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1.
Rinsho Ketsueki ; 62(1): 20-24, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33551420

RESUMO

Patients with refractory ascites that develops >3 months after allogenic stem cell transplantation typically have a poor prognosis. We present the case of a 61-year-old man who developed refractory massive ascites approximately 3 months after cord blood transplantation (CBT) and showed complete and spontaneous remission from ascites after 18 months. The patient complained of severe bloating and needed weekly paracentesis to manage the fluid levels. Laboratory tests indicated that the ascites was caused by liver fibrosis. After the patient underwent Keisuke-Matsusaki cell-free and concentrated ascites reinfusion therapy (KM-CART), we were able to decrease the frequency of paracentesis treatments. We planned a transjugular liver biopsy, but the patient contracted pneumocystis pneumonia before the procedure could be performed. Although the pneumonia improved, the ascites worsened again. However, weekly paracentesis spontaneously stopped the progression of ascites and eventually resolved it completely, resulting in the patient's survival.


Assuntos
Ascite , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide Aguda , Ascite/etiologia , Ascite/terapia , Humanos , Leucemia Mieloide Aguda/terapia , Cirrose Hepática/complicações , Cirrose Hepática/terapia , Masculino , Pessoa de Meia-Idade , Paracentese
2.
Ann Hematol ; 100(3): 743-752, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33427909

RESUMO

To overcome the delayed or failed engraftment after unrelated cord blood transplantation (CBT), we conducted a multicenter phase II study of intrabone single-unit CBT without antithymocyte globulin (ATG) for adult patients with hematological malignancies (UMIN-CTR, UMIN000020997). Sixty-four patients received an intrabone injection of unwashed (n = 61) or washed (n = 3) cord blood after local anesthesia. All injection-related adverse events were mild and resolved spontaneously. Sixty-two patients were evaluable for the efficacy of intrabone CBT of serological HLA-A, -B, and -DR ≥ 4/6 matched cord blood with a median number of 2.57 × 107/kg cryopreserved total nucleated cells. The probability of survival with neutrophil engraftment on day 28 was 77.4% (95% confidence interval, 67.0-85.8%), which exceeded the threshold value. The cumulative incidences of neutrophils ≥ 0.5 × 109/L on day 60 was 80.6% (68.2-88.6%), with a median time to recovery of 21 days after transplantation. The cumulative incidences of platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L on day 100 were 75.8% (62.6-84.9%) and 72.6% (59.4-82.1%), respectively, with median time to platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L of 38 and 45 days after transplantation, respectively. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease were 29.0% and 6.5%, respectively. All responded to steroid therapy, and secondary treatments were not required. The present study suggests the efficacy of intrabone single-unit CBT without ATG in terms of early engraftment and controllable acute graft-versus-host disease.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Neoplasias Hematológicas/terapia , Infusões Intraósseas/métodos , Adolescente , Adulto , Idoso , Soro Antilinfocitário , Osso e Ossos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Feminino , Sangue Fetal/fisiologia , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/epidemiologia , Humanos , Incidência , Infusões Intraósseas/efeitos adversos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
Life Sci ; 267: 118958, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33383054

RESUMO

AIMS: Spinal cord injury (SCI) is a major cause of long-term physical impairment. Currently, treatment for SCI is limited to supportive measures, which can lead to permanent disability, representing a serious social burden. The present study aimed to evaluate the inflammatory microenvironment effects of human umbilical cord mesenchymal stem cells (HUCMSCs)+ Ultrashort Wave (USW) therapy on SCI and reveal possible mechanisms. MAIN METHODS: Low-dose USW was treated one day after SCI, and HUCMSCs suspension was transferred to the lesion using a micro-syringe 7 days after SCI. The functional effects of HUCMSCs and USW, separately and combinedly, were measured, together with the infiltration of CD3+ cells, formation of A1 astrocytes and activation of NUR77/ NF-κB pathway. KEY FINDINGS: Our results showed that HUCMSCs+USW therapy improved motor function of SCI rat, together with decreased infiltration of CD3+ T cells, and decreased induction of microglia and A1 astrocytes. And also USW treatment played a very important role on decreasing the infiltration of CD3+ T cells and IBA-1+ cells. Reduced production of pro-inflammatory cytokines IL-1ß and IL-6 was also observed in rats receiving HUCMSCs+USW therapy, medicated by NUR77/NF-κB pathway. SIGNIFICANCE: These findings indicated that HUCMSCs+USW therapy could attenuate inflammatory microenvironment through NUR77/NF-κB signaling pathway, which might contribute to its better outcome.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Células-Tronco Mesenquimais/efeitos da radiação , Traumatismos da Medula Espinal/terapia , Animais , Astrócitos/metabolismo , Citocinas/metabolismo , Feminino , Inflamação/patologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Microglia/metabolismo , NF-kappa B/metabolismo , Neuroimunomodulação/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Terapia por Ondas Curtas/métodos , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Cordão Umbilical
5.
Genes (Basel) ; 12(1)2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374593

