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1.
Arthroscopy ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33621646

RESUMO

PURPOSE: To compare the time-zero tibiofemoral contact mechanics among the four different suturing repairs: transtibial pullout suture repair, suture anchor repair, side-to-side repair, and H-plasty repair. METHODS: Twenty-four human cadaveric knees were included. Each lateral meniscus condition (intact, radial tear, and repair) was tested under a 1000-N axial compressive load at 0°, 30°, 60°, and 90° of flexion. Four different repair techniques: transtibial pullout, suture anchor, side-to-side, and H-plasty repair technique were tested. Tibiofemoral mean and peak contact pressure and contact area in the lateral and medial compartments were measured by Tekscan sensors. RESULTS: Radial tears adjacent to the posterior lateral meniscus root produced significantly decreased contact area and increased mean and peak contact pressures in the lateral compartment across all angles (P < 0.05). All repair groups could improve the contact mechanics relative to the torn condition (P < 0.05), but only H-plasty repair showed no significant difference in the mean and peak contact pressure and contact area comparing with that of the intact state at all flexion angles (P > 0.05). CONCLUSIONS: The results showed that the tibiofemoral contact mechanics after adjacent radial tears of the posterior lateral meniscal root were improved to the intact level by H-plasty repair at time-zero. The additional vertical mattress sutures act as "stabilizers" to provide a more stable environment in distributing vertical tibiofemoral pressure. The other three repair techniques also significantly improved lateral tibiofemoral contact mechanics relative to the corresponding tear conditions.

2.
Arthroscopy ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33227321

RESUMO

PURPOSE: The purpose of this study was to compare tibiofemoral contact mechanics after horizontal or ripstop (horizontal plus vertical) sutures in inside-out and transtibial repair for meniscal radial tears with 10 porcine knees each group. METHODS: Ten matched pairs of porcine knees were tested under a 1500-N axial compressive load at 0°, 30°, 60°, and 90° of knee flexion. Each knee underwent four testing conditions consecutively: (1) intact, (2) medial meniscal radial tear, (3) horizontal suture repair configuration, and (4) ripstop suture repair configuration. Tekscan sensors measured tibiofemoral contact pressure and contact area in the medial and lateral compartments. RESULTS: All repair groups improved the contact mechanics when compared with the tear state among all flexion angles analyzed (all P < 0.05). Furthermore, ripstop sutures with both inside-out and transtibial repairs restored intact knee contact area and pressures (peak and mean) in the medial compartment at all flexion angles while the horizontal sutures alone failed to do so for contact pressures at 60° and 90° and for contact surface areas at all flexion angles. However, the aforementioned parameters were not significantly different between inside-out sutures and transtibial sutures, regardless of horizontal or ripstop configuration (P > 0.05). CONCLUSIONS: Radial tears of the meniscus in a porcine model significantly decreased medial contact area and increased mean and peak contact pressure. Both inside-out and transtibial ripstop repairs for radial tears aid in restoring intact tibiofemoral contact mechanics at all assessed knee flexion angles.

3.
Knee ; 27(5): 1560-1566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33010774

RESUMO

BACKGROUND: Several suture repair techniques have been reported for radial tear close to the posterior lateral meniscal root (type II PLMRT). However, no study has evaluated the clinical results after repair using the FasT-Fix system. This paper describes a novel H-plasty surgical repair technique and reports its clinical results. METHODS: From January 2015 to January 2017, 47 patients underwent repair of type II PLMRT with concomitant anterior cruciate ligament reconstruction and were included in this study. Assessments performed preoperatively and at final follow-up included the Lysholm score, subjective International Knee Documentation Committee (IKDC) score, and knee stability assessments (pivot-shift test, Lachman test, KNEELAX arthrometer side-to-side difference). Magnetic resonance imaging was used to compare the lateral meniscal extrusion pre- versus postoperatively. Second-look arthroscopy was performed to evaluate the meniscal healing in 38 cases. RESULTS: Forty-seven patients were followed up for an average of 30.7 months (range 18-46 months). No patients experienced meniscal mechanical symptoms. At final follow-up, there were significant improvements in the Lysholm score, IKDC score, knee stability assessments, and lateral meniscal extrusion compared with the preoperative values. In the 38 of 47 patients that underwent second-look arthroscopy after an average of 17.5 months (range 14-19 months), all repairs (100%) were completely healed. CONCLUSIONS: The novel H-plasty repair using the FasT-Fix system was an effective surgical treatment for type II PLMRT. Considering the satisfactory clinical results and the convenience of the surgery, H-plasty repair is recommended to be used preferentially.

