RESUMEN
Treatment using the cell sheet technology has been applied to various organs, including the cornea, heart, esophagus, periodontium, cartilage, middle ear, and lungs. It has been shown that the therapeutic efficacy of cell sheet transplantation involves 2 aspects, supplementation of cells and provision of cytokines to the affected organ. In addition, cell sheet transplantation also promotes repair of damage through the paracrine effects of cytokines derived from the transplanted cells. It is known that in cases of cell transplantation by injection, the transplanted cells are less likely to differentiate into renal tissue to supply cells, but repair is promoted by the actions of the transplanted cell-derived renotropic factors. Renal function requires functional conjugation of various tissues, including blood vessels, glomeruli, renal tubules, and collecting ducts. It is difficult to supply the necessary cells directly to the affected site of the renal tissue composed of complex structures. On the contrary, the 2-dimensional cell sheet can produce proteins such as erythropoietin, and is thus suitable for transplantation into the living body. It would be desirable to develop cell sheet therapy for the suppression of kidney damage in the future, taking advantage of the beneficial characteristics of cell sheets.
Asunto(s)
Células Cultivadas/trasplante , Insuficiencia Renal/terapia , Trasplante de Células Madre/métodos , Trasplante de Células/métodos , Células Cultivadas/metabolismo , Colecalciferol/metabolismo , Técnicas de Cultivo/métodos , Citocinas/metabolismo , Eritropoyetina/biosíntesis , Humanos , Riñón/fisiología , Enfermedades Renales/terapia , Regeneración , Ingeniería de Tejidos/métodosRESUMEN
Umbilical cord blood (CB) is a rich source of hematopoietic stem cells (HSCs) with important applications in allogeneic stem cell transplantation. However, the low numbers of hematopoietic stem and progenitor cells (HSPCs) in banked units remain a major limitation. Protocols developed for HSPC expansion ex vivo or to improve HSPC homing to the marrow represent solutions to overcome this shortcoming. In recent decades, wide arrays of functionally divergent approaches were developed for the amplification of HSPCs. These include optimization of cytokine cocktails, coculture systems, small molecules, and delivery systems for HSPC-expansion genes. Herein, we review past and current strategies, focusing on studies that characterize the contribution of expanded CB HSPC to short- and long-term engraftment in transplantation models or in clinical trials. Also discussed are homing effectors used to promote engraftment. In summary, these studies underscore that early-acting cytokines alone can expand HSPC with short-term engraftment activity, but that robust expansion of HSPCs with long-term engraftment necessitates the synergistic action of multiple HSC-expansion agonists. In support of this, early clinical trials based on cytokine-driven HSPC-expansion protocols delivered disappointing results, whereas recent trials based on the synergistic action of cytokines and HSPC-expansion agonists reported significant improvements in engraftment and therapeutic outcomes. Conversely, molecules that enhance homing of HSPC may represent a complementary approach to improve and perhaps accelerate engraftment. Optimization of the next generation of HSPC-expansion and priming strategies should support a paradigm shift in CB transplantation in which smaller, better matched units may preferentially be used.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Células Madre Hematopoyéticas/citología , Animales , División Celular/efectos de los fármacos , Movimiento Celular , Células Cultivadas/trasplante , Ensayos Clínicos como Asunto , Técnicas de Cocultivo , Citocinas/farmacología , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Sangre Fetal/citología , Estudios de Asociación Genética , Supervivencia de Injerto/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Xenoinjertos , Humanos , Inmunofenotipificación/métodos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Transducción de Señal/genética , Bibliotecas de Moléculas Pequeñas , Células del Estroma/citología , Investigación Biomédica Traslacional , Resultado del TratamientoRESUMEN