RESUMO

The placenta is a temporary organ that is discarded after birth and is one of the most promising sources of various cells and tissues for use in regenerative medicine and tissue engineering, both in experimental and clinical settings. The placenta has unique, intrinsic features because it plays many roles during gestation: it is formed by cells from two individuals (mother and fetus), contributes to the development and growth of an allogeneic fetus, and has two independent and interacting circulatory systems. Different stem and progenitor cell types can be isolated from the different perinatal tissues making them particularly interesting candidates for use in cell therapy and regenerative medicine. The primary source of perinatal stem cells is cord blood. Cord blood has been a well-known source of hematopoietic stem/progenitor cells since 1974. Biobanked cord blood has been used to treat different hematological and immunological disorders for over 30 years. Other perinatal tissues that are routinely discarded as medical waste contain non-hematopoietic cells with potential therapeutic value. Indeed, in advanced perinatal cell therapy trials, mesenchymal stromal cells are the most commonly used. Here, we review one by one the different perinatal tissues and the different perinatal stem cells isolated with their phenotypical characteristics and the preclinical uses of these cells in numerous pathologies. An overview of clinical applications of perinatal derived cells is also described with special emphasis on the clinical trials being carried out to treat COVID19 pneumonia. Furthermore, we describe the use of new technologies in the field of perinatal stem cells and the future directions and challenges of this fascinating and rapidly progressing field of perinatal cells and regenerative medicine.


Assuntos
/terapia , Placenta/citologia , Transplante de Células-Tronco/tendências , Células-Tronco/citologia , Líquido Amniótico/citologia , Ensaios Clínicos como Assunto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/tendências , Síndrome da Liberação de Citocina/terapia , Portadores de Fármacos , Membranas Extraembrionárias/citologia , Feminino , Previsões , Células-Tronco Hematopoéticas/citologia , Humanos , Pulmão/patologia , Ativação de Macrófagos , Células-Tronco Mesenquimais/citologia , Nanopartículas , Gravidez , Preservação Biológica , Medicina Regenerativa/métodos , Transplante de Células-Tronco/métodos , Células-Tronco/imunologia
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1123-1126, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798386

RESUMO

OBJECTIVE: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Juvenile myelomonocytic leukemia (JMML). METHODS: The clinical data of 5 children with JMML who were treated with unrelated UCBT from October 2011 to July 2019 were retrospectively analyzed. The age of onset for the five children (male) ranged from 0.4 to 5.0 years old, with a median age of 1.5 years old. All the patients received myeloablative conditioning regimen without ATG to whom cyclosporine A (CsA) with short-term mycophenolate mofetil (MMF) was given for GVHD prophylaxis. RESULTS: Four children acquired engraftment. One patient received secondary haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated UCBT. Grade Ⅲ to Ⅳ aGVHD occurred in 2 cases and was controlled, and none of the patients developed cGVHD. Three cases achieved long-time disease free survival,and no patient relapsed. CONCLUSION: UCBT is an effective treatment for children with JMML.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Juvenil , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Estudos Retrospectivos , Condicionamento Pré-Transplante
7.
Medicine (Baltimore) ; 99(31): e21429, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756149

RESUMO

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


Assuntos
Betacoronavirus , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Idoso , Antibacterianos/uso terapêutico , Terapia Combinada , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Feminino , Humanos , Pandemias , Pneumonia Viral/virologia , Timalfasina/uso terapêutico , Resultado do Tratamento
8.
Exp Parasitol ; 217: 107938, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768560

RESUMO

PURPOSE: Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34+ Umbilical Cord Blood Stem Cells (CD34+UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34+UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice. METHODS: Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34+UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed. RESULTS: Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34+UCBSCs and WJMSCs) & similarly the post-infection CD34+UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis. CONCLUSION: CD34+UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.


