here we show the results of our pre-clinical study, in which we evaluate the safety and efficacy of dopaminergic progenitors (DAPs) derived from a clinical-grade human iPSC line. We confirm the characteristics of DAPs by in vitro analyses. We also verify that the DAP population include no residual undifferentiated iPSCs or early neural stem cells and have no genetic aberration in cancer-related genes. Furthermore, in vivo studies using immunodeficient mice reveal no tumorigenicity or toxicity of the cells. When the DAPs are transplanted into the striatum of 6-OHDA-lesioned rats, the animals show behavioral improvement. Based on these results, we started a clinical trial to treat PD patients in 2018.


Assuntos
Neurônios Dopaminérgicos/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Neurais/transplante , Doença de Parkinson/terapia , Transplante de Células-Tronco/métodos , Animais , Diferenciação Celular/genética , Linhagem Celular , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Macaca fascicularis , Masculino , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Ratos Nus , Transplante Heterólogo
5.
Nat Rev Drug Discov ; 19(7): 463-479, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32612263

RESUMO

Naturally occurring stem cells isolated from humans have been used therapeutically for decades. This has primarily involved the transplantation of primary cells such as haematopoietic and mesenchymal stem cells and, more recently, derivatives of pluripotent stem cells. However, the advent of cell-engineering approaches is ushering in a new generation of stem cell-based therapies, greatly expanding their therapeutic utility. These next-generation stem cells are being used as 'Trojan horses' to improve the delivery of drugs and oncolytic viruses to intractable tumours and are also being engineered with angiogenic, neurotrophic and anti-inflammatory molecules to accelerate the repair of injured or diseased tissues. Moreover, gene therapy and gene editing technologies are being used to create stem cell derivatives with improved functionality, specificity and responsiveness compared with their natural counterparts. Here, we review these engineering approaches and areas in which they will help broaden the utility and clinical applicability of stem cells.


Assuntos
Engenharia Celular/métodos , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Animais , Sistemas de Liberação de Medicamentos , Edição de Genes , Terapia Genética/métodos , Humanos , Terapia Viral Oncolítica/métodos
6.
Life Sci ; 257: 118091, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32668325

RESUMO

AIM: Inflammatory and oxidative microenvironment at diabetic' wound site hinder the therapeutic efficacy of cell-based therapies in diabetic patients. The purpose of this study is to explore the competence of curcumin preconditioned human adipose derived cells (hASCs) in combination with platelet rich plasma (PRP) for the repair of wounds in diabetic rats. MAIN METHODS: The cytoprotective effect of curcumin preconditioning for hASCs against hyperglycemic stress was evaluated through analysis of cell morphology, viability, cytotoxicity, senescence, and scratch wound healing assays. Subsequently, the healing capacity of curcumin preconditioned hASCs (Cur-hASCs) added to PRP was examined in excisional wounded diabetic rat model. Healed skin biopsies were excised to analyze gene and protein expression of wound healing markers by qPCR and western blotting. Histopathological changes were observed through hematoxylin and eosin staining. KEY FINDINGS: We found that Cur-hASCs counteract the glucose stress much better than non-preconditioned hASCs by maintaining their cellular morphology and viability as well as metabolic potential. Further in vivo results revealed that, Cur-hASCs co-injected with PRP resulted in faster wound closure, improved fibroblast proliferation, increased neovascularization, marked reduction in inflammatory cells, and compact extracellular matrix with completely covered thick epithelium. Moreover, Cur-hASCs + PRP treatment significantly improved the expression of key healing markers such as pro-angiogenic (Vegf), dermal matrix deposition (Col1α1), cell migration (bFgf) and cell proliferation (Pcna) at wound site. SIGNIFICANCE: Our findings propose a combinatorial therapy (Cur-hASCs + PRP) as a novel modality to improve the efficacy of hASCs-based therapy for diabetic wounds.


