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1.
Lancet Haematol ; 7(2): e157-e167, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32004485

RESUMO

Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps: first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations, five members of the EBMT Transplant Complications Working Party created 38 statements on GVHD prophylaxis, drug management, and treatment of acute and chronic GVHD. Subsequently, they created the EBMT GVHD management recommendation expert panel by recruiting 20 experts with expertise in GVHD management. An email-based, two-round Delphi panel approach was used to manage the consensus. Modified National Comprehensive Cancer Network categories for evidence and consensus were applied to the approved statements. We reached 100% consensus for 29 recommendations and 95% consensus for nine recommendations. Key updates to these recommendations include a broader use of rabbit anti-T-cell globulin; lower steroid doses for the management of grade 2 acute GVHD with isolated skin or upper gastrointestinal tract manifestations; fluticasone, azithromycin, and montelukast should be used for bronchiolitis obliterans syndrome; and the addition of newer treatment options for resteroid-refractory acute and chronic GVHD. In addition, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco/efeitos adversos , Gerenciamento Clínico , Monitoramento de Medicamentos , Resistência a Medicamentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressão/métodos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos
2.
Cancer Treat Rev ; 82: 101929, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31770695

RESUMO

Autologous stem cell transplantation (ASCT) has been the mainstay of multiple myeloma (MM) treatment for approximately 30 years. Although the continuous introduction of novel agents in the armamentarium against MM has questioned its value, ASCT remains a backbone treatment for fit MM patients. However, there is no unanimous approach for several aspects including the positioning of ASCT in the therapeutic algorithm either upfront or following the first relapse, the need for single or tandem ASCT, as well as the role of ASCT as salvage therapy. Furthermore, the anti-CD38 monoclonal antibodies along with the next generation proteasome inhibitors and immunomodulatory drugs provide a platform for optimizing the induction and consolidation/maintenance regimens. In this review, we present current data pertaining to all aspects of ASCT in MM, whereas we highlight the open issues that should be addressed in the design of future clinical trials in the field.


Assuntos
Mieloma Múltiplo/terapia , Administração dos Cuidados ao Paciente , Transplante de Células-Tronco/métodos , Antineoplásicos Imunológicos/farmacologia , Humanos , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/normas , Inibidores de Proteassoma/farmacologia , Transplante Autólogo
3.
Angiol Sosud Khir ; 25(4): 7-26, 2019.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-31855197

RESUMO

Ischemic cardiomyopathy is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ischemic cardiomyopathy. Several stem cell types, including cardiac-derived stem cells, bone marrow-derived stem cells, mesenchymal stem cells, skeletal myoblasts, CD34+ and CD133+ stem cells have been used in clinical trials. Clinical effects mostly depend on transdifferentiation and paracrine factors. One important issue is that a low survival and residential rate of transferred stem cells blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ischemic cardiomyopathy mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical conditions, the particular microenvironment onto which the cells are delivered, and clinical conditions remain to be addressed. Here we provide an overview of modern methods of stem cell delivery, types of stem cells and discuss the current state of their therapeutic potential.


Assuntos
Cardiomiopatias/terapia , Isquemia Miocárdica/complicações , Transplante de Células-Tronco/métodos , Cardiomiopatias/etiologia , Humanos
4.
Medicine (Baltimore) ; 98(52): e18390, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876710