Assuntos
Antígenos CD34/sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Esquistossomose mansoni/prevenção & controle , Esquistossomose mansoni/terapia , Animais , Anti-Helmínticos/administração & dosagem , Fezes/parasitologia , Sangue Fetal/citologia , Citometria de Fluxo , Granuloma/prevenção & controle , Granuloma/terapia , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Fígado/patologia , Hepatopatias Parasitárias/prevenção & controle , Hepatopatias Parasitárias/terapia , Masculino , Células-Tronco Mesenquimais , Camundongos , Fator 3 de Transcrição de Octâmero , Contagem de Ovos de Parasitas , Praziquantel/administração & dosagem , Coloração e Rotulagem , Fator de Crescimento Transformador beta
9.
Signal Transduct Target Ther ; 5(1): 172, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855385

RESUMO

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


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Infecções por Coronavirus/terapia , Células-Tronco Hematopoéticas/virologia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Adulto , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Combinação de Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lopinavir , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Respiração Artificial , Ritonavir , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Rinsho Ketsueki ; 61(5): 468-473, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32507810

RESUMO

A 2-year and 4-month-old boy developed Langerhans cell histiocytosis (LCH) at the left parietal region of the skull. After treatment with chemotherapy, the patient achieved remission but experienced three relapses. After 3 years, he complained of headache, blurred vision, and lethargy. Brain magnetic resonance imaging revealed multiple dura-based meningeal masses. Biopsy was performed, and the patient was then diagnosed with juvenile xanthogranuloma (JXG). The analysis of both LCH/JXG tissues revealed BRAF V600E mutation. The JXG masses were not responsive to prednisolone, which was injected locally, radiotherapy (24 Gy), and chemotherapy (2-chlorodeoxy-adenosine). In addition, since the patient developed macrophage activation syndrome associated with systemic JXG progression, he received unrelated cord blood transplantation (u-CBT) at the age of 10 years and 11 months. Engraftment was performed at day 42, and significant GVHD was not observed. Four months after CBT, the patient was treated with infliximab (Remicade®) and dexamethasone palmitate (Limethasone®). The size of the intracranial JXG masses gradually decreased after u-CBT and disappeared after 4 years. Currently, the patient is doing well at the age of 25 years and is receiving androgen replacement therapy.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Histiocitose de Células de Langerhans , Xantogranuloma Juvenil , Encéfalo , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Xantogranuloma Juvenil/terapia
11.
Intern Med ; 59(12): 1519-1524, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536678

RESUMO

A 53-year-old man presented with fulminant hepatitis due to de novo hepatitis B. He had been diagnosed previously with adult T-cell leukemia (ATL) and previously resolved hepatitis B virus infection. The ATL had been treated with cord blood transplantation (CBT). He developed fulminant hepatitis 18 months after CBT, 15 months after the withdrawal of immunosuppressants, and 10 months after vitreous injections of methotrexate for ATL-related retinal infiltration. The aggressive medical protocol included entecavir, prednisolone, plasma exchange, hemodialysis, and bilirubin adsorption. We herein report successful medical treatment for fulminant de novo hepatitis B in a patient considered unsuitable for liver transplantation.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Hepatite B/complicações , Leucemia de Células T/terapia , Necrose Hepática Massiva/etiologia , Necrose Hepática Massiva/terapia , Hepatite B/terapia , Hepatite B/virologia , Humanos , Leucemia de Células T/complicações , Masculino , Necrose Hepática Massiva/diagnóstico , Pessoa de Meia-Idade
12.
Ann Rheum Dis ; 79(10): 1298-1304, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32561603