4.
Arthroscopy ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32911005

RESUMO

PURPOSE: To introduce an all-inside modified Broström technique to suture the anterior talofibular ligament (ATFL) and inferior extensor retinaculum (IER) under arthroscopy and to compare its outcomes with those of the conventional open procedure. METHODS: All patients who underwent arthroscopic or open repair of the ATFL between June 2014 and December 2017 were included in this study. Visual analog scale (VAS), Karlsson and Peterson (K-P), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot, and Tegner activity scores, as well as manual anterior drawer test (ADT), were used to evaluate the patients preoperatively and ≥2 years after surgery. The Sefton grading system was used to assess the level of satisfaction after surgery. Detailed surgical data and intraoperative findings were documented at the time of surgery. RESULTS: A total of 67 patients, 31 in the arthroscopic group and 36 in the open group, were included in this study (43 men and 24 women, mean body mass index 24.00, range 19.53 to 30.03). The surgical duration in the arthroscopic group (median, 34 minutes; range, 25 to 74) was significantly shorter than that in the open group (mean, 43.08 ± 8.11 minutes; 95% confidence interval [CI] 40.34 to 45.83) (P = .007). At the last follow-up, the subjective functional scores and ADT results improved significantly in both cohorts (P < .001). However, no significant difference was found in the VAS score (1.74 ± 1.24, 95% CI 1.29 to 2.2, in the open group versus 1.58 ± 1.2, 95% CI 1.18 to 1.99, in the arthroscopic group; P = .581), AOFAS score (91.71 ± 5.46, 95% CI 89.71 to 93.71, versus 90.67 ± 5.59, 95% CI 88.78 to 92.56; P = .444), K-P score (87.52 ± 7.59, 95% CI 84.73 to 90.3, versus 88.75 ± 5.56, 95% CI 86.87 to 90.63; P = .446), and ADT evaluation (normal: 96.77% versus 94.44%, P = .557) between the arthroscopic and open groups, respectively. In addition, 28 cases (90.32%) in the arthroscopic group and 32 (88.89%) in the open group achieved satisfactory results based on the Sefton grading system (P = .736). Seventeen patients (47.2%) in the open group and 18 patients (58.1%) in the arthroscopic group underwent Tegner evaluation after surgery, which showed no significant difference (5, interquartile range [IQR] 1 in the open group versus 5, IQR 3 in the arthroscopic group; P = .883). Complications were reported in 4 (11.1%) and 2 (6.5%) patients who underwent open and arthroscopic surgeries, respectively (P = .813). CONCLUSIONS: Both open and arthroscopic modified Broström surgeries generated favorable outcomes, with a significant improvement compared with the preoperative condition. Compared with the open Broström-Gould procedure, the all-inside arthroscopic modified Broström technique produced equivalent functional and clinical results at a minimum of 2 years after the operation, with a shorter surgical duration. Arthroscopic repair might be a safe and viable alternative to open surgery for lateral ankle stabilization. LEVEL OF EVIDENCE: III.

5.
Adv Mater ; 31(49): e1904341, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31621958

RESUMO

Current approaches to fabrication of nSC composites for bone tissue engineering (BTE) have limited capacity to achieve uniform surface functionalization while replicating the complex architecture and bioactivity of native bone, compromising application of these nanocomposites for in situ bone regeneration. A robust biosilicification strategy is reported to impart a uniform and stable osteoinductive surface to porous collagen scaffolds. The resultant nSC composites possess a native-bone-like porous structure and a nanosilica coating. The osteoinductivity of the nSC scaffolds is strongly dependent on the surface roughness and silicon content in the silica coating. Notably, without the use of exogenous cells and growth factors (GFs), the nSC scaffolds induce successful repair of a critical-sized calvarium defect in a rabbit model. It is revealed that topographic and chemical cues presented by nSC scaffolds could synergistically activate multiple signaling pathways related to mesenchymal stem cell recruitment and bone regeneration. Thus, this facile surface biosilicification approach could be valuable by enabling production of BTE scaffolds with large sizes, complex porous structures, and varied osteoinductivity. The nanosilica-functionalized scaffolds can be implanted via a cell/GF-free, one-step surgery for in situ bone regeneration, thus demonstrating high potential for clinical translation in treatment of massive bone defects.