Assuntos
Curcumina/farmacologia , Diabetes Mellitus Experimental/terapia , Plasma Rico em Plaquetas , Transplante de Células-Tronco/métodos , Cicatrização/fisiologia , Tecido Adiposo/citologia , Animais , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Terapia Combinada , Diabetes Mellitus Experimental/complicações , Feminino , Glucose/metabolismo , Humanos , Ratos , Ratos Wistar
7.
J Vis Exp ; (160)2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32658201

RESUMO

Neural stem cell (NSC) therapy is an emerging innovative treatment for stroke, traumatic brain injury and neurodegenerative disorders. As compared to intracranial delivery, intra-arterial administration of NSCs is less invasive and produces a more diffuse distribution of NSCs within the brain parenchyma. Further, intra-arterial delivery allows the first-pass effect in the brain circulation, lessening the potential for trapping of cells in peripheral organs, such as liver and spleen, a complication associated with peripheral injections. Here, we detail the methodology, in both mice and rats, for delivery of NSCs through the common carotid artery (mouse) or external carotid artery (rat) to the ipsilateral hemisphere after an ischemic stroke. Using GFP-labeled NSCs, we illustrate the widespread distribution achieved throughout the rodent ipsilateral hemisphere at 1 d, 1 week and 4 weeks after postischemic delivery, with a higher density in or near the ischemic injury site. In addition to long-term survival, we show evidence of differentiation of GFP-labeled cells at 4 weeks. The intra-arterial delivery approach described here for NSCs can also be used for administration of therapeutic compounds, and thus has broad applicability to varied CNS injury and disease models across multiple species.


Assuntos
Isquemia Encefálica/cirurgia , Injeções Intra-Arteriais/métodos , Células-Tronco Neurais/metabolismo , Transplante de Células-Tronco/métodos , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Células-Tronco Neurais/citologia , Ratos , Ratos Wistar
9.
Trials ; 21(1): 520, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: covidwho-595058

RESUMO

OBJECTIVES: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. TRIAL DESIGN: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. PARTICIPANTS: Twenty serious COVID-19 cases will be enrolled in the trial from April 6th to December 31st 2020. INCLUSION CRITERIA: hospitalised patients at Renmin Hospital of Wuhan University satisfy all criteria as below: 1)Adults aged 18-65 years;2)Voluntarily participate in this clinical trial and sign the "informed consent form" or have consent from a legal representative.3)Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg).4)COVID-19 featured lung lesions in chest X-ray image. EXCLUSION CRITERIA: Patients will be excluded from the study if they meet any of the following criteria. 1.Patients have received other experimental treatment for COVID-19 within the last 30 days;2.Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);3.Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;4.Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;5.Female patients who have no sexual protection in the last 30 days prior to the screening assessment;6.Pregnant or lactating women or women using estrogen contraception;7.Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;8.Other conditions that the researchers consider not suitable for participating in this clinical trial. INTERVENTION AND COMPARATOR: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x107 human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. MAIN OUTCOMES: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: GradeDescriptionGrade 1:Discharged of patient;Grade 2:Hospitalized without oxygen supplement;Grade 3:Hospitalized, oxygen supplement is required, but NIV / HFNC is not required;Grade 4:Hospitalized in intensive care unit, and NIV / HFNC treatment is required;Grade 5:Hospitalized in intensive care unit, requiring ECMO and/or IMV;Grade 6:Death. ABBREVIATIONS: NIV, non-invasive mechanical ventilation; HFNC, high-flow nasal catheter; IMV, invasive mechanical ventilation. 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h ± 30min, 24h ± 30min after the injection) and follow-up period D90 ± 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h ± 30min, 24h ± 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 ± 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 ± 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 ß, IL-2, TNF-a, ITN-γ), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood ß-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 ± 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h ± 30min after the injection and not detected after discharge). RANDOMIZATION: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. BLINDING (MASKING): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient's randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Twenty participants will be randomized to the experimental and control groups (10 per group). TRIAL STATUS: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16th April and an estimated date of the recruitment of the final participants will be around end of July. . TRIAL REGISTRATION: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Infecções por Coronavirus/terapia , Polpa Dentária/citologia , Pneumonia Viral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Betacoronavirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo , Adulto Jovem
10.
Trials ; 21(1): 520, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532356