RESUMO

RATIONALE: Granulocytic sarcoma (GS), also known as chloroma, is a tumor comprising myeloblasts or monoblasts, potentially occurring as an extramedullary mass. Systemic chemotherapy should be used to induce complete remission. However, such patients with chloroma have a poorer treatment outcome than those without extramedullary myeloid sarcomas. PATIENT CONCERNS: A 30-year-old woman who initially presented with bilateral ovarian masses and splenomegaly was admitted to hospital. Also, her complete blood cell counts showed pancytopenia and blood smear revealed a few immature cells (3%). DIAGNOSES: A bone marrow biopsy demonstrated acute myelomonocytic leukemia, and the chromosomal analysis revealed a 46, XX, del18 (p11) [20] karyotype and cytogenetics and molecular markers showed all negative results. INTERVENTIONS: Since this diagnosis, she received remission-inducing chemotherapy comprising anthracycline and cytarabine, which is a standard regimen for acute myeloid leukemia (AML), and followed by allogenic hematopoietic stem cell transplantation from Human leukocyte antigen (HLA)-identical sibling donor. OUTCOMES: After transplantation, the bone marrow engrafted successfully without complications. She visited our clinic regularly with no evidence of leukemia relapse or graft-versus host disease. LESSONS: This report represents the first case of ovarian GS, wherein treatment was successful with high-dose chemotherapy, followed by allogenic hematopoietic stem cell transplantation without oophorectomy.


Assuntos
Leucemia Mieloide Aguda/terapia , Neoplasias Ovarianas/etiologia , Sarcoma Mieloide/etiologia , Transplante de Células-Tronco , Adulto , Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/uso terapêutico , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Sarcoma Mieloide/tratamento farmacológico , Sarcoma Mieloide/terapia , Transplante de Células-Tronco/métodos
6.
Medicine (Baltimore) ; 98(40): e17406, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577751

RESUMO

Serum ferritin (SF) has been identified as a potential prognostic factor for patients undergoing stem cell transplantation, but the prognostic value of SF in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients and the impact of iron chelation therapy (ICT) on MDS patients are controversial. The present meta-analysis aimed to better elucidate these relationships.Three electronic databases were searched systematically to identify reports on the prognostic role of SF in MDS and AML patients, and those investigating the impact of ICT on prognosis of MDS patients. The hazard ratios (HRs) and its 95% confidence interval (95%CI) were extracted from the identified studies using Cox proportional hazard regression model for overall survival (OS) and progression of MDS to AML.Twenty reports including 1066 AML patients and 4054 MDS patients were included in present study. The overall pooled HRs for OS of AML and MDS patients with elevated SF prior to transplantation was 1.73 (1.40-2.14), subgroup analyses stratified by the cut-off value of SF ≥1400/1000 ng/mL showed that the pooled HRs were 1.45 (0.98-2.15) and 1.65 (1.30-2.10), respectively. The pooled HRs for ICT in MDS patients was 0.30 (0.23-0.40). For ICT, the pooled HRs for the progression of MDS to AML was 0.84 (0.61-1.61).SF has a negative impact on the OS of AML and MDS patients when it is higher than 1000 ng/mL. ICT can improve the OS of MDS patients with iron overload but it is not associated with the progression of MDS to AML.


Assuntos
Terapia por Quelação/métodos , Ferritinas/sangue , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Leucemia Mieloide Aguda/complicações , Síndromes Mielodisplásicas/complicações , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/fisiopatologia , Estudos Observacionais como Assunto , Prognóstico , Modelos de Riscos Proporcionais , Projetos de Pesquisa , Transplante de Células-Tronco/métodos , Análise de Sobrevida
7.
Int J Mol Sci ; 20(17)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480448

RESUMO

Aging causes many changes in the human body, and is a high risk for various diseases. Dementia, a common age-related disease, is a clinical disorder triggered by neurodegeneration. Brain damage caused by neuronal death leads to cognitive decline, memory loss, learning inabilities and mood changes. Numerous disease conditions may cause dementia; however, the most common one is Alzheimer's disease (AD), a futile and yet untreatable illness. Adult neurogenesis carries the potential of brain self-repair by an endogenous formation of newly-born neurons in the adult brain; however it also declines with age. Strategies to improve the symptoms of aging and age-related diseases have included different means to stimulate neurogenesis, both pharmacologically and naturally. Finally, the regulatory mechanisms of stem cells neurogenesis or a functional integration of newborn neurons have been explored to provide the basis for grafted stem cell therapy. This review aims to provide an overview of AD pathology of different neural and glial cell types and summarizes current strategies of experimental stem cell treatments and their putative future use in clinical settings.