OBJECTIVE: The signaling by thrombopoietin (TPO) via its receptor, c-MPL, plays a crucial role in the maintenance of hematopoietic stem cells (HSCs). Small-molecule c-MPL agonists have recently been shown to be beneficial in the treatment of thrombocytopenia. However, their effects on HSCs have not yet been explored. In this study, we evaluated the effects of NR-101, a novel small-molecule c-MPL agonist, on the ex vivo expansion of human cord blood (hCB) HSCs. MATERIALS AND METHODS: hCB CD34(+) or CD34(+)CD38(-) hematopoietic stem and progenitor cells were cultured for 7 days in the presence of thrombopoietin (TPO) or NR-101, and then subjected to flow cytometric analyses, colony-forming cell assays, and severe combined immunodeficiency-repopulating cell assays. RESULTS: During a 7-day culture of CD34(+) or CD34(+)CD38(-) hematopoietic stem and progenitor cells, NR-101 efficiently increased their numbers, with a greater than twofold increase compared to TPO, although its effect on megakaryocytopoiesis was comparable to that of TPO. Correspondingly, severe combined immunodeficiency-repopulating cells were increased 2.9-fold during a 7-day culture with NR-101 compared to freshly isolated CD34(+) cells, and 2.3-fold compared to that with TPO. Of note, NR-101 persistently activated signal transducer and activator of transcription (STAT) 5 but not signal transducer and activator of transcription 3. Furthermore, NR-101 induced a long-term accumulation of hypoxia-inducible factor-1alpha protein and enhanced activation of its downstream target genes. CONCLUSION: This is the first time that a small-molecule c-MPL agonist has been demonstrated to promote net expansion of HSCs. NR-101 is more efficient in ex vivo expansion of HSCs than TPO. NR-101 could be a useful tool for the therapeutic manipulation of human HSCs.
Asunto(s)
Células Madre Hematopoyéticas/efectos de los fármacos , Receptores de Trombopoyetina/agonistas , Trombopoyesis/efectos de los fármacos , Animales , Hipoxia de la Célula/efectos de los fármacos , Hipoxia de la Célula/genética , Línea Celular Tumoral/citología , Línea Celular Tumoral/efectos de los fármacos , Células Cultivadas/citología , Células Cultivadas/efectos de los fármacos , Células Cultivadas/trasplante , Trasplante de Células Madre de Sangre del Cordón Umbilical , Subunidad beta Común de los Receptores de Citocinas/genética , Subunidad beta Común de los Receptores de Citocinas/fisiología , ADN Complementario/genética , Evaluación Preclínica de Medicamentos , Sangre Fetal/citología , Regulación de la Expresión Génica/efectos de los fármacos , Células Madre Hematopoyéticas/citología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Receptor de Interleucina-3/genética , Subunidad alfa del Receptor de Interleucina-3/fisiología , Leucemia Mieloide/patología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Quimera por Radiación , Receptores de Eritropoyetina/genética , Receptores de Eritropoyetina/fisiología , Receptores de Trombopoyetina/genética , Receptores de Trombopoyetina/fisiología , Proteínas Recombinantes de Fusión/fisiología , Transducción de Señal/efectos de los fármacos , Trombopoyetina/farmacologíaRESUMEN
BACKGROUND: Mesenchymal stem cells (MSCs)-based regenerative therapy is currently regarded as an alternative approach to salvage the acute myocardial infarcted hearts. However, the efficiency of MSCs transplantation is limited by lower survival rate of engrafted MSCs. In previous study, we found that 1.0 microg/ml Lipopolysaccharide (LPS) could protect MSCs against apoptosis induced by oxidative stress and meanwhile enhance the proliferation of MSCs. Therefore, in the present study, we firstly preconditioned MSCs with 1.0 microg/ml LPS, then transplanted MSCs into ischemic myocardium, and observed the survival and cardiac protective capacity of MSCs in a rat model of acute myocardial infarction. Furthermore, we tried to explore the underlying mechanisms and the role of Toll-like receptor-4 (TLR4) in the signal pathway of LPS-induced cardiac protection. METHODS AND RESULTS: Acute myocardial infarction model was developed by left anterior descending coronary artery ligation. 60 rats were divided into 4 groups randomly and given an intramyocardial injection of one of the following treatments: 30 microl PBS (control group), 3 x 10(6) wild MSCs/30 microl (wMSCs group), 3 x 10(6) LPS-preconditioned wild MSCs/30 microl (LPS-wMSCs group), or 3 x 10(6) LPS-preconditioned TLR4 gene deleted MSCs/30 microl (LPS-tMSCs group). After 3 weeks, LPS-preconditioned wild MSCs transplantation ameliorated cardiac function and reduced fibrosis of infarcted myocardium. Vascular density was markedly increased in LPS-wMSCs group compared with other three groups. Survival rate of engrafted MSCs was elevated and apoptosis of myocardium was reduced in infarcted heart. Expression of vascular endothelial growth factor (VEGF) and phospho-Akt was increased in the infarcted myocardium after transplantation of LPS-preconditioned MSCs. CONCLUSION: LPS preconditioning enhanced survival of engrafted MSCs, stimulated expression of VEGF and activated PI3K/Akt pathway. LPS preconditioning before MSCs transplantation resulted in superior therapeutic neovascularization and recovery of cardiac function. LPS preconditioning provided a novel strategy in maximizing biologic and functional properties of MSCs.
