RESUMO
There is a growing interest in the potential of mesenchymal stem cells (MSCs) for implementing regenerative medicine. We assessed the effect of intravenous administration of human bone marrow-derived MSC on the life span of a single Sprague-Dawley female rat. The treatment was started when the rat was 6 months old and the cells were administered every 2 weeks afterward. The treatment did not induce any obvious changes in body growth or behavior and the rat showed the typical age changes for this strain, except that, unlike intact counterparts, the animal did not develop mammary tumors or pituitary gland hyperplasia. The more remarkable effect of the treatment was on life span, which was 44 months compared with an average of 36 months for intact laboratory rats. We conclude that despite the low N value, it is likely that the MSC treatment was responsible for the exceptionally long survival of the rat. The potential rewards of confirming the present findings warrant further studies involving higher N values.
Assuntos
Envelhecimento , Transplante de Células-Tronco Mesenquimais , Envelhecimento/patologia , Animais , Células Cultivadas , Feminino , Humanos , Hiperplasia , Longevidade , Masculino , Neoplasias Mamárias Animais/patologia , Neoplasias Mamárias Animais/prevenção & controle , Pessoa de Meia-Idade , Doenças da Hipófise/patologia , Doenças da Hipófise/prevenção & controle , Hipófise/patologia , Ratos Sprague-DawleyRESUMO
BACKGROUND: In January 2005, Rasulov et al. originally published "First experience in the use of bone marrow mesenchymal stem cells (MSCs) for the treatment of a patient with deep skin burns". Here, we present the first ever treated patient with cadaveric bone marrow mesenchymal stem cells (CMSCs) in the history of Medicine. METHODS: A young man, who severely burned 60 % of his total body surface with 30 % of full-thickness burns while working with a grass trimmer that exploded, was involved in the study. MSCs were obtained from the bone marrow of a cadaver donor in a routine procurement procedure of CUCAIBA, the Province of Buenos Aires, Argentina, Ministry of Health, Transplantation Agency, cultured, expanded, and applied on the burned surfaces using a fibrin spray after early escharotomy. RESULTS: So far, our preliminary experience and our early results have been very impressive showing an outstanding safety data as well as some impressive good results in the use of CMSCs. CONCLUSIONS: Based on all this, we think that improvements in the use of stem cells for burns might be possible in the near future and a lot of time as well as many lives could be saved by many other research teams all over the world. CMSCs will probably be a real scientific opportunity in Regenerative Medicine as well as in Transplantation.
RESUMO
The generation of singlet oxygen (SO) in the presence of specific photosensitizers (PSs) or semiconductor quantum dots (QDs) and its application in photodynamic therapy (PDT) is of great interest to develop cancer therapies with no need of surgery, chemotherapy, and/or radiotherapy. This work was focused on the identification of the main factors leading to the enhancement of SO production using Rose Bengal (RB), and Methylene Blue (MB) as PS species in organic and aqueous mediums. Subsequently, the capacity of zinc oxide (ZnO), zinc sulfide (ZnS), and ZnO/ZnS core-shell QDs as well as manganese (Mn(+2)) doped ZnO and ZnS nanoparticles (NPs) as potential PS was also investigated. Many variable parameters such as type of quencher, PSs, NPs, as well as its different concentrations, light source, excitation wavelength, reaction time, distance from light source, and nature of solvent were used. The degradation kinetics of the quenchers generated by SO species and the corresponding quantum yields were determined by monitoring the photo-oxidation of the chemical quencher and measuring its disappearance by fluorometry and spectrophotometry in the presence of NPs. Small intracellular changes of SO induced by these metal Zn (zinc) NPs and PDT could execute and accelerate deadly programs in these leukemic cells, providing in this way an innovative modality of treatment. In order to perform further more specific in vitro cytotoxic studies on B-chronic lymphocytic leukemia cells exposed to Zn NPs and PDT, we needed first to measure and ascertain those possible intracellular SO variations generated by this type of treatment; for this purpose, we have also developed and tested a novel method first described by us.
Assuntos
Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Oxigênio Singlete/metabolismo , Células Cultivadas , Humanos , Luz , Manganês/administração & dosagem , Nanopartículas/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Pontos Quânticos/administração & dosagem , Sulfetos/administração & dosagem , Compostos de Zinco/administração & dosagem , Óxido de Zinco/administração & dosagemRESUMO
One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES). The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies.
