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1.
Cell Physiol Biochem ; 53(5): 887-909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749350

RESUMO

Over the past years, the benefits of stem cell therapy approach for treatment of the cardiovascular diseases have been shown through the rebuilding of new cardiomyocytes and blood vessels. while a successful regeneration of the myocardium has been proven on the animal models of acute myocardial injuries resulted from the stem cells transplantation, no significant long-term regenerative with autologous stem cell therapy in patients with acute myocardial infarction have been reported based on recent meta-analyses. It seems that the inflammatory microenvironment of acute myocardial infarction has an inhibitory effect on the stem cells potential for regenerating the injured myocardium. Secretion of critical cytokines with pro-inflammatory properties including tumor necrosis factor-α, interleukin-1ß, and interleukin-6 as well as induction of hypoxic condition and finally formation of cytotoxic elements cause the cellular death and hinder the stem cells proliferation and differentiation. Based on the evidence, application of some approaches like co-delivery of mesenchymal stem cells with the other useful cells, using the stem cells derived productions, administration of preconditioned and modified cells, and also using the anti-inflammatory agents besides the cell therapy are hypothesized as the primary developed safe and practical approaches for decreasing destructive effects of the inflammation on the implanted stem/progenitor cells. In this review, we critically discuss the quiddity of the inflammatory microenvironment and its promoted mechanisms as the main elements to hinder the efficacy of stem cell therapy in the cases of acute myocardial infarction. Also, we finally propose some applied solutions to the problem of cardiac regeneration with stem cells therapy.


Assuntos
Infarto do Miocárdio/terapia , Transplante de Células-Tronco , Terapia Baseada em Transplante de Células e Tecidos , Microambiente Celular , Ensaios Clínicos como Assunto , Citocinas/metabolismo , Coração/fisiologia , Humanos , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Regeneração/fisiologia , Células-Tronco/citologia , Células-Tronco/metabolismo
2.
Rinsho Ketsueki ; 60(10): 1455-1461, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31695007

RESUMO

A 64-year-old woman was diagnosed with diffuse large B-cell lymphoma (DLBCL) in 2013. After eight courses of R-CHOP therapy followed by local irradiation of the remaining retroperitoneal soft tissue shadow, complete response was confirmed on 18F-2-fluoro-2-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). Early in 2016, patient's serum LDH and soluble IL-2 receptor levels elevated. With suspected recurrence of DLBCL, FDG-PET/CT was performed that showed no lymphadenopathy or abnormal FDG uptake. By the end of July 2016, the patient developed fever and night sweating. Intravascular large B-cell lymphoma (IVLBCL) was suspected, and the patient underwent random skin biopsies, which revealed large atypical cells infiltrating peripheral and intravascular regions of the subcutaneous adipose tissue. Cell morphology, immunostaining, and PCR analysis of the immunoglobulin heavy chain gene suggested the recurrence of DLBCL. Despite salvage chemotherapy and autologous peripheral stem cell transplantation with high-dose chemotherapy, approximately 15 months later, DLBCL recurred and involved the lungs. The patient again received chemotherapy and achieved a second remission. Because DLBCL may recur like intravascular lymphoma, the same tests used for IVLBCL diagnosis are required in cases of suspected recurrence of DLBCL based on clinical and laboratory findings.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico , Neoplasias Vasculares/diagnóstico , Idoso , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Feminino , Fluordesoxiglucose F18 , Humanos , Linfoma Difuso de Grandes Células B/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons , Prednisona , Recidiva , Indução de Remissão , Terapia de Salvação , Transplante de Células-Tronco , Neoplasias Vasculares/terapia , Vincristina
3.
Zhonghua Shao Shang Za Zhi ; 35(9): 645-654, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594182