Asunto(s)
Lipopolisacáridos/farmacología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/efectos de los fármacos , Infarto del Miocardio/cirugía , Receptor Toll-Like 4/fisiología , Animales , División Celular/efectos de los fármacos , Células Cultivadas/efectos de los fármacos , Células Cultivadas/trasplante , Evaluación Preclínica de Medicamentos , Femenino , Supervivencia de Injerto , Lipopolisacáridos/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Proteínas Proto-Oncogénicas c-akt/genética , Distribución Aleatoria , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/deficiencia , Receptor Toll-Like 4/genética , Trasplante Heterólogo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
BACKGROUND: Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up. METHODS AND RESULTS: Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m2 and 1.07 to 1.46 m2, respectively). No signs of valve degeneration were observed in both patients. CONCLUSIONS: TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.
Asunto(s)
Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Monocitos/trasplante , Insuficiencia de la Válvula Pulmonar/cirugía , Válvula Pulmonar/cirugía , Ingeniería de Tejidos , Adolescente , Reactores Biológicos , Diferenciación Celular , Células Cultivadas/citología , Células Cultivadas/trasplante , Niño , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Monocitos/citología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Arteria Pulmonar/anomalías , Válvula Pulmonar/anomalías , Insuficiencia de la Válvula Pulmonar/etiología , Tetralogía de Fallot/cirugía , Ingeniería de Tejidos/instrumentación , Ingeniería de Tejidos/métodos , Trasplante Autólogo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
BACKGROUND: Embryonic stem (ES) cells can terminally differentiate into all types of somatic cells and are considered a promising source of seed cells for tissue engineering. However, despite recent progress in in vitro differentiation and in vivo transplantation methodologies of ES cells, to date, no one has succeeded in using ES cells in tissue engineering for generation of somatic tissues in vitro for potential transplantation therapy. METHODS AND RESULTS: ES-D3 cells were cultured in a slow-turning lateral vessel for mass production of embryoid bodies. The embryoid bodies were then induced to differentiate into cardiomyocytes in a medium supplemented with 1% ascorbic acid. The ES cell-derived cardiomyocytes were then enriched by Percoll gradient centrifugation. The enriched cardiomyocytes were mixed with liquid type I collagen supplemented with Matrigel to construct engineered cardiac tissue (ECT). After in vitro stretching for 7 days, the ECT can beat synchronously and respond to physical and pharmaceutical stimulation. Histological, immunohistochemical, and transmission electron microscopic studies further indicate that the ECTs both structurally and functionally resemble neonatal native cardiac muscle. Markers related to undifferentiated ES cell contamination were not found in reverse transcriptase-polymerase chain reaction analysis of the Percoll-enriched cardiomyocytes. No teratoma formation was observed in the ECTs implanted subcutaneously in nude mice for 4 weeks. CONCLUSIONS: ES cells can be used as a source of seed cells for cardiac tissue engineering. Additional work remains to demonstrate engraftment of the engineered heart tissue in the case of cardiac defects and its functional integrity within the host's remaining healthy cardiac tissue.