Assuntos
Regeneração Óssea , Colágeno/química , Nanoestruturas/química , Dióxido de Silício/química , Tecidos Suporte/química , Animais , Materiais Biomiméticos/química , Biomimética , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Células-Tronco Mesenquimais/citologia , Nanoestruturas/ultraestrutura , Osteogênese , Porosidade , Coelhos , Crânio/lesões , Crânio/fisiologia
6.
Sci Transl Med ; 11(487)2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971451

RESUMO

Reconstruction of the anisotropic structure and proper function of the knee meniscus remains an important challenge to overcome, because the complexity of the zonal tissue organization in the meniscus has important roles in load bearing and shock absorption. Current tissue engineering solutions for meniscus reconstruction have failed to achieve and maintain the proper function in vivo because they have generated homogeneous tissues, leading to long-term joint degeneration. To address this challenge, we applied biomechanical and biochemical stimuli to mesenchymal stem cells seeded into a biomimetic scaffold to induce spatial regulation of fibrochondrocyte differentiation, resulting in physiological anisotropy in the engineered meniscus. Using a customized dynamic tension-compression loading system in conjunction with two growth factors, we induced zonal, layer-specific expression of type I and type II collagens with similar structure and function to those present in the native meniscus tissue. Engineered meniscus demonstrated long-term chondroprotection of the knee joint in a rabbit model. This study simultaneously applied biomechanical, biochemical, and structural cues to achieve anisotropic reconstruction of the meniscus, demonstrating the utility of anisotropic engineered meniscus for long-term knee chondroprotection in vivo.


Assuntos
Menisco/anatomia & histologia , Menisco/fisiologia , Engenharia Tecidual , Animais , Anisotropia , Fenômenos Biomecânicos , Cartilagem/patologia , Diferenciação Celular , Condrócitos/citologia , Análise de Elementos Finitos , Regulação da Expressão Gênica , Articulações/patologia , Masculino , Coelhos , Regeneração , Tecidos Suporte/química
7.
Am J Sports Med ; 47(4): 954-967, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30786213

RESUMO

BACKGROUND: Although many strategies have been developed to modify the biological and biomechanical environment of the meniscal suture repair to improve the chances of healing, the failure rates remain high. Thus, new methods to promote meniscal regeneration and repair are needed. HYPOTHESIS: Administration of magnesium (via a repair using magnesium stitches) might enhance recruitment and adherence of endogenous stem cells to the site of the lesion, thereby promoting in situ meniscal regeneration and chondroprotective functions. STUDY DESIGN: Controlled laboratory study. METHODS: Synovial fluid-derived mesenchymal stem cells (SMSCs) were identified and isolated from the knees of rabbits with a meniscal injury of 4 weeks' duration. An in vitro analysis of adherence and chemotaxis of SMSCs was performed. For the in vivo assay, rabbits (n = 120) with meniscal lesions were divided into 3 groups: repair with high-purity magnesium stitches (Mg group), repair with absorbable sutures (Control group), and no repair (Blank group). Healing of the regenerated tissue and degeneration of the articular cartilage were evaluated by gross and histological analysis at postoperative weeks 1, 3, 6, and 12. The mechanical properties of the repaired meniscus were also analyzed (tensile testing). RESULTS: In vitro, magnesium promoted the adhesion and migration of SMSCs, which were identified and increased in the knee joints with meniscal lesions. Moreover, fibrochondrogenesis of SMSCs was stimulated by magnesium. Compared with the other groups, the Mg group had enhanced tissue regeneration, lower cartilage degeneration, and retained mechanical strength at 12 weeks after meniscal repair. CONCLUSION/CLINICAL RELEVANCE: Magnesium could be used for in situ meniscal repair due to the potential capacity of magnesium to recruit endogenous stem cells and promote synthesis of fibrocartilaginous matrix.


Assuntos
Magnésio/administração & dosagem , Meniscos Tibiais/fisiologia , Meniscos Tibiais/cirurgia , Células-Tronco/fisiologia , Suturas , Cicatrização/fisiologia , Animais , Cartilagem Articular/fisiologia , Masculino , Estudo de Prova de Conceito , Coelhos , Regeneração
8.
Artigo em Inglês | MEDLINE | ID: mdl-31915446