RESUMO

OBJECTIVES: To clarify the key role of circulating interferon-γ (IFN-γ) and to improve the clinical efficacy of mesenchymal stem cell (MSC) transplantation (MSCT) in patients with rheumatoid arthritis (RA). METHODS: Study of wild-type or IFN-γR-/- MSCT was first evaluated in a murine model of collagen-induced arthritis (CIA) following which a phase 1/2 randomised controlled study was conducted in 63 patients with RA who responded poorly to regular clinical treatments. Subjects were randomly assigned to an MSCT monotherapy group (n=32) or an MSCT plus recombinant human IFN-γ treatment group (n=31), with 1 year of follow-up. The primary end points consisted of efficacy as assessed as good or moderate EULAR response rates and the proportion of patients at 3 months attaining American College of Rheumatology 20 (ACR20) response rates. RESULTS: In the murine studies, wild-type MSCT significantly improved the clinical severity of CIA, while IFN-γR-/- MSCT aggravated synovitis, and joint and cartilage damage. Transitioning from the murine to the clinical study, the 3-month follow-up results showed that the efficacy and ACR20 response rates were attained in 53.3% patients with MSCT monotherapy and in 93.3% patients with MSCT combined with IFN-γ treatment (p<0.05). No new or unexpected safety issues were encountered in 1-year follow-up for either treatment group. CONCLUSIONS: The results of this study show that IFN-γ is a key factor in determining the efficacy of MSCT in the treatment of RA, and that an MSC plus IFN-γ combination therapeutic strategy can greatly improve the clinical efficacy of MSC-based therapy in RA patients.


Assuntos
Artrite Reumatoide/terapia , Terapia Combinada/métodos , Fatores Imunológicos/uso terapêutico , Interferon gama/uso terapêutico , Transplante de Células-Tronco Mesenquimais/métodos , Adulto , Animais , Artrite Experimental , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 1049-1053, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552980

RESUMO

Abstract  Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells (HSCs) for patients who were lack of HLA match related or unrelated donors. Compared with bone marrow and mobilized peripheral blood, UCB has the advantages of easy availability, safety for donors, and low requirement for HLA match between donors and recipients. However, the cell amount in UCB is relatively less, which was associated with increased graft failure, delayed hematologic recovery, immune reconstitution, and higher transplant related mortality after UCB transplantation (UCBT). Double-unit UCB is a straightforward method to augment cell amount in UCB. Compared with single-unit UCBT, double-unit CBT associated with less risk of primary disease relapse and increased incidence rate of graft-versus-host disease (GVHD), but the hematologic recovery and overall survival of recipients were no significantly difference between single and double-unit UCBT. Novel strategies for UCB expansion significantly increased the cell amount in UCB, single-unit expanded UCBT not only increased the sources of UCB, but also decreased the high cost of double-unit UCB. ATG can decrease the risk of graft failure and GVHD rate, but the role of ATG in UCBT is still controversial. Herein, the recent clinical advances on UCBT in the treatment of hematologic diseases are systematically reviewed.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Doadores não Relacionados
14.
Trials ; 21(1): 474, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32493459

RESUMO

OBJECTIVES: Objective: To undertake a pilot, feasibility RCT of umbilical cord blood derived cell therapy for treatment of adult patients infected with SARS-CoV-2 virus related moderate-to-severe pneumonia to prevent progression to severe ARDS. HYPOTHESIS: Expanded cord blood derived cell therapy will be feasible, well tolerated and show potential efficacy in the treatment of acute COVID-19 related moderate to severe pneumonia in adult patients because of their powerful anti-inflammatory and immunomodulatory properties. TRIAL DESIGN: Pilot, parallel design randomised controlled trial. PARTICIPANTS: The trial will recruit 24 hospitalised patients with confirmed SARS-CoV-2 infection and pneumonia from July to December 2020 at Monash Medical Centre in Melbourne, Australia. INTERVENTION AND COMPARATOR: Intervention: Intravenous injection of expanded umbilical cord blood cells at a dose of 5 million cells/kg (maximum dose - 500 million cells). Cell infusion will occur over 30-60 minutes through a peripheral intravenous cannula. Standard supportive care will continue as needed. Comparator: Standard supportive care. MAIN OUTCOMES: Safety and tolerability of cell administration within first 24 hours of administration; clinical improvement on a seven-category clinical improvement ordinal scale. RANDOMISATION: Randomisation will be done using computer generated allocation to intervention/ control groups in a 1:1 ratio (in blocks of 6) using sealed opaque envelopes. BLINDING (MASKING): This will be an unblinded study, given that it is the first study using expanded cord blood cells in COVID-19 patients. There will be no placebo infusion. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Twelve participants in each group. Total n=24. TRIAL STATUS: CBC-19 protocol v2, dated 23rd April 2020. Recruitment has not started yet. Estimated recruitment timeline is between 1st July - 31st December 2020. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12620000478910, registered 16th April 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
Betacoronavirus/patogenicidade , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Coronavirus/cirurgia , Pneumonia Viral/cirurgia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Progressão da Doença , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Projetos Piloto , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Vitória
17.
Hum Cell ; 33(3): 470-475, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32447573