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The aim of this study was to determine if Rituximab coated Biodegradable Nanoparticles (BNPs) loaded with Chlorambucil and Hydroxychloroquine could induce apoptosis of B-Chronic Lymphocytic Leukemia (B-CLL), MEC-1 and BJAB cells in vitro and evaluate their toxic and therapeutic effects on a Human/Mouse Model of Burkitt Lymphoma at an exploratory, proof of concept scale. We found that Rituximab-Chlorambucil-Hydroxychloroquine BNPs induce a decrease in cell viability of malignant B cells in a dose-dependent manner. The mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the B-CLL cells after Annexin V/propidium iodide staining. Additional data revealed that these BNPs were non toxic for healthy animals, and had prolonged survival in this mice model of human lymphoma.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfoma de Burkitt/tratamento farmacológico , Clorambucila/uso terapêutico , Hidroxicloroquina/uso terapêutico , Nanopartículas , Animais , Anticorpos Monoclonais Murinos/farmacologia , Antineoplásicos/farmacologia , Linfócitos B/patologia , Linfoma de Burkitt/patologia , Sobrevivência Celular/efeitos dos fármacos , Clorambucila/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Hidroxicloroquina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Rituximab , Células Tumorais CultivadasRESUMO
Nonviral delivery systems are relatively easy to produce in the large scale, are safe, and elicit a negligible immune response. Nanoparticles (NPs) offer promise as nonviral vectors as biocompatible and -degradable carriers of drugs with targeting to specific sites by surface receptors of monoclonal antibodies (mAbs). We investigated the effect of four PEG-PLGA (polyethylene glycol-polylactic-co-glycolic acid) NP systems on drug-resistant B-chronic lymphocytic leukemia (B-CLL) cells in vitro, three of them encapsulating the drug, hydroxylchloroquine (HDQ), two with NP surface coatings of mAbs (NP1) CD20, (NP2) CD19, and CD20, and one (NP3) with no mAb, but tagged with the fluorescent marker, fluorescein isothiocyanate. The fourth NP system (NP4) was coated with anti-CD19/FITC and anti-CD20/Alexa-Fluor((R)) antibodies, but did not contain the active drug, HCQ. Our data indicate that PEG-PLGA nanoparticles with surface mAbs are suitable for selective drug delivery to B-CLL cells and produce a strong apoptotic effect when loaded with the lysosomotropic agent, HDQ.
Assuntos
Hidroxicloroquina/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Nanopartículas/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Microscopia Confocal , Espectrometria de FluorescênciaRESUMO
BACKGROUND: B-cell chronic lymphocytic leukemia (B-CLL) still remains as an uncurable disease. Even the newest antineoplastic agents have demonstrated limitations in their efficacy. For this reason, further research of new compounds must be done. New pharmacological properties can be obtained from a great diversity botanical species. Among these products, Magnolia Grandiflora receives our attention since it mainly contains Honokiol which had demonstrated effect against B-CLL cells activating different cell death pathways. AIM: To test the ability of Magnolia Grandiflora extracts to induce apoptosis of B-CLL cells in vitro. MATERIALS AND METHODS: Herb's extraction: Twenty grams of powdered material were submitted to three consecutives decoctions with 500 ml of distilled water (96 °C), filtered and followed by ultrafiltration with cellulose membrane, lyophilized and reconstituted in AIM-V medium at a final concentration of 10 mg/ml solution. B-CLL chlorambucil-resistant cells were separated and cultivated in the presence of Magnolia's extract. Samples of cells were taken from the cultures at 24, 48 and 72 h for apoptosis analysis by flow cytometry measuring positive annexin V (0.1 µg/ml) cells. STATISTICS: Apoptosis values were represented by the mean plus or minus SD (± SD) for five independent experiments. Statistical significance was determined by Student's t-test. A P value of 0.05 or less was considered as significant. RESULTS AND CONCLUSION: This article discusses the apoptosis properties of Magnolia on B-CLL cells. The evidence suggests a potentially effective repertoire for B-CLL treatment. This herb extract might have promising therapy strategies in treating B-CLL or other hematological disease resistant to alkylating agents in clinical practice.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Clorambucila/farmacologia , Leucemia Linfocítica Crônica de Células B/patologia , Magnolia/química , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , HumanosAssuntos
Humanos , Adulto , Pessoa de Meia-Idade , Anticoagulantes , Veias Mesentéricas , Trombose , Trombose Venosa , HematologiaRESUMO
Evidences of the relationship between immunological disturbances and diseases are more conclusive every day. IDDM is a good example of an autoimmunne process associated with a severe clinical picture.
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Humanos , Diabetes Mellitus Tipo 1RESUMO
Evidences of the relationship between immunological disturbances and diseases are more conclusive every day. IDDM is a good example of an autoimmunne process associated with a severe clinical picture. (AU)
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Humanos , Diabetes Mellitus Tipo 1/imunologiaRESUMO
El tema "niño de la calle" es netamente urbano y tiene correspondencia con la problemática de la migración y el desarrollo de los pueblos jóvenes, así como el auge del sector informal de la economía urbana. Esta búsqueda bibliográfica abarca desde 1965 hasta 1985 de producción académica. En este documento se presenta la información recuperada, tematizadas en tres grandes categorías: Niño y adolescente; Familia; Comunidad, todas precedidas de un breve análisis y comentario