RESUMEN
Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9-T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Traumatismos de la Médula Espinal/terapia , Adulto , Animales , Técnicas de Cocultivo , Femenino , Ganglios Espinales , Miembro Posterior , Humanos , Ácido Láctico , Lipopolisacáridos , Locomoción , Masculino , Células Madre Mesenquimatosas , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ratas Sprague-Dawley , Recuperación de la Función , Traumatismos de la Médula Espinal/fisiopatología , Andamios del TejidoRESUMEN
OBJECTIVE: To observe the clinical effect on site preservation with self platelet-rich fibrin (PRF) in posterior dental areas after extraction.â© METHODS: Thirty patients who asked to extract posterior teeth and were ready for dental implantation were enrolled. PRF was implanted immediately in alveolar fossa after extraction. Cone beam computer tomography (CBCT) images were taken after 4-6 months and the changes in height and width of alveolar bone were observed.â© RESULTS: There was no statistical difference in the height and width between the alveolar bone treated with PRF after the extraction of tooth and the bone condition before the extraction of tooth.â© CONCLUSION: The site preservative technology with PRF could maintain the mass of alveolar bone in posterior dental areas, which provide a better bone condition for later dental implantation.
Asunto(s)
Proceso Alveolar , Fibrina/uso terapéutico , Extracción Dental , Plaquetas , Tomografía Computarizada de Haz Cónico , Implantación Dental , HumanosRESUMEN
Therapeutic impact of neural stem cells (NSCs) for acute spinal cord injury (SCI) has been limited by the rapid loss of donor cells. Neuroinflammation is likely the cause. As there are close temporal-spatial correlations between the inducible nitric oxide (NO) synthase expression and the donor NSC death after neurotrauma, we reasoned that NO-associated radical species might be the inflammatory effectors which eliminate NSC grafts and kill host neurons. To test this hypothesis, human NSCs (hNSCs: 5 x 10(4) to 2 x 10(6) per milliliter) were treated in vitro with "plain" medium, 20 microM glutamate, or donors of NO and peroxynitrite (ONOO(-); 100 and 400 microM of spermine or DETA NONOate, and SIN-1, respectively). hNSC apoptosis primarily resulted from SIN-1 treatment, showing ONOO(-)-triggered protein nitration and the activation of p38 MAPK, cytochrome c release, and caspases. Therefore, cell death following post-SCI (p.i.) NO surge may be mediated through conversion of NO into ONOO(-). We subsequently examined such causal relationship in a rat model of dual penetrating SCI using a retrievable design of poly-lactic-co-glycolic acid (PLGA) scaffold seeded with hNSCs that was shielded by drug-releasing polymer. Besides confirming the ONOO(-)-induced cell death signaling, we demonstrated that cotransplantation of PLGA film embedded with ONOO(-) scavenger, manganese (III) tetrakis (4-benzoic acid) porphyrin, or uric acid (1 micromol per film), markedly protected hNSCs 24 hours p.i. (total: n = 10). Our findings may provide a bioengineering approach for investigating mechanisms underlying the host microenvironment and donor NSC interaction and help formulate strategies for enhancing graft and host cell survival after SCI.
Asunto(s)
Sistemas de Liberación de Medicamentos , Depuradores de Radicales Libres/administración & dosificación , Glicolatos/metabolismo , Neuronas/citología , Ácido Peroxinitroso/toxicidad , Traumatismos de la Médula Espinal/terapia , Células Madre/citología , Enfermedad Aguda , Animales , Anexina A5/metabolismo , Western Blotting , Caspasas/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular , Citoprotección/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Fluoresceínas/metabolismo , Depuradores de Radicales Libres/farmacología , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Ácido Láctico , Neuronas/efectos de los fármacos , Óxido Nítrico/metabolismo , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ratas , Transducción de Señal , Traumatismos de la Médula Espinal/patología , Células Madre/efectos de los fármacos , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
Our earlier work generated a powerful platform technology of polymeric scaffolding of stem cells to investigate and treat the injured or diseased central nervous system. However, the reciprocal sequelae between biophysical properties of the polymer and responses of the stem cell have not been examined in situ in lesioned spinal cords. We postulated that implantable synthetic scaffolds, acting through physical features, might affect donor cell behavior and host tissue remodeling. To test this hypothesis, poly(d,l-lactic-co-glycolic acid) (PLGA) in either low/soft or high/hard rigidity was fabricated for carrying adult human bone marrow mesenchymal stromal stem cells (hMSCs). The construct was transplanted into the epicenter of a rat model of acute T9-10 segmental hemisection to evaluate the effect of PLGA rigidity on the therapeutic potential and fate of hMSCs for neural repair. Compared to controls, only treatment with soft PLGA-scaffolded hMSCs significantly improved sensorimotor function via activation of recovery neurobiology mechanisms. The main benefits included inhibiting neuroinflammation and enhancing tissue protection. Also detected in the treated lesion region were expressions of neurotrophic and anti-inflammatory factors together with proliferation of endogenous neural stem cells, impacts likely derived from hMSCs' functional multipotency maintained by soft PLGA-scaffolding. Conversely, hard rigidity PLGA activated mechanotransduction and mesoderm lineage differentiation of hMSCs that ectopically produced bone, cartilage and muscle markers in neural parenchyma. The findings collectively suggested that the physical texture of polymeric scaffolds should be tailored for sustaining the stemness of hMSCs to constructively interact with the spinal cord for functional restoration.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas/métodos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Traumatismos de la Médula Espinal , Andamios del Tejido/química , Animales , Femenino , Humanos , Ratas , Ratas Sprague-DawleyRESUMEN
With the assistance of an ink-jet printer, solvent (the "ink") can be controllably and reproducibly printed onto electrospun nanofiber meshes (the "paper") to generate various micropatterns and subsequently guide distinct cellular organization and phenotype expression. In combination with the nanofiber-assisted layer-by-layer cell assembly, the patterned electrospun meshes will define an instructive microenvironment for guided tissue formation.
Asunto(s)
Nanofibras/química , Colágeno/química , Colágeno/metabolismo , Diseño Asistido por Computadora , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Poliésteres/química , Albúmina Sérica Bovina/químicaRESUMEN
Immediate-implant-immediate-loading restoration exhibits many advantages, such as recovery appearance, early function, short implant period, reduced operation frequency and trauma, and less pain, among others. This report introduced a case of immediate-implant-immediate-loading restoration failure because of implant neck split.