RESUMO

Acute liver failure (ALF) is a serious life-threatening condition. Mesenchymal stem cells (MSCs) may be an effective treatment for this condition and a good alternative to liver transplantation. Icaritin (ICT) is an active ingredient of the genus Epimedium, a traditional Chinese medicine, with the potential to enhance the proliferation of MSCs. The purpose of this study was to explore whether ICT increased the therapeutic effects of MSCs and explore its underlying mechanisms. For in vivo experiments, a rat ALF model was established by intraperitoneal injection of D(+)-galactosamine/ lipopolysaccharide. MSCs cocultured with ICT were used to treat ALF rats and the protective effects assessed as survival rate, levels of serum AST and ALT, and histological changes in liver tissue. For in vitro experiments, MSCs were treated in serum-free culture for 72 h to simulate the disruption of intrahepatic microcirculation. MSCs apoptosis was examined to determine whether ICT rescued impaired MSCs. The role of the hepatocyte growth factor (HGF)/c-Met pathway in MSCs was assessed by constructing genetically modified MSCs overexpressing c-Met and by using the c-Met receptor inhibitor (crizotinib). The results showed that MSCs increased the survival rate of ALF rats and reduced liver damage. MSCs cocultured with ICT exerted a greater therapeutic effect than MSCs alone. Further, the HGF/c-Met pathway played a key role in the antiapoptotic activity of MSCs, which was associated with the optimized efficacy of ICT. In conclusion, this study demonstrated that ICT enhances the therapeutic effect of MSCs in a model of ALF, improving the antiapoptotic potential of MSCs by upregulation of the HGF/c-Met pathway. The combination of stem cell therapy with traditional herbal extracts may improve MSC-based clinical applications.

9.
Sci Rep ; 8(1): 9041, 2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-29899552

RESUMO

Meniscal allograft transplantation yields good and excellent results but is limited by donor availability. The purpose of the study was to evaluate the effectiveness of radiated deep-frozen xenogenic meniscal tissue (RDF-X) as an alternative graft choice in meniscal transplantation. The xenogenic meniscal tissues were harvested from the inner 1/3 part of the porcine meniscus and then irradiated and deeply frozen. The medial menisci of rabbits were replaced by the RDF-X. Meniscal allograft transplantation, meniscectomy and sham operation served as controls. Only a particular kind of rabbit-anti-pig antibody (molecular ranging 60-80 kD) was detected in the blood serum at week 2. The menisci of the group RDF-X grossly resembled the native tissue and the allograft meniscus with fibrocartilage regeneration at postoperative 1 year. Cell incorporation and the extracellular matrix were mostly observed at the surface and the inner 1/3 part of the newly regenerated RDF-X, which was different from the allograft. The biomechanical properties of the group RDF-X were also approximate to those of the native meniscus except for the compressive creep. In addition, chondroprotection was achieved after the RDF-X transplantation although the joint degeneration was not completely prevented. To conclude, the RDF-X could be a promising alternative for meniscal transplantation with similar tissue regeneration capacity to allograft transplantation and superior chondroprotection. The potential minor immunological rejection should be further studied before its clinical application.


Assuntos
Meniscos Tibiais/cirurgia , Menisco/transplante , Regeneração , Membrana Sinovial/fisiopatologia , Animais , Cartilagem Articular/fisiopatologia , Cartilagem Articular/cirurgia , Criopreservação/métodos , Humanos , Meniscos Tibiais/fisiopatologia , Menisco/ultraestrutura , Microscopia Eletrônica de Varredura , Coelhos , Suínos , Transplante Heterólogo
10.
J Pharm Biomed Anal ; 150: 377-385, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29287265

RESUMO

Farfarae Flos (FF) is widely used for the treatment of cough, bronchitis, and asthmatic disorders in the Traditional Chinese Medicine (TCM). According to the experience of TCM, only the flower bud can be used as herbal drug, and its medicinal quality becomes lower after blooming. However, the underlying scientific basis for this phenomenon is not fully understood. In this study, the chemical components and the bioactivities of the FF collected at three different development stages were compared systematically. NMR based fingerprint coupled with multivariate analysis showed that the flower buds differed greatly from the fully opened flower both on the secondary and primary metabolites, and the animal experiments showed that the fully opened flower exhibited no antitussive or expectorant effect. In addition, the endogenous metabolites correlated with the antitussive and expectorant effect of FF were also identified. These findings are useful for understanding the rationality of the traditional use of FF, and also suggested the components responsible for the antitussive and expectorant effect of FF.