Asunto(s)
Implantes Experimentales , Miocitos Cardíacos/trasplante , Organoides/fisiología , Células Madre/citología , Ingeniería de Tejidos/métodos , Animales , Ácido Ascórbico/farmacología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas/citología , Células Cultivadas/efectos de los fármacos , Células Cultivadas/trasplante , Colágeno , Colágeno Tipo I , Combinación de Medicamentos , Embrión de Mamíferos/citología , Glutamina/farmacología , Laminina , Mercaptoetanol/farmacología , Ratones , Ratones Desnudos , Contracción Miocárdica/efectos de los fármacos , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/fisiología , Proteoglicanos , Células Madre/efectos de los fármacos , Estrés Mecánico , Ingeniería de Tejidos/instrumentaciónRESUMEN
BACKGROUND: After a myocardial infarction, the injured region becomes fibrotic and the myocardial scar may expand if the ventricular wall lacks elasticity. Cardiac dilatation may precipitate the vicious cycle of progressive heart failure. The present study evaluated the functional benefits of increasing elastin within a myocardial scar using cell based gene therapy. METHODS AND RESULTS: A myocardial infarction was generated by ligation of the left anterior descending artery in rats. Six days later, 2 x 10(6) syngeneic rat endothelial cells transfected with the rat elastin gene (elastin group, n=14) or an empty plasmid (control group, n=14) were transplanted into the infarct scar. Cardiac function, left ventricular (LV) volume, and infarct size were monitored over 3 months by echocardiography, Langendorff measurements, and planimetry. Elastin deposition was evaluated in the cells and in the infarct region by Western blot assay and by histological examination. Recombinant elastin was found in the scar in the elastin group but not the control group during the 3 months after cell transplantation. Histological assessment demonstrated organized elastic fibers within the infarct region. LV volume and infarct size were significantly smaller (P<0.05) in the elastin group than in the control group. Cardiac function evaluated by echocardiography and during Langendorff perfusion was significantly better (P<0.05) in the elastin group than in the control group. CONCLUSIONS: Expressing recombinant elastin within the myocardial scar reduced scar expansion and prevented LV enlargement after a myocardial infarction. Altering matrix remodeling after an infarct preserved the LV function for at least 3 months.
Asunto(s)
Elastina/fisiología , Células Endoteliales/trasplante , Terapia Genética , Insuficiencia Cardíaca/prevención & control , Infarto del Miocardio/terapia , Función Ventricular Izquierda/fisiología , Animales , Células Cultivadas/metabolismo , Células Cultivadas/trasplante , Cicatriz/metabolismo , Cicatriz/patología , Evaluación Preclínica de Medicamentos , Elastina/genética , Células Endoteliales/metabolismo , Matriz Extracelular/ultraestructura , Insuficiencia Cardíaca/etiología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/prevención & control , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocardio/química , Miocardio/patología , Distribución Aleatoria , Ratas , Ratas Endogámicas Lew , Proteínas Recombinantes de Fusión/análisis , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/fisiología , Método Simple Ciego , Transfección , Ultrasonografía , Remodelación VentricularRESUMEN
In recent years, several groups have reported a variety of strategies for developing biological pacemakers whose ultimate function would be to supplement/replace electronic pacemakers. Strategies have included gene therapy using naked plasmids or viral vectors and cell therapy for which both adult human mesenchymal stem cells (hMSCs) and human embryonic stem cells have been employed. This article reviews the various approaches and summarizes our own research in which the pacemaker gene, HCN2, is administered via viral vector or in an hMSC platform to produce pacemaker function in the intact canine heart.