Assuntos
Doença de Alzheimer/terapia , Neurogênese , Transplante de Células-Tronco , Doença de Alzheimer/patologia , Animais , Humanos , Neuroglia/patologia , Neurônios/patologia , Transplante de Células-Tronco/métodos
8.
World Neurosurg ; 132: e246-e258, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31493613

RESUMO

OBJECTIVE: To provide an analysis of Web of Science (WoS) indexed literature related to stem cells therapy in spinal cord injury published between 1999 and 2018. METHODS: Data were obtained from the WoS Core Collection on March 30, 2019. Qualitative and quantitative analysis was conducted based on WoS. Co-citation analysis, collaboration analysis, and co-words analysis of keywords was conducted by using CiteSpace. RESULTS: A total of 4188 references were obtained. The number of publications continually increased over the investigated period. Articles were the most frequently document type. Cell Transplantation (127) was the most productive journal. Experimental Neurology (2180) was the most frequently co-cited journal. H. Okano was the most productive and influential author, with 98 publications and 4860 cited counts. The most productive country and institution were the United States and University of Toronto, respectively. Researchers and institutions from Canada, the United States, Japan, and China were the core research forces. There was a broad and close cooperation worldwide. The Lu et al.'s (2012) article (co-citation counts, 177) was the most representative and symbolic reference. Transplantation, functional recovery, marrow-derived mesenchymal stem cell treatment, and progenitor cells were the hot spots. Inflammation, glial scar, nerve regeneration, neurite outgrowth, and bone marrow stromal cell were research frontiers. CONCLUSIONS: Research on stem cells for spinal cord injury is a well-developed and promising research field. There is broad global scientific research cooperation. More cooperation among top authors, institutions, and countries is needed. Our results may be helpful for researchers in identifying further potential perspectives on collaborators, research frontiers, and hot topics.


Assuntos
Bibliometria , Traumatismos da Medula Espinal/terapia , Transplante de Células-Tronco/métodos , Humanos , Fator de Impacto de Revistas
9.
Plast Reconstr Surg ; 144(3): 397e-408e, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31461016

RESUMO

BACKGROUND: Cell-enrichment of fat grafts has produced encouraging results, but the optimal concentrations and types of added cells are unknown. The authors investigated the effects of enrichment with various concentrations of ex vivo-expanded adipose-derived stem/stromal cells and stromal vascular fraction on graft retention in a porcine model. METHODS: Adipose-derived stem/stromal cells were culture-expanded, and six fat grafts (30 ml) were prepared for each minipig (n = 13). The authors investigated grafts enriched with 2.5 × 10 to 20 × 10 adipose-derived stem cells/ml and stromal vascular fraction and nonenriched control grafts. Each pig served as its own control. Magnetic resonance imaging was performed immediately after grafting and 120 days postoperatively before the pigs were euthanized, and histologic samples were collected. RESULTS: The authors recorded an enhanced relative graft retention rate of 41 percent in a pool of all cell-enriched grafts compared to the nonenriched control (13.0 percent versus 9.2 percent; p = 0.0045). A comparison of all individual groups showed significantly higher graft retention in the 10 × 10-adipose-derived stem/stromal cells per milliliter group compared with the control group (p = 0.022). No significant differences were observed between the cell-enriched groups (p = 0.66). All fat grafts showed a significantly better resemblance to normal fat tissue in the periphery than in the center (p < 0.009), but no differences in overall graft morphology were observed between groups (p > 0.17). CONCLUSIONS: Cell-enriched fat grafting improved graft retention and was feasible in this porcine model. No significant differences in graft retention were observed among the various adipose-derived stem/stromal cell concentrations or between adipose-derived stem/stromal cell and stromal vascular fraction enrichment. Future studies using this model can help improve understanding of the role of adipose-derived stem/stromal cells in cell-enriched fat grafting.