Assuntos
Antitussígenos/farmacologia , Tosse/prevenção & controle , Expectorantes/farmacologia , Metabolômica/métodos , Extratos Vegetais/farmacologia , Espectroscopia de Prótons por Ressonância Magnética , Tussilago/metabolismo , Hidróxido de Amônia , Animais , Antitussígenos/isolamento & purificação , Tosse/induzido quimicamente , Tosse/fisiopatologia , Modelos Animais de Doenças , Expectorantes/isolamento & purificação , Feminino , Flores/metabolismo , Masculino , Camundongos Endogâmicos ICR , Análise Multivariada , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Tussilago/crescimento & desenvolvimento
11.
J Gene Med ; 19(9-10)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28940489

RESUMO

BACKGROUND: Immunoglobulin (Ig)A antibody of Epstein-Barr virus (EBV) was found to associate with breast cancer (BC), whereas IgA positivity was related to a series of genetic markers in the genes of homologous recombination repair system (HRRs). We assessed the associations of the polymorphisms in HRR genes with the risk and survival of BC. METHODS: A case-control study was conducted with 1551 bc cases and 1605 age-matched healthy controls between October 2008 and March 2012 in the Guangzhou Breast Cancer Study (GZBCS), China, and the case population were followed up until 31 January 2016. Five single nucleotide polymorphisms of candidate genes in HRR system were genotyped. Odds ratios (ORs) and hazards ratios (HRs) were calculated using multivariate logistic regression and Cox proportional hazards regression to estimate the risk and prognostic effect, respectively. RESULTS: RFC1 rs6829064 (AA) was associated with an increased BC risk [OR = 1.35; 95% confidence interval (CI) = 1.06-1.73] compared to the wild genotype (GG). NRM rs1075496 (GT/TT versus GG) was associated with a worse progression-free survival (PFS) and the HR was 1.34 (95% CI = 1.01-1.78), particularly among advanced patients. LIG3 rs1052536 (CT/TT versus CC) was associated with a better PFS and the HR was 0.70 (95% CI = 0.53-0.93). However, RAD54L rs1710286 and RPA1 rs11078676 were not observed to be associated with either the risk or survival of BC. CONCLUSIONS: The findings of the present study suggest that the polymorphisms in HRR genes were associated with BC risk (RFC1 rs6829064) and prognosis (NRM rs1075496 and LIG3 rs1052536), whereas RAD54L rs1710286 and RPA1 rs11078676 had null associations with BC.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Polimorfismo de Nucleotídeo Único , Reparo de DNA por Recombinação/genética , Alelos , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Heterogeneidade Genética , Genótipo , Humanos , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Risco
12.
Chin J Nat Med ; 15(8): 631-640, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28939026

RESUMO

It recently becomes an important and urgent mission for modern scientific research to identify and explain the theory of traditional Chinese medicine (TCM), which has been utilized in China for more than four millennia. Since few works have been contributed to understanding the TCM theory, the mechanism of actions of drugs with cold/hot properties remains unclear. In the present study, six kinds of typical herbs with cold or hot properties were orally administered into mice, and serum and liver samples were analyzed using an untargeted nuclear magnetic resonance (NMR) based metabolomics approach coupled with similarity analysis. This approach was performed to identify and quantify changes in metabolic pathways to elucidate drug actions on the treated mice. Our results showed that those drugs with same property exerted similar effects on the metabolic alterations in mouse serum and liver samples, while drugs with different property showed different effects. The effects of herbal medicines with cold/hot properties were exerted by regulating the pathways linked to glycometabolism, lipid metabolism, amino acids metabolism and other metabolic pathways. The results elucidated the differences and similarities of drugs with cold/hot properties, providing useful information on the explanation of medicinal properties of these TCMs.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Soro/metabolismo , Animais , Fígado/química , Masculino , Medicina Tradicional Chinesa , Metabolômica , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Plantas Medicinais/química , Soro/química , Soro/efeitos dos fármacos
13.
Am J Sports Med ; 45(7): 1497-1511, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28278383

RESUMO

BACKGROUND: Total meniscectomy leads to knee osteoarthritis in the long term. The poly(ε-caprolactone) (PCL) scaffold is a promising material for meniscal tissue regeneration, but cell-free scaffolds result in relatively poor tissue regeneration and lead to joint degeneration. HYPOTHESIS: A novel, 3-dimensional (3D)-printed PCL scaffold augmented with mesenchymal stem cells (MSCs) would offer benefits in meniscal regeneration and cartilage protection. STUDY DESIGN: Controlled laboratory study. METHODS: PCL meniscal scaffolds were 3D printed and seeded with bone marrow-derived MSCs. Seventy-two New Zealand White rabbits were included and were divided into 4 groups: cell-seeded scaffold, cell-free scaffold, sham operation, and total meniscectomy alone. The regeneration of the implanted tissue and the degeneration of articular cartilage were assessed by gross and microscopic (histological and scanning electron microscope) analysis at 12 and 24 weeks postoperatively. The mechanical properties of implants were also evaluated (tensile and compressive testing). RESULTS: Compared with the cell-free group, the cell-seeded scaffold showed notably better gross appearance, with a shiny white color and a smooth surface. Fibrochondrocytes with extracellular collagen type I, II, and III and proteoglycans were found in both seeded and cell-free scaffold implants at 12 and 24 weeks, while the results were significantly better for the cell-seeded group at week 24. Furthermore, the cell-seeded group presented notably lower cartilage degeneration in both femur and tibia compared with the cell-free or meniscectomy group. Both the tensile and compressive properties of the implants in the cell-seeded group were significantly increased compared with those of the cell-free group. CONCLUSION: Seeding MSCs in the PCL scaffold increased its fibrocartilaginous tissue regeneration and mechanical strength, providing a functional replacement to protect articular cartilage from damage after total meniscectomy. CLINICAL RELEVANCE: The study suggests the potential of the novel 3D PCL scaffold augmented with MSCs as an alternative meniscal substitution, although this approach requires further improvement before being used in clinical practice.