Asunto(s)
Arritmias Cardíacas/terapia , Estimulación Cardíaca Artificial , Terapia Genética , Canales Iónicos/fisiología , Células Madre Mesenquimatosas/citología , Proteínas Musculares/fisiología , Miocitos Cardíacos/citología , Adenoviridae/genética , Adulto , Animales , Arritmias Cardíacas/genética , Arritmias Cardíacas/patología , Células Cultivadas/efectos de los fármacos , Células Cultivadas/fisiología , Células Cultivadas/trasplante , Técnicas de Cocultivo , Perros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización , Canales Iónicos/administración & dosificación , Células Madre Mesenquimatosas/efectos de los fármacos , Proteínas Musculares/administración & dosificación , Miocitos Cardíacos/efectos de los fármacos , Plásmidos , Canales de Potasio , Trasplante de Células MadreRESUMEN
STUDY DESIGN: Prospective study to assess the enhancement of spine fusion using a tissue engineering construct consisting of bone marrow cells genetically modified by adenovirus (Ad) vector-encoding bone morphogenetic protein-7 (BMP-7) seeded onto an allograft scaffold in a rat model. OBJECTIVES: To evaluate Ad transgene expression at the fusion site and the effect of AdBMP-7-treatment on fusion rates, mechanical stability, microscopic anatomy, and bone formation rates. SUMMARY OF BACKGROUND DATA: Nonunion is a major complication of spine fusion. Gene transfer may be an effective method for locally overexpressing BMP-7, a gene important for bone formation and regeneration to enhance allograft spine fusion. MATERIALS AND METHODS: Bone marrow cells were treated with AdBMP-7 or Adbetagal (encoding the marker gene beta-galactosidase), AdNull (with no gene), or no vector and implanted with allograft in a site of posterior spine fusion. Marker gene expression was assessed up to 14 days after administration. Fusions were evaluated at 8 weeks. RESULTS: Ad gene expression was maximal on day 3, waning to background levels by 14 days. With AdBMP-7 treatment, radiographic fusion rate was 70% and mechanical fusion rate was 80% versus 0% by either parameter in control groups. Fused AdBMP-7-treated spines had a 2.5-fold to 3.0-fold lower range of motion and 1.7-fold to 1.9-fold lower hysteresis than controls. Fusion masses of AdBMP-7-treated spines had the microscopic appearance of normal trabecular bone and showed a 23-fold higher uptake of fluorochrome indicating increased bone formation. CONCLUSIONS: Addition of AdBMP-7-modified marrow cells can enhance allograft spine fusion.
Asunto(s)
Trasplante de Médula Ósea , Proteínas Morfogenéticas Óseas/fisiología , Terapia Genética/métodos , Fusión Vertebral/métodos , Ingeniería de Tejidos/métodos , Factor de Crecimiento Transformador beta/fisiología , Adenoviridae/genética , Animales , Células de la Médula Ósea/metabolismo , Proteína Morfogenética Ósea 7 , Proteínas Morfogenéticas Óseas/genética , Trasplante Óseo , Células Cultivadas/metabolismo , Células Cultivadas/trasplante , Evaluación Preclínica de Medicamentos , Genes Reporteros , Vectores Genéticos/genética , Vectores Genéticos/uso terapéutico , Operón Lac , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/cirugía , Vértebras Lumbares/ultraestructura , Oseointegración , Estudios Prospectivos , Radiografía , Ratas , Ratas Endogámicas Lew , Proteínas Recombinantes de Fusión/fisiología , Factor de Crecimiento Transformador beta/genética , Trasplante Homólogo , Cicatrización de HeridasRESUMEN
Recent advances in bone tissue engineering are established on the understanding of an engineered scaffold, the molecular milieu within the osteogenic site, and the cell(s) predisposed to an osteogenic lineage. Advances in the incorporation of a generative vehicle into a skeletal defect require temporal and spatial distribution of the scaffold, growth factor, and cell compatible with enhanced bone healing. Monitoring events culminating in osteogenesis has focused on phenotypic and intracellular indicators. Phenotypic and intracellular indicators include the presence of receptors and intracellular signals that enable cell proliferation and differentiation. Progress in the areas of scaffold design, growth factor utilization, bone cell lineage, and intracellular signaling are reviewed.