Assuntos
Tecido Adiposo/transplante , Transplante de Células-Tronco/métodos , Células Estromais/transplante , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/citologia , Animais , Autoenxertos/citologia , Autoenxertos/diagnóstico por imagem , Contagem de Células , Estudos de Viabilidade , Sobrevivência de Enxerto , Imagem por Ressonância Magnética , Modelos Animais , Suínos , Porco Miniatura , Transplante Autólogo
10.
JAMA ; 322(8): 746-755, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454045

RESUMO

Importance: Induction chemotherapy followed by high-dose therapy with autologous stem cell transplant and subsequent antidisialoganglioside antibody immunotherapy is standard of care for patients with high-risk neuroblastoma, but survival rate among these patients remains low. Objective: To determine if tandem autologous transplant improves event-free survival (EFS) compared with single transplant. Design, Setting, and Participants: Patients were enrolled in this randomized clinical trial from November 2007 to February 2012 at 142 Children's Oncology Group centers in the United States, Canada, Switzerland, Australia, and New Zealand. A total of 652 eligible patients aged 30 years or younger with protocol-defined high-risk neuroblastoma were enrolled and 355 were randomized. The final date of follow-up was June 29, 2017, and the data analyses cut-off date was June 30, 2017. Interventions: Patients were randomized to receive tandem transplant with thiotepa/cyclophosphamide followed by dose-reduced carboplatin/etoposide/melphalan (n = 176) or single transplant with carboplatin/etoposide/melphalan (n = 179). Main Outcomes and Measures: The primary outcome was EFS from randomization to the occurrence of the first event (relapse, progression, secondary malignancy, or death from any cause). The study was designed to test the 1-sided hypothesis of superiority of tandem transplant compared with single transplant. Results: Among the 652 eligible patients enrolled, 297 did not undergo randomization because they were nonrandomly assigned (n = 27), ineligible for randomization (n = 62), had no therapy (n = 1), or because of physician/parent preference (n = 207). Among 355 patients randomized (median diagnosis age, 36.1 months; 152 [42.8%] female), 297 patients (83.7%) completed the study and 21 (5.9%) were lost to follow-up after completing protocol therapy. Three-year EFS from the time of randomization was 61.6% (95% CI, 54.3%-68.9%) in the tandem transplant group and 48.4% (95% CI, 41.0%-55.7%) in the single transplant group (1-sided log-rank P=.006). The median (range) duration of follow-up after randomization for 181 patients without an event was 5.6 (0.6-8.9) years. The most common significant toxicities following tandem vs single transplant were mucosal (11.7% vs 15.4%) and infectious (17.9% vs 18.3%). Conclusions and Relevance: Among patients aged 30 years or younger with high-risk neuroblastoma, tandem transplant resulted in a significantly better EFS than single transplant. However, because of the low randomization rate, the findings may not be representative of all patients with high-risk neuroblastoma. Trial Registration: ClinicalTrials.gov Identifier: NCT00567567.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Indução , Neuroblastoma/terapia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Quimioterapia de Consolidação , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Análise de Intenção de Tratamento , Masculino , Neuroblastoma/tratamento farmacológico , Modelos de Riscos Proporcionais , Risco , Transplante Autólogo , Adulto Jovem
11.
Expert Rev Clin Pharmacol ; 12(10): 941-946, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31465247