Assuntos
Cartilagem Articular/cirurgia , Meniscos Tibiais/cirurgia , Transplante de Células-Tronco Mesenquimais/instrumentação , Poliésteres/farmacologia , Impressão Tridimensional , Engenharia Tecidual/instrumentação , Tecidos Suporte , Animais , Cartilagem Articular/fisiologia , Masculino , Meniscos Tibiais/fisiologia , Impressão Tridimensional/instrumentação , Coelhos , Engenharia Tecidual/métodos
14.
Oncotarget ; 8(64): 108108-108117, 2017 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-29296227

RESUMO

Interleukin 15 (IL-15) is a cytokine exhibiting antitumor characteristic similar to that of IL-2. However, in human tissues and cells, IL-15 expression and secretion is very limited, suggesting IL-15 functions mainly intracellularly. In the present study, we assessed the effects of transfecting NCI-H446 small cell lung cancer cells with genes encoding three IL-15 variants: prototypical IL-15, mature IL-15 peptide, and modified IL-15 in which the IL-2 signal peptide is substituted for the native signal peptide. NCI-H446 cells transfected with empty plasmid served as the control group. We found that IL-15 transfection effectively inhibited NCI-H446 cell proliferation and arrested cell cycle progression, with the modified IL-15 carrying the IL-2 signal peptide exerting the greatest effect. Consistent with those findings, expression each of the three IL-15 variants reduced growth of NCI-H446 xenograph tumors, and the modified IL-15 again showed the greatest effect. In addition, IL-15 expression led to down-regulation of the positive cell cycle regulators cyclin E and CDK2 and up-regulation of the negative cycle regulators p21 and Rb. These findings suggest IL-15 acts as a tumor suppressor that inhibits tumor cell proliferation by inducing cell cycle arrest.

15.
Sci Rep ; 6: 38685, 2016 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-27924854

RESUMO

Bone regeneration required suitable scaffolding materials to support the proliferation and osteogenic differentiation of bone-related cells. In this study, a kind of hybridized nanofibrous scaffold material (CNF/BG) was prepared by incorporating bioactive glass (BG) nanoparticles into carbon nanofibers (CNF) via the combination of BG sol-gel and polyacrylonitrile (PAN) electrospinning, followed by carbonization. Three types (49 s, 68 s and 86 s) of BG nanoparticles were incorporated. To understand the mechanism of CNF/BG hybrids exerting osteogenic effects, bone marrow mesenchymal stromal cells (BMSCs) were cultured directly on these hybrids (contact culture) or cultured in transwell chambers in the presence of these materials (non-contact culture). The contributions of ion release and contact effect on cell proliferation and osteogenic differentiation were able to be correlated. It was found that the ionic dissolution products had limited effect on cell proliferation, while they were able to enhance osteogenic differentiation of BMSCs in comparison with pure CNF. Differently, the proliferation and osteogenic differentiation were both significantly promoted in the contact culture. In both cases, CNF/BG(68 s) showed the strongest ability in influencing cell behaviors due to its fastest release rate of soluble silicium-relating ions. The synergistic effect of CNF and BG would make CNF/BG hybrids promising substrates for bone repairing.