RESUMO

OBJECTIVES: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. TRIAL DESIGN: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. PARTICIPANTS: Twenty serious COVID-19 cases will be enrolled in the trial from April 6th to December 31st 2020. INCLUSION CRITERIA: hospitalised patients at Renmin Hospital of Wuhan University satisfy all criteria as below: 1)Adults aged 18-65 years;2)Voluntarily participate in this clinical trial and sign the "informed consent form" or have consent from a legal representative.3)Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg).4)COVID-19 featured lung lesions in chest X-ray image. EXCLUSION CRITERIA: Patients will be excluded from the study if they meet any of the following criteria. 1.Patients have received other experimental treatment for COVID-19 within the last 30 days;2.Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);3.Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;4.Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;5.Female patients who have no sexual protection in the last 30 days prior to the screening assessment;6.Pregnant or lactating women or women using estrogen contraception;7.Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;8.Other conditions that the researchers consider not suitable for participating in this clinical trial. INTERVENTION AND COMPARATOR: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x107 human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. MAIN OUTCOMES: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: GradeDescriptionGrade 1:Discharged of patient;Grade 2:Hospitalized without oxygen supplement;Grade 3:Hospitalized, oxygen supplement is required, but NIV / HFNC is not required;Grade 4:Hospitalized in intensive care unit, and NIV / HFNC treatment is required;Grade 5:Hospitalized in intensive care unit, requiring ECMO and/or IMV;Grade 6:Death. ABBREVIATIONS: NIV, non-invasive mechanical ventilation; HFNC, high-flow nasal catheter; IMV, invasive mechanical ventilation. 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h ± 30min, 24h ± 30min after the injection) and follow-up period D90 ± 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h ± 30min, 24h ± 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 ± 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 ± 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 ß, IL-2, TNF-a, ITN-γ), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood ß-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 ± 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h ± 30min after the injection and not detected after discharge). RANDOMIZATION: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. BLINDING (MASKING): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient's randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Twenty participants will be randomized to the experimental and control groups (10 per group). TRIAL STATUS: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16th April and an estimated date of the recruitment of the final participants will be around end of July. . TRIAL REGISTRATION: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Infecções por Coronavirus/terapia , Polpa Dentária/citologia , Pneumonia Viral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Betacoronavirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo , Adulto Jovem
11.
Medicine (Baltimore) ; 99(22): e20395, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481428

RESUMO

RATIONALE: Autologous stem cell transplantation (ASCT) is not routinely recommended as first-line choice for follicular lymphoma (FL). However, we actually have observed that young patients with extremely high-risk factors benefit from ASCT. This study aims to speculate the rationality of ASCT as first-line treatment, through 3 cases and review of the literature. PATIENT CONCERNS: 3 young-adult patients with FL received ASCT as first-line treatment. DIAGNOSIS: All the 3 patients were no more than 30 years old and the diagnosis of FL was confirmed by histopathological and immunohistochemical evaluations. They all had multi-organ involvements, and two of them presented with a "leukemic-like" manifestation. Compared with those in the previous literatures, the 3 patients were relatively younger and had more invasive clinical features. INTERVENTIONS: The 3 patients received combined chemotherapy plus rituximab, followed by first-line ASCT. OUTCOMES: All the 3 patients got complete remission and minimal residual disease negativity after ASCT, The median follow-up time was 109 (97-117) months, and all of them were in remission more than 8 years after transplant. LESSONS: Guidelines for FL are mainly based on elderly patients, but are not suitable enough for all, especially for the young FL patients. For young patients with certain high-risk FL, first-line ASCT does not go against the guidelines, and should be recommended individually.


Assuntos
Linfoma Folicular/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Humanos , Masculino , Indução de Remissão , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Transplante de Células-Tronco/métodos , Transplante Autólogo , Adulto Jovem
12.
Nat Commun ; 11(1): 2687, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483116