RESUMO

Introduction: CD123 or interleukin 3 receptor alpha is overexpressed in multiple hematologic malignancies. Tagraxofusp is an intravenously administered CD123-directed cytotoxin consisting of the fusion of interleukin-3 with a truncated diphtheria toxin payload and was recently approved by the Food and Drug Administration for the treatment of adults and children aged 2 and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN). Areas Covered: In this review, we discuss the use of tagraxofusp in BPDCN, and active clinical trials involving this agent in several hematologic malignancies are also presented. Tagraxofusp has significant efficacy in patients with BPDCN and manageable safety profile, with the most commonly reported adverse events being asymptomatic elevation of alanine and aspartate aminotransferase levels, hypoalbuminemia, peripheral edema, and thrombocytopenia. The most serious side effect is capillary leak syndrome that can be lethal in some cases but the risk may be mitigated by early recognition and intervention. Expert Opinion: Tagraxofusp has been introduced as a novel treatment of BPDCN, a rare hematologic malignancy, for which no standard therapy previously existed. Many patients treated with this agent were able to be bridged to stem cell transplantation, including older patients. In the future, combinations of tagraxofusp with other targeted agents will be explored.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Hematológicas/tratamento farmacológico , Proteínas Recombinantes de Fusão/administração & dosagem , Adulto , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Criança , Pré-Escolar , Células Dendríticas/patologia , Neoplasias Hematológicas/patologia , Humanos , Subunidade alfa de Receptor de Interleucina-3/imunologia , Terapia de Alvo Molecular , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Transplante de Células-Tronco/métodos
12.
Zool Res ; 40(5): 349-357, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31343853

RESUMO

Stem cell therapy (SCT) for Parkinson's disease (PD) has received considerable attention in recent years. Non-human primate (NHP) models of PD have played an instrumental role in the safety and efficacy of emerging PD therapies and facilitated the translation of initiatives for human patients. NHP models of PD include primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, who are responsive to dopamine replacement therapies, similar to human PD patients. Extensive research in SCT has been conducted to better treat the progressive dopaminergic neurodegeneration that underlies PD. For effective application of SCT in PD, however, a number of basic parameters still need to be tested and optimized in NHP models, including preparation and storage of cells for engraftment, methods of transplantation, choice of target sites, and timelines for recovery. In this review, we discuss the current status of NHP models of PD in stem cell research. We also analyze the advances and remaining challenges for successful clinical translation of SCT for this persistent disease.


Assuntos
Modelos Animais de Doenças , Doença de Parkinson/terapia , Primatas , Transplante de Células-Tronco/métodos , Animais , Células-Tronco/classificação
13.
Indian J Ophthalmol ; 67(8): 1265-1277, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31332106

RESUMO

Simple limbal epithelial transplantation (SLET) is an innovative limbal stem cell transplantation technique that has gained increasing popularity over the last few years. Different groups from across the world have published the clinical results of SLET in large case series with varying types and severities of limbal stem cell deficiency (LSCD). This review attempts to place all the available knowledge on SLET together in one place for the benefit of not only cornea specialists and trainees but also for residents and general ophthalmologists. It follows a balanced approach of blending evidence with experience by providing an objective analysis of published results along with helpful insights from subject experts, starting from preoperative considerations including the role of newer imaging modalities to the technical aspects of the surgery itself and the management of possible complications. Original data and novel insights on allogeneic SLET for bilateral LSCD are included in the review to address the few remaining lacunae in the existing literature on this topic. This review intends to inform, educate, and empower all aspiring and practicing SLET surgeons to optimize their clinical outcomes and to have maximal positive impact on the lives of the individuals affected by unilateral or bilateral chronic LSCD.


Assuntos
Doenças da Córnea/cirurgia , Epitélio Anterior/transplante , Limbo da Córnea/citologia , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Humanos , Transplante Autólogo , Transplante Homólogo
14.
Indian J Ophthalmol ; 67(8): 1348-1350, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31332139

RESUMO

Simple limbal epithelial transplantation (SLET) is an emerging technique for treating unilateral limbal stem cell deficiency. We report the high-resolution, anterior segment optical coherence tomography (OCT) features of the first 2 weeks of a patient undergoing SLET for an old acid injury of the right eye, repeatedly from postoperative day 1 through day 14. Three out of 11 explants with the subjacent human amniotic membrane (hAM) and the overlaid bandage contact lens were imaged. The hAM was intact and of the same thickness throughout the study period; the sub-hAM space increased from day 3 to 9 and disappeared by day 10; the explants started thinning from day 3 with the fibrin around them starting to decrease from day 2 and completely disappeared by day 4. Epithelialization occurred between day 8 and 14 and proceeded more rapidly towards the limbus than centrally. There was no change of the corneal stromal thickness or reflectivity. This case report uses high-definition, spectral-domain OCT to document the events on the ocular surface after a successful SLET surgery and opens up an avenue to study epithelialization in a convenient and noninvasive manner.