Assuntos
Carbono , Vidro , Células-Tronco Mesenquimais/citologia , Nanofibras , Nanopartículas , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Regeneração Óssea , Carbono/química , Diferenciação Celular , Sobrevivência Celular , Perfilação da Expressão Gênica , Vidro/química , Teste de Materiais , Células-Tronco Mesenquimais/metabolismo , Nanofibras/química , Nanofibras/ultraestrutura , Nanopartículas/química , Nanopartículas/ultraestrutura , Osteogênese , Ratos , Tecidos Suporte
16.
Sci Rep ; 6: 36400, 2016 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-27821864

RESUMO

As a cell source with large quantity and easy access, peripheral blood mesenchymal stem cells (PBMSCs) were isolated and seeded in porcine demineralized cancellous bone (DCB) scaffolds, cultured in chondrogenic medium and evaluated for in vitro chondrogenesis. Bone marrow MSCs (BMMSCs) and articular cartilage chondrocytes (ACCs) underwent the same process as controls. The morphology, viability and proliferation of PBMSCs in DCB scaffolds were similar to those of BMMSCs and ACCs. PBMSCs and BMMSCs showed similar chondrogenesis potential with consistent production of COL 2 and SOX 9 protein and increased COL 2 and AGC mRNA expressions at week 3 but the COL 2 protein production was still less than that of ACCs. Minimal increase of hypertrophic markers was found in all groups. Relatively higher ALP and lower COL 10 mRNA expressions were found in both MSCs groups at week 3 than that in ACCs, whereas no significant difference of COL 1 and SOX 9 mRNA and MMP 13 protein was found among all groups. To conclude, PBMSCs shared similar proliferation and chondrogenic potential with BMMSCs in DCB scaffolds and could be an alternative to BMMSCs for cartilage tissue engineering. Further optimization of chondrogenesis system is needed regardless of the promising results.


Assuntos
Osso Esponjoso/citologia , Condrogênese , Células-Tronco Mesenquimais/citologia , Células-Tronco de Sangue Periférico/citologia , Animais , Técnicas de Cultura de Células , Proliferação de Células , Células Cultivadas , Condrócitos/citologia , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Suínos , Engenharia Tecidual/métodos , Tecidos Suporte
17.
Acta Biomater ; 43: 314-326, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27481291

RESUMO

UNLABELLED: Recently, meniscus tissue engineering offers a promising management for meniscus regeneration. Although rarely reported, the microarchitectures of scaffolds can deeply influence the behaviors of endogenous or exogenous stem/progenitor cells and subsequent tissue formation in meniscus tissue engineering. Herein, a series of three-dimensional (3D) poly(ε-caprolactone) (PCL) scaffolds with three distinct mean pore sizes (i.e., 215, 320, and 515µm) were fabricated via fused deposition modeling. The scaffold with the mean pore size of 215µm significantly improved both the proliferation and extracellular matrix (ECM) production/deposition of mesenchymal stem cells compared to all other groups in vitro. Moreover, scaffolds with mean pore size of 215µm exhibited the greatest tensile and compressive moduli in all the acellular and cellular studies. In addition, the relatively better results of fibrocartilaginous tissue formation and chondroprotection were observed in the 215µm scaffold group after substituting the rabbit medial meniscectomy for 12weeks. Overall, the mean pore size of 3D-printed PCL scaffold could affect cell behavior, ECM production, biomechanics, and repair effect significantly. The PCL scaffold with mean pore size of 215µm presented superior results both in vitro and in vivo, which could be an alternative for meniscus tissue engineering. STATEMENT OF SIGNIFICANCE: Meniscus tissue engineering provides a promising strategy for meniscus regeneration. In this regard, the microarchitectures (e.g., mean pore size) of scaffolds remarkably impact the behaviors of cells and subsequent tissue formation, which has been rarely reported. Herein, three three-dimensional poly(ε-caprolactone) scaffolds with different mean pore sizes (i.e., 215, 320, and 515µm) were fabricated via fused deposition modeling. The results suggested that the mean pore size significantly affected the behaviors of endogenous or exogenous stem/progenitor cells and subsequent tissue formation. This study furthers our understanding of the cell-scaffold interaction in meniscus tissue engineering, which provides unique insight into the design of meniscus scaffolds for future clinical application.


Assuntos
Menisco/fisiologia , Regeneração , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Fenômenos Biomecânicos , Cartilagem Articular/patologia , Colágeno Tipo II/metabolismo , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Imuno-Histoquímica , Implantes Experimentais , Células-Tronco Mesenquimais/metabolismo , Porosidade , Coelhos
18.
Stem Cells Dev ; 25(16): 1195-207, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27353075