RESUMO

Injury of corpus cavernosa results in erectile dysfunction, but its treatment has been very difficult. Here we construct heparin-coated 3D-printed hydrogel scaffolds seeded with hypoxia inducible factor-1α (HIF-1α)-mutated muscle-derived stem cells (MDSCs) to develop bioengineered vascularized corpora. HIF-1α-mutated MDSCs significantly secrete various angiogenic factors in MDSCs regardless of hypoxia or normoxia. The biodegradable scaffolds, along with MDSCs, are implanted into corpus cavernosa defects in a rabbit model to show good histocompatibility with no immunological rejection, support vascularized tissue ingrowth, and promote neovascularisation to repair the defects. Evaluation of morphology, intracavernosal pressure, elasticity and shrinkage of repaired cavernous tissue prove that the bioengineered corpora scaffolds repair the defects and recover penile erectile and ejaculation function successfully. The function recovery restores the reproductive capability of the injured male rabbits. Our work demonstrates that the 3D-printed hydrogels with angiogenic cells hold great promise for penile reconstruction to restore reproductive capability of males.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Pênis/lesões , Transplante de Células-Tronco/métodos , Animais , Sobrevivência Celular , Modelos Animais de Doenças , Disfunção Erétil/diagnóstico por imagem , Disfunção Erétil/fisiopatologia , Disfunção Erétil/cirurgia , Feminino , Heparina , Humanos , Hidrogéis , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Nus , Proteínas Mutantes/genética , Neovascularização Fisiológica , Pênis/irrigação sanguínea , Pênis/fisiopatologia , Gravidez , Impressão Tridimensional , Coelhos , Tecidos Suporte , Transfecção
13.
Nat Commun ; 11(1): 2713, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483127

RESUMO

Despite their rapidly-expanding therapeutic potential, human pluripotent stem cell (hPSC)-derived cell therapies continue to have serious safety risks. Transplantation of hPSC-derived cell populations into preclinical models has generated teratomas (tumors arising from undifferentiated hPSCs), unwanted tissues, and other types of adverse events. Mitigating these risks is important to increase the safety of such therapies. Here we use genome editing to engineer a general platform to improve the safety of future hPSC-derived cell transplantation therapies. Specifically, we develop hPSC lines bearing two drug-inducible safeguards, which have distinct functionalities and address separate safety concerns. In vitro administration of one small molecule depletes undifferentiated hPSCs >106-fold, thus preventing teratoma formation in vivo. Administration of a second small molecule kills all hPSC-derived cell-types, thus providing an option to eliminate the entire hPSC-derived cell product in vivo if adverse events arise. These orthogonal safety switches address major safety concerns with pluripotent cell-derived therapies.


Assuntos
Técnicas de Cultura de Células/métodos , Diferenciação Celular/genética , Edição de Genes/métodos , Células-Tronco Pluripotentes/metabolismo , Transplante de Células-Tronco/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Tacrolimo/análogos & derivados , Tacrolimo/farmacologia , Teratoma/genética , Teratoma/metabolismo , Teratoma/prevenção & controle
14.
Cell Stem Cell ; 26(6): 806-810, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: covidwho-526598

RESUMO

In the midst of a global public health emergency, some businesses are taking advantage of widespread fears by marketing purported stem cell treatments for COVID-19. Such businesses target prospective clients with misleading claims, expose patients to potentially risky stem cell-based products, and undermine efforts to develop evidence-based treatments for COVID-19.


Assuntos
Infecções por Coronavirus/psicologia , Marketing , Pneumonia Viral/psicologia , Transplante de Células-Tronco/métodos , Betacoronavirus , Comércio , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Medo , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Transplante de Células-Tronco/economia
15.
Intern Med J ; 50(6): 667-679, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-271531

RESUMO

The COVID-19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID-19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID-19, including the use of telehealth, avoidance of non-essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy-associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID-19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID-19 and available local healthcare resources.