Assuntos
Ácidos , Queimaduras Químicas/diagnóstico por imagem , Doenças da Córnea/diagnóstico por imagem , Epitélio Anterior/transplante , Queimaduras Oculares/induzido quimicamente , Limbo da Córnea/citologia , Transplante de Células-Tronco/métodos , Adulto , Queimaduras Químicas/cirurgia , Doenças da Córnea/cirurgia , Queimaduras Oculares/diagnóstico por imagem , Humanos , Masculino , Período Pós-Operatório , Reepitelização , Tomografia de Coerência Óptica , Transplante Autólogo , Acuidade Visual
16.
Cell Mol Life Sci ; 76(20): 4043-4070, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31317205

RESUMO

Stem cells give rise to all cells and build the tissue structures in our body, and heterogeneity and plasticity are the hallmarks of stem cells. Epigenetic modification, which is associated with niche signals, determines stem cell differentiation and somatic cell reprogramming. Stem cells play a critical role in the development of tumors and are capable of generating 3D organoids. Understanding the properties of stem cells will improve our capacity to maintain tissue homeostasis. Dissecting epigenetic regulation could be helpful for achieving efficient cell reprograming and for developing new drugs for cancer treatment. Stem cell-derived organoids open up new avenues for modeling human diseases and for regenerative medicine. Nevertheless, in addition to the achievements in stem cell research, many challenges still need to be overcome for stem cells to have versatile application in clinics.


Assuntos
Epigênese Genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Organoides/metabolismo , Células-Tronco/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Diferenciação Celular , Transdiferenciação Celular , Reprogramação Celular , Transição Epitelial-Mesenquimal , Histonas/genética , Histonas/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Células-Tronco Neoplásicas/patologia , Organoides/patologia , Medicina Regenerativa/métodos , Nicho de Células-Tronco/genética , Transplante de Células-Tronco/métodos , Células-Tronco/classificação , Células-Tronco/citologia
17.
BMJ Case Rep ; 12(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31289159

RESUMO

Orbital involvement of multiple myeloma (MM) is uncommon, with most of those reported cases occurring at the time of initial diagnosis of MM. We present a case of an extramedullary plasmacytoma involving only the right lateral rectus of a patient who had been in disease remission. The patient presented with new-onset diplopia and an abduction deficit of the right eye, with mild proptosis. In light of her past medical history of MM, an orbital MRI was obtained. The MRI demonstrated an isolated finding of eccentric enlargement of the right lateral rectus muscle limited to the muscle belly with sparing of the tendinous insertions, leading to diagnosis of plasmacytoma. Patching of the involved eye to alleviate the symptoms of diplopia was instituted. Chemotherapy was initiated, followed by orbital radiation and stem-cell transplantation for coexisting systemic disease. The orbital symptoms of proptosis and diplopia resolved within 1 month of treatment.


Assuntos
Mieloma Múltiplo/patologia , Músculos Oculomotores/patologia , Plasmocitoma/complicações , Idoso , Quimiorradioterapia/métodos , Diplopia/diagnóstico , Diplopia/etiologia , Progressão da Doença , Exoftalmia/diagnóstico , Exoftalmia/etiologia , Evolução Fatal , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/patologia , Plasmocitoma/diagnóstico por imagem , Plasmocitoma/terapia , Transplante de Células-Tronco/métodos , Resultado do Tratamento
18.
Blood ; 134(7): 626-635, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31262783