RESUMO

Objective: To investigate whether adipose-derived stem cells (ASCs) from allogeneic diabetic rats can promote wound healing in diabetic rats or not and the mechanism. Methods: (1) Fifty-six male Wistar rats aged 12-16 weeks were divided into diabetic group and healthy group according to the random number table (the same grouping method below), with 28 rats in each group. Rats in healthy group were not treated with any treatment. Rats in diabetic group were injected with 10 g/L streptozotocin 60 mg/kg intraperitoneally in one time to establish the diabetic model. Four rats in diabetic group and 4 rats in healthy group were selected according to the random number table, and the adipose tissue in the inguinal region was taken to culture and purify ASCs, so as to obtain healthy rat-derived ASCs (hereinafter referred to as nASCs) and diabetic rat-derived ASCs (hereinafter referred to as dASCs). The third passage of nASCs (n=3) and dASCs (n=3) were taken, and the positive expression rates of cell surface differentiation antigens CD105, CD31, CD34, and CD44 were detected with flow cytometer for defining ASCs purity. (2) The rest 24 rats in healthy group and 24 rats in diabetic group were used to make three round full-thickness skin defect wounds with a diameter of 12 mm on the back of each rat. Immediately after injury, phosphate buffer saline (PBS), nASCs of 2×10(7)/mL, and dASCs of 2×10(7)/mL each in the volume of 0.5 mL were subcutaneously injected into three wounds and their margins of each rat, respectively. On post injury day (PID) 1, 3, 7, and 12, 6 rats in each group were selected according to the random number table to calculate the wound area, and the wound tissue was stained with hematoxylin-eosin to observe the histological morphology of the wound. (3) Human ASCs (hASCs) were subcultured, and the 4th to 7th passage of cells were used for the subsequent experiments. The hASCs were divided into 7 groups, with 12 samples in each group. Cells in blank control group were cultured with mesenchymal stem cell culture medium, and cells in simple advanced glycation end products (AGEs) group, simple protein group, simple high glucose group, simple high osmotic pressure group, AGEs-high glucose combination group, and protein-high osmotic pressure combination group were cultured with mesenchymal stem cell culture medium containing a final mass concentration of 100 mg/L AGEs, 100 mg/L bovine serum albumin (BSA), 28 mmol/L D-glucose, 28 mmol/L mannitol, 100 mg/L AGEs+ 28 mmol/L D-glucose, 100 mg/L BSA+ 28 mmol/L mannitol, respectively. Cell proliferation was detected by cell counting kit 8 at post culture hour (PCH) 2 and on post culture day (PCD) 2, 4 and 6. (4) The hASCs were divided into blank control group, simple AGE group, simple high glucose group, and AGE-high glucose combination group, with 12 samples in each group, which were treated the same as corresponding groups in experiment (3). On PCD 0, 2, 4, and 6, the positive expression rates of cell surface differentiation antigens CD105, CD44, and CD45 were detected by flow cytometer to estimate their homeostasis. (5) The hASCs were divided into AGE-high glucose combination group and protein-high osmotic pressure combination group, with 9 samples in each group, which were treated the same as corresponding groups in experiment (3). On PCD 2, 4, and 6, the expression of intracellular protein was detected by cyanine 3-streptavidin double-antibody sandwich technique. Data were processed with analysis of variance for factorial design, least significant difference test, and Bonferroni correction. Results: (1) The positive expression rates of CD44 in nASCs and dASCs were both higher than 96%, the positive expression rates of CD31 and CD34 were low, and the positive expression rates of CD105 were about 40%, which basically met the purity requirements. (2) The areas of wounds treated by three methods in rats of healthy group and diabetic group were similar on PID 1 (P>0.05). In healthy group, compared with (0.682 1±0.078 9), (0.314 3±0.113 7), and (0.064 3±0.002 1) cm(2) of the PBS-treated wounds in rats, the area of nASCs-treated wounds in rats decreased significantly on PID 3, 7, and 12 [(0.464 1±0.092 6), (0.223 9±0.072 7), and (0.034 3±0.012 5) cm(2), P<0.05], the area of dASCs-treated wounds in rats decreased significantly on PID 3 and 12 [(0.514 1±0.124 1) and (0.043 7±0.032 8) cm(2), P<0.05] but was not obviously changed on PID 7 [(0.274 2±0.062 5) cm(2), P>0.05]. Compared with those of the dASCs-treated wounds of rats within the same group, the area of the nASCs-treated wounds of rats in healthy group decreased significantly on PID 3 and 7 (P<0.05) but was not obviously changed on PID 12 (P>0.05). In diabetic group, compared with (0.853 5±0.204 8), (0.670 5±0.164 8), and (0.131 4±0.074 4) cm(2) of the PBS-treated wounds in rats, the area of nASCs-treated wounds in rats decreased significantly on PID 3, 7, and 12 [(0.633 4±0.132 5), (0.331 8±0.023 5), and (0.074 2±0.003 8) cm(2), P<0.05], the area of dASCs-treated wounds in rats decreased significantly on PID 3 [(0.773 6±0.182 2) cm(2), P<0.05] but was not obviously changed on PID 7 and 12 [(0.510 6±0.192 2) and (0.114 4±0.003 1) cm(2), P>0.05]. Compared with the dASCs-treated wounds of rats within the same group, the area of the nASCs-treated wounds of rats in diabetic group was not obviously changed on PID 3 and 7 (P>0.05) but decreased significantly on PID 12 (P<0.05). There was no obvious difference in histological morphology of the wounds treated with three methods in rats of each group on PID 1. On PID 3, a small amount of microvessels were formed in the wounds treated with nASCs and dASCs of rats in both groups, but microvessel formation was almost undetected in the PBS-treated wounds. On PID 7, more small blood vessels and fibroblasts (Fbs) were observed in the wounds treated with nASCs and dASCs of rats in both groups, but the small blood vessels and Fbs were slightly less in the PBS-treated wounds. On PID 12, the wounds treated with nASCs and dASCs of rats in the two groups were covered by epithelial tissue, the granulation tissue in the PBS-treated wounds of rats in healthy group was not obvious, and the PBS-treated wounds of rats in diabetic group were not completely epithelialized. (3) Compared with those of blank control group, the cell number of hASCs in simple AGEs group decreased significantly on PCD 2, 4, and 6 (P<0.05), which increased significantly on PCD 2 and 4 in simple high glucose group (P<0.05), and that in AGEs-high glucose combination group decreased significantly on PCD 4 and 6 (P<0.05). (4) Compared with that on PCD 4 within the same group, the positive expression rate of CD105 in hASCs decreased significantly in blank control group, simple AGEs group, and AGEs-high glucose combination group on PCD 6 (P<0.05). The positive expression rate of CD44 was higher than 95%, and that of CD45 was less than 2% in hASCs of each group at each time point. (5) Detection values of 7 proteins were located in the confidence interval. The expression levels of basic fibroblast growth factor and tissue inhibitor of metalloproteinase-1 in hASCs of AGEs-high glucose combination group and protein-high osmotic pressure combination group showed increasing trend with the prolongation of culture time. The expression level of human monocyte chemoattractant protein 1 (MCP-1) in hASCs of AGEs-high glucose combination group showed increasing trend with the prolongation of culture time, while the expression level of growth-regulated oncogene (GRO) on PCD 6 was significantly higher than that on PCD 4 within the same group (P<0.05); the expression levels of MCP-1 and GRO in hASCs of protein-high osmotic pressure combination group showed decreasing trend with the prolongation of culture time. The expression level of follistatin in hASCs of protein-high osmotic pressure combination group decreased obviously on PCD 4, while that in hASCs of AGEs-high glucose combination group was significantly lower on PCD 6 than that on PCD 4 (P<0.05). The expression level of vascular endothelial growth factor (VEGF) in hASCs of protein-high osmotic pressure combination group decreased gradually with the prolongation of culture time, while that in hASCs of AGEs-high glucose combination group on PCD 4 decreased significantly as compared with that on PCD 2 (P<0.05). The expression level of urokinase-type plasminogen activator receptor in hASCs of protein-high osmotic pressure combination group on PCD 6 was significantly higher than that on PCD 4 within the same group (P<0.05) and that of AGEs-high glucose combination group on PCD 6 (P<0.05). Conclusions: Both nASCs and dASCs can promote wound healing in rats with simple defect injury, but dASCs have no significant effect on wound healing in rats with diabetes mellitus, which may be related to the inhibition of ASCs proliferation and the influence of high glucose and AGEs intervention on their homeostasis and secretory function.