RESUMO

An increasing number of studies have detected mesenchymal stromal cells (MSCs) and mesenchymal progenitor cells (MPCs) in the peripheral blood (PB). This study aimed to systematically review the possibility of using the PB as a source for chondrogenic progenitors. PubMed, the Web of Science, and Embase were searched for relevant articles. The findings of the studies were reviewed to evaluate the biological characteristics of PB-derived MSCs, chondrogenic MPCs, and their applications in cartilage repair. Thirty-six articles were included in the final analysis, 29 of which indicated that PB is a potential source for chondrogenic progenitor cells. Thirty-two studies reporting in vitro data, including 79.2% (19/24) of studies on PB MSCs and 75% (6/8) of studies on chondrogenic PB MPCs, confirmed the existence of PB MSCs and PB MPCs, respectively; all in vivo investigations showed that using PB as a cell source enhanced cartilage repair. PB MSCs were found in most of the animal studies (12/13), whereas 7 of 11 human studies described the presence of PB MSCs. This systematic review strongly indicates the existence of MSCs in the PB of animals, whereas the presence of MSCs in human PB is less clear. Although the presence of both MSCs and chondrogenic MPCs in the PB, as well as a few favorable outcomes associated with the use of PB-derived progenitors for cartilage repair in vivo, suggests that the PB is a potential alternative source of chondrogenic progenitor cells for cartilage repair, the efficacy of these cells has not been compared to those from other sources, such as bone marrow or adipose tissue in controlled studies.


Assuntos
Condrogênese , Células-Tronco de Sangue Periférico/citologia , Animais , Cartilagem/patologia , Humanos , Cicatrização
19.
Tumour Biol ; 37(6): 8337-47, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26729199

RESUMO

Tumor susceptibility gene 101 (TSG101) and activating transcription factor 2 (ATF2) have been suggested to involve in the reactivation of EBV which has implications in the development and progression of breast cancer. Therefore, the polymorphisms of TSG101 and ATF2 may associate with breast cancer risk and prognosis. A case-control study with 1551 breast cancer cases and 1605 age-matched controls were conducted in Guangzhou, China. We have also successfully followed up 1168 cases until December 31, 2014. The variant allele of TSG101 rs2292179 was associated with a non-significant reduced risk of breast cancer, particularly among women with BMI < 24 (kg/m(2)) (P for interaction <0.05). For ATF2 rs3845744, the variant allele was also associated with a significantly reduced breast cancer risk [odds ratio (OR) (95 % confidence interval (CI)) 0.86 (0.74∼1.00)], and the association occurred among only postmenopausal women [OR (95 % CI) 0.69 (0.54∼0.88)] (P for interaction <0.05). Breast cancer risk was further reduced with the increasing numbers of the variant G alleles of the two polymorphisms (P for trend <0.05). We did not find an overall association of the two loci with breast cancer prognosis, while the hazard ratios of the two loci (AG/GG vs. AA) were significantly higher among postmenopausal women than premenopausal women (P = 0.046, 0.016 for TSG101 rs2292179 and ATF2 rs3845744, respectively). In summary, the variant alleles of TSG101 rs2292179 and ATF2 rs3845744 were associated with a reduced risk of breast cancer, particularly for subjects with BMI <24 (kg/m(2)) and postmenopausal women, respectively. The two SNPs and menopausal status may have a significant interaction on breast cancer progression.


Assuntos
Fator 2 Ativador da Transcrição/genética , Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Variação Genética , Herpesvirus Humano 4/genética , Fatores de Transcrição/genética , Ativação Viral/fisiologia , Adulto , Alelos , Neoplasias da Mama/mortalidade , Estudos de Casos e Controles , China , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Fatores de Risco , Taxa de Sobrevida
20.
BMC Musculoskelet Disord ; 17: 45, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26818255

RESUMO

BACKGROUND: Posterior Cruciate Ligament (PCL) ruptures are common sports injuries. One of the key controversies in PCL reconstruction is whether double-bundle reconstruction provides biomechanical and clinical outcomes superior to single-bundle reconstruction. METHODS: We performed a comprehensive search in multiple databases to evaluate the advantages of single-bundle or double bundle reconstructions in anteroposterior stability, graft tension, rotational stability, and functional outcome. RESULTS: Biomechanical comparisons evaluating anteroposterior stability described either no difference or increased stability in double-bundle reconstructions. Comparing these results is complicated by different graft choices, tensioning techniques, and tunnel positions. Biomechanical studies of graft tension demonstrated conflicting results regarding the optimal reconstruction technique. Seven retrospective clinical studies of single- and double-bundle reconstructions with methodological limitations reported no difference in clinical outcome. CONCLUSIONS: The superiority of single-bundle or double-bundle posterior cruciate ligament reconstruction remains uncertain.


Assuntos
Ligamento Cruzado Posterior/lesões , Ligamento Cruzado Posterior/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
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