RESUMO

High-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or primary refractory (rel/ref) chemorefractory diffuse large B-cell lymphoma. Only 50% of patients are cured with this approach. We investigated safety and efficacy of CD19-specific chimeric antigen receptor (CAR) T cells administered following HDT-ASCT. Eligibility for this study includes poor-risk rel/ref aggressive B-cell non-Hodgkin lymphoma chemosensitive to salvage therapy with: (1) positron emission tomography-positive disease or (2) bone marrow involvement. Patients underwent standard HDT-ASCT followed by 19-28z CAR T cells on days +2 and +3. Of 15 subjects treated on study, dose-limiting toxicity was observed at both dose levels (5 × 106 and 1 × 107 19-28z CAR T per kilogram). Ten of 15 subjects experienced CAR T-cell-induced neurotoxicity and/or cytokine release syndrome (CRS), which were associated with greater CAR T-cell persistence (P = .05) but not peak CAR T-cell expansion. Serum interferon-γ elevation (P < .001) and possibly interleukin-10 (P = .07) were associated with toxicity. The 2-year progression-free survival (PFS) is 30% (95% confidence interval, 20% to 70%).  Subjects given decreased naive-like (CD45RA+CCR7+) CD4+ and CD8+ CAR T cells experienced superior PFS (P = .02 and .04, respectively). There was no association between CAR T-cell peak expansion, persistence, or cytokine changes and PFS. 19-28z CAR T cells following HDT-ASCT were associated with a high incidence of reversible neurotoxicity and CRS. Following HDT-ASCT, effector CD4+ and CD8+ immunophenotypes may improve disease control. This trial was registered at www.clinicaltrials.gov as #NCT01840566.


Assuntos
Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/terapia , Receptores de Antígenos de Linfócitos T/uso terapêutico , Transplante de Células-Tronco/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Transplante Autólogo/métodos , Resultado do Tratamento
19.
Nat Med ; 25(7): 1045-1053, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31263283

RESUMO

Clinical studies of Parkinson's disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO ( NCT01898390 ), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials.


Assuntos
Neurônios Dopaminérgicos/transplante , Transplante de Tecido Fetal/métodos , Doença de Parkinson/terapia , Projetos de Pesquisa , Transplante de Células-Tronco/métodos , Ensaios Clínicos como Assunto , Humanos , Imunossupressores/uso terapêutico
20.
Cornea ; 38(10): 1280-1285, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31259860

RESUMO

PURPOSE: To investigate the surgical procedure and therapeutic efficacy of femtosecond (FS) laser-assisted keratolimbal allograft (KLAL) transplantation in the treatment of eyes with total limbal stem cell deficiency. METHODS: Ten eyes from 10 patients who underwent FS laser-assisted KLAL transplantation were enrolled. The best-corrected visual acuity (BCVA), ocular surface stability, corneal transparency, and postoperative complications were recorded. RESULTS: The keratolimbal grafts prepared using the FS laser were even in thickness and width. After the surgery, glucocorticoid and tacrolimus eye drops were administered locally to the eyes with concentration gradients, and a medium dose was prescribed for maintenance. Within the mean follow-up period of 16.8 ± 7.3 months, 9 of 10 eyes (90.0%) maintained a stable ocular surface and showed significant improvements in corneal transparency and BCVA. Persistent corneal edema only occurred in one eye because of repeated epithelial defects, and the BCVA of this eye did not improve. Confocal microscopy revealed activated dendritic cells in the Bowman membrane at the limbus, but they were always low in density with small dendritic processes. No acute immune rejection, cataracts, or elevation of intraocular pressure were detected. CONCLUSIONS: The FS laser-assisted KLAL technique can produce ring-shaped grafts with an even depth and width, resulting in a stable ocular surface and good visual prognosis. After surgery, glucocorticoids and potent immunosuppressive eye drops were administered locally with concentration gradients and effectively inhibited acute immune rejection.


Assuntos
Doenças da Córnea/cirurgia , Células Epiteliais/transplante , Terapia a Laser/métodos , Limbo da Córnea/cirurgia , Transplante de Células-Tronco/métodos , Acuidade Visual , Adulto , Aloenxertos , Doenças da Córnea/patologia , Células Epiteliais/citologia , Feminino , Seguimentos , Humanos , Limbo da Córnea/patologia , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
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