Assuntos
Diabetes Mellitus Experimental/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Cicatrização , Tecido Adiposo/citologia , Animais , Células Cultivadas , Diabetes Mellitus Experimental/complicações , Humanos , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
4.
Adv Exp Med Biol ; 1186: 55-97, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31654386

RESUMO

In developed countries, blindness and visual impairment are caused mainly by diseases affecting the retina. These retinal degenerative diseases, including age-related macular dystrophy (AMD) and inherited retinal diseases such as retinitis pigmentosa (RP), are the predominant causes of human blindness worldwide and are responsible for more than 1.5 million cases in France and more than 30 million cases worldwide. Global prevalence and disease burden projections for next 20 years are alarming (Wong et al., Lancet Glob Health 2(2):e106-e116, 2014) and strongly argue toward designing innovative eye-care strategies. At present, despite the scientific advances achieved in the last years, there is no cure for such diseases, making retinal degenerative diseases an unmet medical need.The majority of the inherited retinal disease (IRD) genes codes for proteins acting directly in photoreceptors. Yet, a few of them are expressed in the retinal pigment epithelium (RPE), the supporting tissue necessary for proper functioning of the photoreceptors. Among retinal degenerative diseases, impairment of some RPE genes engenders a spectrum of conditions ranging from stationary visual defects to very severe forms of retinal dystrophies in which the RPE dysfunction leads to photoreceptors cell death and consecutive irreversible vision loss. The accessibility of the eye and the immune privilege of the retina, together with the availability of noninvasive imaging technologies, make such inherited retinal dystrophies a particularly attractive disease model for innovative cell therapy approaches to replace, regenerate, and/or repair the injured RPE tissue. Proof-of-concept studies in animal models have demonstrated the safety and efficacy of the engraftment of therapeutic cells either to support RPE cell functions or to provide a trophic support to photoreceptors. These different approaches are now in the pipeline of drug development with objective to provide first cell-based treatments by 2020.This chapter will focus on the different cell-based strategies developed in the past and current approaches to prevent photoreceptor death in RPE-associated degenerative eye diseases.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Degeneração Retiniana , Epitélio Pigmentado da Retina , Animais , França , Humanos , Degeneração Retiniana/terapia , Epitélio Pigmentado da Retina/patologia , Transplante de Células-Tronco
5.
Adv Exp Med Biol ; 1186: 99-119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31654387