Assuntos
Consenso , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Controle de Infecções/métodos , Leucemia Linfocítica Crônica de Células B/fisiopatologia , Linfoma/fisiopatologia , Mieloma Múltiplo/fisiopatologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Austrália , Betacoronavirus/imunologia , Comorbidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Tratamento Farmacológico , Fidelidade a Diretrizes , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma/imunologia , Linfoma/terapia , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Nova Zelândia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Guias de Prática Clínica como Assunto , Medição de Risco , Terapia de Salvação/métodos , Transplante de Células-Tronco/métodos
17.
Life Sci ; 254: 117766, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32418895

RESUMO

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common critical disease which can be caused by multiple pathological factors in clinic. However, feasible and effective treatment strategies of ALI/ARDS are limited. At present, the beneficial effect of stem cells (SCs)-based therapeutic strategies for ALI/ARDS can be attributed to paracrine. Exosomes, as a paracrine product, are regarded as a critical regulatory mediator. Furthermore, substantial evidence has indicated that exosomes from SCs can transmit bioactive components including genetic material and protein to the recipient cells and provide a protective effect. The protective role is played through a series of process including inflammation modulation, the reconstruction of alveolar epithelium and endothelium, and pulmonary fibrosis prevention. Therefore, SCs derived exosomes have the potential to be used for therapeutic strategies for ALI/ARDS. In this review, we discuss the present understanding of SCs derived exosomes related to ALI/ARDS and provide insights for developing a cell-free strategy for treating ALI/ARDS.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Exossomos/transplante , Síndrome do Desconforto Respiratório do Adulto/terapia , Lesão Pulmonar Aguda/metabolismo , Células Epiteliais Alveolares/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Dispneia , Endotélio/metabolismo , Exossomos/metabolismo , Humanos , Inflamação , Síndrome do Desconforto Respiratório do Adulto/patologia , Transplante de Células-Tronco/métodos , Células-Tronco/metabolismo
18.
Cell Stem Cell ; 26(6): 806-810, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32464095

RESUMO

In the midst of a global public health emergency, some businesses are taking advantage of widespread fears by marketing purported stem cell treatments for COVID-19. Such businesses target prospective clients with misleading claims, expose patients to potentially risky stem cell-based products, and undermine efforts to develop evidence-based treatments for COVID-19.


Assuntos
Infecções por Coronavirus/psicologia , Marketing , Pneumonia Viral/psicologia , Transplante de Células-Tronco/métodos , Betacoronavirus , Comércio , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Medo , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Transplante de Células-Tronco/economia
19.
Medicine (Baltimore) ; 99(19): e20169, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384508

RESUMO

BACKGROUND: The aim of this study is to evaluate the efficacy of neural stem cell transplantation (NSCT) for the treatment of patients with spinal cord injury (SCI). METHODS: All potential randomized controlled trials (RCTs) on NSCT in the treatment of patients with SCI will be searched from the following electronic databases: Cochrane Library, MEDILINE, EMBASE, Web of Science, Scopus, CBM, WANGFANG, and CNKI. We will search all electronic databases from their initiation to the January 31, 2020 in spite of language and publication date. Two contributors will independently select studies from all searched literatures, extract data from included trials, and evaluate study quality for all eligible RCTs using Cochrane risk of bias tool, respectively. Any confusion will be resolved by consulting contributor and a consensus will be reached. We will utilize RevMan 5.3 software to pool the data and to conduct the data analysis. RESULTS: This study will summarize the most recent RCTs to investigate the efficacy and safety of NSCT in the treatment of patients with SCI. CONCLUSION: This study will provide evidence to assess the efficacy and safety of NSCT in the treatment of patients with SCI at evidence-based medicine level. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020173792.


Assuntos
Células-Tronco Neurais , Traumatismos da Medula Espinal/terapia , Transplante de Células-Tronco/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Transplante de Células-Tronco/efeitos adversos
20.
Intern Med J ; 50(6): 667-679, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32415723

RESUMO

The COVID-19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID-19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID-19, including the use of telehealth, avoidance of non-essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy-associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID-19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID-19 and available local healthcare resources.


Assuntos
Consenso , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Controle de Infecções/métodos , Leucemia Linfocítica Crônica de Células B/fisiopatologia , Linfoma/fisiopatologia , Mieloma Múltiplo/fisiopatologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Austrália , Betacoronavirus/imunologia , Comorbidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Tratamento Farmacológico , Fidelidade a Diretrizes , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma/imunologia , Linfoma/terapia , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Nova Zelândia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Guias de Prática Clínica como Assunto , Medição de Risco , Terapia de Salvação/métodos , Transplante de Células-Tronco/métodos
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