RESUMO

Osteoarthritis is a chronic degenerative joint disease with an incidence of 81% among people aged over 65 years in China. Osteoarthritis significantly decreases the quality of life of patients, causing physical and psychological damage and posing a serious economic burden. Clinical treatments for osteoarthritis include drug and surgical treatments. Drug treatment can successfully alleviate pain but not satisfactorily reverse joint damage, while surgical intervention is typically used to treat end-stage disease. Stem cells are multi-potential progenitor cells with self-renewal and multi-lineage differentiation abilities, and can differentiate into many kinds of cells, including chondrocytes. Umbilical cord stem cells, also known as Wharton's jelly mesenchymal stem cells (WJ-MSCs), have become the first choice for cartilage regeneration engineering owing to their availability and convenience of collection. This article reviews the biological characterization of WJ-MSCs in recent years, their advantages compared with other stem cells, and their application in the treatment of osteoarthritis in animal experiments and clinical trials.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Osteoartrite/terapia , Animais , Diferenciação Celular , Células Cultivadas , Sangue Fetal/citologia , Humanos , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/fisiologia
18.
Arch Dis Child Fetal Neonatal Ed ; 105(5): 563-568, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32253200

RESUMO

Recent decades have seen the rapid progress of neonatal intensive care, and the survival rates of the most preterm infants are improving. This improvement is associated with changing patterns of morbidity and new phenotypes of bronchopulmonary dysplasia and preterm brain injury are recognised. Inflammation and immaturity are known contributors to their pathogenesis. However, a new phenomenon, the exhaustion of progenitor cells is emerging as an important factor. Current therapeutic approaches do not adequately address these new mechanisms of injury. Cell therapy, that is the use of stem and stem-like cells, with its potential to both repair and prevent injury, offers a new approach to these challenging conditions. This review will examine the rationale for cell therapy in the extremely preterm infant, the preclinical and early clinical evidence to support its use in bronchopulmonary dysplasia and preterm brain injury. Finally, it will address the challenges in translating cell therapy from the laboratory to early clinical trials.


Assuntos
Lesões Encefálicas/terapia , Displasia Broncopulmonar/terapia , Transplante de Células/métodos , Lactente Extremamente Prematuro , Doenças do Prematuro/terapia , Animais , Transplante de Células/efeitos adversos , Protocolos Clínicos , Ensaios Clínicos como Assunto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Sangue Fetal , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Terapia Intensiva Neonatal/métodos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Fatores de Tempo
19.
Zhonghua Xue Ye Xue Za Zhi ; 41(3): 204-209, 2020 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-32311889

RESUMO

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Antígenos HLA , Neoplasias Hematológicas/terapia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Receptores KIR , Estudos Retrospectivos , Adulto Jovem
20.
Rinsho Ketsueki ; 61(3): 274-279, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32224590

RESUMO

A 46-year-old female patient underwent a cord blood transplantation (conditioning regimen: fludarabine/busulfan4/melphalan80; graft-versus-host disease (GVHD) prophylaxis: tacrolimus + mycophenolate mofetil) for acute myeloid leukemia (AML) with her 1st hematological complete response to induction therapy (idarubicin 3 days+cytarabine 7 days). She lost her consciousness due to human herpesvirus 6 (HHV-6) encephalitis on day 31, and therefore, we increased the foscarnet dosage (from 120 mg/kg to 180 mg/kg). Her consciousness level improved after treatment. However, 8 hours of sudden hypothermia occurred with hyperhidrosis, hypertension, and subsequent hyperglycemia on day 34. Her condition did not improve even after administration of anticonvulsant, steroid pulse, or intravenous immunoglobulin. A total of 75 attacks were observed until she was discharged on day 471. She has not shown chronic GVHD or relapsed AML since then. However, HHV-6 caused prolonged damage to her hypothalamus as observed through magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) using 99mTc ethyl cysteinate dimer even when the virus was not detected from her cerebrospinal fluid. This damage can be responsible for the hypothermia attacks. This is the first case report of prolonged series of hypothermia attacks for over a year as a sequela of HHV-6 encephalitis after a cord blood transplantation for AML.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Hipotermia , Leucemia Mieloide Aguda , Encefalite Viral , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Infecções por Roseolovirus , Condicionamento Pré-Transplante , Transplante Homólogo
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