Asunto(s)
Enfermedades Óseas/terapia , Regeneración Ósea , Sustitutos de Huesos/uso terapéutico , Sustancias de Crecimiento/uso terapéutico , Ingeniería de Tejidos , Factor de Crecimiento Transformador beta , Animales , Biopolímeros/uso terapéutico , Proteína Morfogenética Ósea 2 , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/uso terapéutico , Regeneración Ósea/efectos de los fármacos , Regeneración Ósea/fisiología , Células Cultivadas/trasplante , Colágeno/administración & dosificación , Perros , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Evaluación Preclínica de Medicamentos , Terapia Genética , Sustancias de Crecimiento/administración & dosificación , Sustancias de Crecimiento/genética , Haplorrinos , Humanos , Ensayo de Materiales , Ratones , Ratones Noqueados , Ratones Transgénicos , Microesferas , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Conejos , Ratas , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes , Ovinos , Transducción de Señal/efectos de los fármacos , Trasplante de Células Madre , PorcinosRESUMEN
Although ciliary neurotrophic factor (CNTF) is a potent survival factor for many types of neurons and glial cells in vitro, there is currently no evidence that it participates in normal development. Here we show that CNTF greatly enhances the rate of oligodendrocyte generation. Proliferation of oligodendrocyte precursor cells purified from rodent optic nerves and cultured in platelet-derived growth factor-containing medium is significantly increased by CNTF. Similarly, the number of proliferating oligodendrocyte precursor cells in developing optic nerves of transgenic mice lacking CNTF is decreased by up to threefold and the number of oligodendrocytes is transiently decreased; proliferation is restored to normal by the delivery of exogenous CNTF into the developing optic nerve. Both oligodendrocyte number and myelination ultimately attain wild-type values in CNTF-deficient adult mice, indicating that CNTF is not necessary for either oligodendrocyte differentiation or myelination, although it normally accelerates oligodendrocyte development by enhancing the proliferation of oligodendrocyte precursor cells.
Asunto(s)
Proteínas del Tejido Nervioso/farmacología , Oligodendroglía/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas/trasplante , Factor Neurotrófico Ciliar , Cisteína/farmacología , ADN/análisis , ADN Complementario/genética , Ratones , Ratones Noqueados , Vaina de Mielina/fisiología , Proteínas del Tejido Nervioso/deficiencia , Proteínas del Tejido Nervioso/genética , Oligodendroglía/metabolismo , Nervio Óptico/citología , Ratas , Células Madre/citología , Células Madre/efectos de los fármacos , Espacio Subaracnoideo , TransfecciónRESUMEN
Hematopoietic stem cells from sources other than medullary bone marrow are being used for experimental and clinical rescue following myeloablative therapy. In this paper we review the cells capable of bone marrow engraftment and the use of orthotopic, cadaveric, peripheral blood, umbilical cord blood, and fetal liver derived stem cells in transplantation.
Asunto(s)
Transfusión de Sangre Autóloga/métodos , Trasplante de Médula Ósea/métodos , Células Madre Hematopoyéticas , Células Sanguíneas , Células de la Médula Ósea , Cadáver , Trasplante de Células , Células Cultivadas/trasplante , Sangre Fetal/citología , Trasplante de Tejido Fetal , Enfermedad Injerto contra Huésped/prevención & control , Hematopoyesis/efectos de los fármacos , Factores de Crecimiento de Célula Hematopoyética/farmacología , Humanos , Recién Nacido , Hígado/citología , Hígado/embriología , Proteínas Recombinantes/farmacologíaAsunto(s)
Transfusión de Componentes Sanguíneos , Transfusión de Sangre Autóloga , Trasplante de Células Madre Hematopoyéticas , Animales , Enfermedades de la Médula Ósea/terapia , Células Cultivadas/trasplante , Factores Estimulantes de Colonias/farmacología , Perros , Predicción , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Interleucinas/farmacología , RatonesRESUMEN
Hematopoietic stem cells circulate in the peripheral blood. These cells can be collected by apheresis techniques either in the unperturbed state, after mobilization following the administration of cytokines like G-CSF or GM-CSF, or during the phase of early blood count recovery following chemotherapy-induced myelosuppression. The number of cells collected following mobilization is greater than that obtained after apheresis in the unperturbed state. There are, however, qualitative differences between unperturbed and mobilized cells. Chemotherapy related mobilization can be potentially dangerous in that severe myelosuppression necessary to achieve mobilization can have serious consequences. There are no controlled studies that evaluate the relative merits of each method of collection. Regardless of the techniques employed peripheral blood stem cells can reliably accelerate hematologic recovery after potentially myeloblative therapy and provide an alternative to bone marrow support.