RESUMO

There is an increasing effort toward generating replacement cells for neuronal application due to the nonregenerative nature of these tissues. While much progress has been made toward developing methodologies to generate these cells, there have been limited improvements in functional restoration. Some of these are linked to the degenerative and often nonreceptive microenvironment that the new cells need to integrate into. In this chapter, we will focus on the status and role of the immune microenvironment of the retina during homeostasis and disease states. We will review changes in both innate and adaptive immunity as well as the role of immune rejection in stem cell replacement therapies. The chapter will end with a discussion of immune-modulatory strategies that have helped to ameliorate these effects and could potentially improve functional outcome for cell replacement therapies for the eye.


Assuntos
Retina , Transplante de Células-Tronco , Imunidade Adaptativa , Microambiente Celular/imunologia , Humanos , Imunidade Inata , Imunomodulação , Neurônios/fisiologia , Retina/imunologia , Degeneração Retiniana/imunologia , Degeneração Retiniana/patologia , Degeneração Retiniana/terapia
6.
Cancer Immunol Immunother ; 68(11): 1891-1899, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31628525

RESUMO

Acute myeloid leukemia (AML) is the most common acute leukemia in adults and overall survival remains poor. Chemotherapy is the standard of care for intensive induction therapy. Patients who achieve a complete remission require post-remission therapies to prevent relapse. There is no standard of care for patients with minimal residual disease (MRD), and stem cell transplantation is a salvage therapy. Considering the AML genetic heterogeneity and the leukemia immune-suppressive properties, novel cellular immune therapies to effectively harness immunological responses to prevent relapse are needed. We developed a novel modality of immune therapy consisting of monocytes reprogrammed with lentiviral vectors expressing GM-CSF, IFN-α and antigens. Preclinical studies in humanized mice showed that the reprogrammed monocytes self-differentiated into highly viable induced dendritic cells (iDCs) in vivo which migrated effectively to lymph nodes, producing remarkable effects in the de novo regeneration of T and B cell responses. For the first-in-man clinical trial, the patient's monocytes will be transduced with an integrase-defective tricistronic lentiviral vector expressing GM-CSF, IFN-α and a truncated WT1 antigen. For transplanted patients, pre-clinical development of iDCs co-expressing cytomegalovirus antigens is ongoing. To simplify the product chain for a de-centralized supply model, we are currently exploring a closed automated system for a short two-day manufacturing of iDCs. A phase I clinical trial study is in preparation for immune therapy of AML patients with MRD. The proposed cell therapy can fill an important gap in the current and foreseeable future immunotherapies of AML.


Assuntos
Antígenos de Neoplasias/metabolismo , Vetores Genéticos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Imunoterapia , Interferon-alfa/metabolismo , Leucemia Mieloide Aguda/terapia , Monócitos/imunologia , Células Dendríticas/imunologia , Humanos , Lentivirus/genética , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/metabolismo , Medicina de Precisão , Transplante de Células-Tronco
7.
Zhonghua Xue Ye Xue Za Zhi ; 40(9): 732-737, 2019 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-31648473

RESUMO

Objective: To compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) . Methods: Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively. Results: ①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3(rd) month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) . Conclusion: HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Bussulfano , Ciclofosfamida , Combinação de Medicamentos , Etoposídeo , Humanos , Melfalan , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante de Células-Tronco , Condicionamento Pré-Transplante , Transplante Autólogo
8.
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
9.
Rinsho Ketsueki ; 60(8): 960-967, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484896

RESUMO

Myelodysplastic syndromes (MDS) constitute a group of heterogeneous disorders of hematopoietic stem cells, characterized by defective hematopoiesis and multilineage dysplasia. While low-risk subtypes normally exhibit a relatively chronic clinical course, high-risk subtypes harbor unfavorable prognosis in which hematopoietic stem cell transplantation (HCT) is the only curative therapy. Nevertheless, transplantation-related mortality is relatively high and should be weighed against the potential benefits of HCT. Hence, it is vital to precisely stratify the prognostic risks before HCT for predicting and enhancing their prognosis. Recently, our understanding of the genetic basis of MDS has substantially advanced, through which a full spectrum of major mutational targets was delineated. Moreover, its effects in the setting of HCT have also been assessed besides the conventional predictive factors. While clinical factors account for as much as 70% of the total hazard of MDS cases treated with HCT, the remaining 30% is explicated by genetic factors. The integration of genetic test and conventional clinical factors could be useful for precise stratification of the prognostic risks and, therefore, treatment decision in MDS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Mutação , Prognóstico , Transplante de Células-Tronco
13.
Angiol Sosud Khir ; 25(3): 39-52, 2019.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-31503246

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 , Infarto do Miocárdio , Isquemia Miocárdica , Transplante de Células-Tronco , Cardiomiopatias/terapia , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Isquemia Miocárdica/terapia
14.
Indian J Med Res ; 149(6): 693-694, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31496521
15.
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
16.
Orthop Clin North Am ; 50(4): 415-423, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31466658

RESUMO

There is a growing interest in cell therapy for knee osteoarthritis. This study systematically reviews the current status of cell-based therapies. The authors review treatment modalities, clinical outcomes, and the economics of cell therapy. Inclusion criteria were articles containing cellular therapy, platelet-rich plasma, and knee osteoarthritis in the title. Letters, editorial material, abstracts not published, and manuscripts with incomplete data were excluded. Forty-two articles met these inclusion criteria and were critically reviewed. Cell-based therapy holds promise as a means of restoring deficient local cartilage cell populations. There is no evidence-based information for the use of cell-based therapies in knee osteoarthritis.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/economia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Osteoartrite do Joelho/terapia , Terapia Baseada em Transplante de Células e Tecidos/normas , Análise Custo-Benefício , Política de Saúde , Humanos , Plasma Rico em Plaquetas/citologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Células-Tronco , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1330-1333, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418402

RESUMO

Abstract  Myelodysplastic syndromes (MDS) represent a clonal hematopoietic stem cell disorder characterized by morphologic features of dyspoiesis, high risk of transformation from MDS into AML. Allogeneic hematopoietic stem-cell transplantation is the only curative therapy for MDS, but the failure rate of transplantation is still high, which attribute to relapsed disease and transplant-related complications. Recently, the spectrum of gene abnormalities in MDS has been revealed by next generation genomic sequencing techniques. It was found that more than 80% MDS patients have at least one gene mutation. Mutated genes in MDS are powerfully associated with clinical phenotype and prognosis. In this review , the recent advancements regarding recurrent gene mutations in MDS are briefly summarized, and the  prognostic values of gene mutations are discussed in MDS or after allogeneic hematopoietic stem-cell transplantation,so as to set up a predicting model and to guide the treatment.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Mutação , Prognóstico , Transplante de Células-Tronco
19.
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
20.
Ann Hematol ; 98(10): 2399-2405, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31375860

RESUMO

Rituximab was recently described also as first-line therapy of chronic graft-versus-host disease (cGvHD). We retrospectively analyzed the efficacy and safety of all patients receiving rituximab for treatment of cGvHD between 2005 and 2016 at the Regensburg University transplant center with a median follow-up after rituximab therapy of 2.8 years. Responses of 29 allogeneic stem cell-transplanted patients (median age 49) with previous failure of response to steroids including one patient after donor lymphocyte infusion were assessed. Three months after rituximab application, the overall response rate was 31% (7% complete (n = 2) and 24% partial remission (n = 7)). At 12 months, overall survival was 72% (n = 21) and failure-free survival was 24% (n = 7). We further analyzed associations of rituximab response with clinical characteristics showing a higher response rate in steroid-dependent cGvHD patients (89% of 9 responding compared to steroid refractory patients (11% responding)). However, this difference was not statistically significant. Seven patients (24%) (including four lethal infectious complications) developed serious infections requiring hospitalization within 1-9 months after rituximab therapy exclusively in patients failing to respond to rituximab. In conclusion, rituximab appears to be an effective treatment of cGvHD especially in steroid dependent patients, but identification of biomarker predicting response will be crucial to avoid long-term infectious morbidity and mortality in non-responders.


Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Rituximab/administração & dosagem , Adulto , Idoso , Aloenxertos , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco , Taxa de Sobrevida
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