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Pesquisa : B01.050.150.900.649.313.992.635.505.700.550.508 [Categoria DeCS]
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  1 / 2035 MEDLINE  
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[PMID]:28829592
[Au] Autor:Beaufils F; Cmiljanovic N; Cmiljanovic V; Bohnacker T; Melone A; Marone R; Jackson E; Zhang X; Sele A; Borsari C; Mestan J; Hebeisen P; Hillmann P; Giese B; Zvelebil M; Fabbro D; Williams RL; Rageot D; Wymann MP
[Ad] Endereço:Department of Biomedicine, University of Basel , Mattenstrasse 28, 4058 Basel, Switzerland.
[Ti] Título:5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology.
[So] Source:J Med Chem;60(17):7524-7538, 2017 Sep 14.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclinical characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations. No off-target interactions were detected for 1 in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1 did not bind tubulin, which was observed for the structurally related 4 (BKM120, buparlisib). Compound 1 is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1 demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound's safety profile, identifies 1 as a clinical candidate with a broad application range in oncology, including treatment of brain tumors or CNS metastasis. Compound 1 is currently in phase II clinical trials for advanced solid tumors and refractory lymphoma.
[Mh] Termos MeSH primário: Aminopiridinas/uso terapêutico
Antineoplásicos/uso terapêutico
Morfolinas/uso terapêutico
Neoplasias/tratamento farmacológico
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Inibidores de Proteínas Quinases/uso terapêutico
Serina-Treonina Quinases TOR/antagonistas & inibidores
[Mh] Termos MeSH secundário: Administração Oral
Aminopiridinas/administração & dosagem
Aminopiridinas/farmacocinética
Animais
Antineoplásicos/administração & dosagem
Antineoplásicos/farmacocinética
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Proliferação Celular/efeitos dos fármacos
Cães
Seres Humanos
Camundongos
Modelos Moleculares
Morfolinas/administração & dosagem
Morfolinas/farmacocinética
Neoplasias/metabolismo
Fosfatidilinositol 3-Quinases/metabolismo
Inibidores de Proteínas Quinases/administração & dosagem
Inibidores de Proteínas Quinases/farmacocinética
Ratos
Ratos Nus
Transdução de Sinais/efeitos dos fármacos
Serina-Treonina Quinases TOR/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminopyridines); 0 (Antineoplastic Agents); 0 (Morpholines); 0 (NVP-BKM120); 0 (Protein Kinase Inhibitors); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.1 (TOR Serine-Threonine Kinases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00930


  2 / 2035 MEDLINE  
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[PMID]:28825600
[Au] Autor:Lu P; Ceto S; Wang Y; Graham L; Wu D; Kumamaru H; Staufenberg E; Tuszynski MH
[Ad] Endereço:VA San Diego Healthcare System, San Diego, California, USA.
[Ti] Título:Prolonged human neural stem cell maturation supports recovery in injured rodent CNS.
[So] Source:J Clin Invest;127(9):3287-3299, 2017 Sep 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neural stem cells (NSCs) differentiate into both neurons and glia, and strategies using human NSCs have the potential to restore function following spinal cord injury (SCI). However, the time period of maturation for human NSCs in adult injured CNS is not well defined, posing fundamental questions about the design and implementation of NSC-based therapies. This work assessed human H9 NSCs that were implanted into sites of SCI in immunodeficient rats over a period of 1.5 years. Notably, grafts showed evidence of continued maturation over the entire assessment period. Markers of neuronal maturity were first expressed 3 months after grafting. However, neurogenesis, neuronal pruning, and neuronal enlargement continued over the next year, while total graft size remained stable over time. Axons emerged early from grafts in very high numbers, and half of these projections persisted by 1.5 years. Mature astrocyte markers first appeared after 6 months, while more mature oligodendrocyte markers were not present until 1 year after grafting. Astrocytes slowly migrated from grafts. Notably, functional recovery began more than 1 year after grafting. Thus, human NSCs retain an intrinsic human rate of maturation, despite implantation into the injured rodent spinal cord, yet they support delayed functional recovery, a finding of great importance in planning human clinical trials.
[Mh] Termos MeSH primário: Sistema Nervoso Central/lesões
Células-Tronco Neurais/citologia
Transplante de Células-Tronco
[Mh] Termos MeSH secundário: Animais
Astrócitos/citologia
Axônios/metabolismo
Diferenciação Celular
Linhagem Celular
Movimento Celular
Células-Tronco Embrionárias/citologia
Feminino
Seres Humanos
Neurogênese
Neuroglia/metabolismo
Neurônios/metabolismo
Oligodendroglia/citologia
Ratos
Ratos Nus
Recuperação de Função Fisiológica
Medula Espinal/fisiopatologia
Traumatismos da Medula Espinal/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE


  3 / 2035 MEDLINE  
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[PMID]:28697500
[Au] Autor:Zhang YD; Zhao SC; Zhu ZS; Wang YF; Liu JX; Zhang ZC; Xue F
[Ad] Endereço:Department of Orthopaedics, Shanghai Fengxian Central Hospital, South Campus of Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
[Ti] Título:Cx43- and Smad-Mediated TGF-ß/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation.
[So] Source:Cell Physiol Biochem;42(4):1277-1293, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-ß/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. METHODS: BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes. The condition of cartilage and ossification were measured by a series of staining methods. Subcutaneous injection of mesenchymal stem cells (MSCs) into nude rats was performed. RESULTS: After transfection, compared to the AdGFP group, the corresponding target mRNAs were overexpressed in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups, and overexpression of BMP2 at the mRNA and protein expression was observed in the AdSmad1 and AdCx43 + AdSmad1 groups. The mRNA expressions of aggrecan (ACAN) and collagen type II alpha 1 (Col2a1), the glycosaminoglycan content of the extracellular matrix and the expression of type II collagen, Col2a1, osteopontin (OPN) and osteocalcin (OC) were higher in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups than in the AdGFP group; alkaline phosphatase (ALP) activity and mRNA and protein expressions of Runx2 were also higher in these groups than in the AdGFP group. Heterotopic osteogenesis tests demonstrated evident cartilage differentiation ability in the AdCx43 + AdSmad1 + AdBMP2 groups. In comparison, the AdCx43 + AdSmad1 and AdSmad1 groups exhibited weaker cartilage differentiation abilities. CONCLUSION: Cx43 and Smad1 promote BMP-induced cartilage differentiation of BMSCs and inhibit osteoblast differentiation, which provide a new strategy for cartilage tissue engineering using exogenous Cx43 and Smad1.
[Mh] Termos MeSH primário: Proteína Morfogenética Óssea 2/genética
Condrócitos/metabolismo
Condrogênese/genética
Conexina 43/genética
Células Mesenquimais Estromais/metabolismo
Proteína Smad1/genética
Fator de Crescimento Transformador beta/genética
[Mh] Termos MeSH secundário: Adenoviridae/genética
Adenoviridae/metabolismo
Agrecanas/genética
Agrecanas/metabolismo
Animais
Células da Medula Óssea/citologia
Células da Medula Óssea/metabolismo
Proteína Morfogenética Óssea 2/metabolismo
Cartilagem/citologia
Cartilagem/metabolismo
Diferenciação Celular
Condrócitos/citologia
Colágeno Tipo II/genética
Colágeno Tipo II/metabolismo
Conexina 43/metabolismo
Subunidade alfa 1 de Fator de Ligação ao Core/genética
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo
Regulação da Expressão Gênica
Vetores Genéticos/química
Vetores Genéticos/metabolismo
Injeções Subcutâneas
Transplante de Células-Tronco Mesenquimais
Células Mesenquimais Estromais/citologia
Osteocalcina/genética
Osteocalcina/metabolismo
Osteogênese/genética
Osteopontina/genética
Osteopontina/metabolismo
Cultura Primária de Células
Ratos
Ratos Nus
Ratos Wistar
Transdução de Sinais
Proteína Smad1/metabolismo
Transfecção
Fator de Crescimento Transformador beta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aggrecans); 0 (Bmp2 protein, rat); 0 (Bone Morphogenetic Protein 2); 0 (COL2A1 protein, rat); 0 (Collagen Type II); 0 (Connexin 43); 0 (Core Binding Factor Alpha 1 Subunit); 0 (Runx2 protein, rat); 0 (Smad1 Protein); 0 (Smad1 protein, rat); 0 (Spp1 protein, rat); 0 (Transforming Growth Factor beta); 0 (connexin 43 protein, rat); 104982-03-8 (Osteocalcin); 106441-73-0 (Osteopontin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170712
[St] Status:MEDLINE
[do] DOI:10.1159/000478957


  4 / 2035 MEDLINE  
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[PMID]:28604083
[Au] Autor:Ikeda M; Imaizumi M; Yoshie S; Nakamura R; Otsuki K; Murono S; Omori K
[Ad] Endereço:1 Department of Otolaryngology, Fukushima Medical University, Fukushima, Japan.
[Ti] Título:Implantation of Induced Pluripotent Stem Cell-Derived Tracheal Epithelial Cells.
[So] Source:Ann Otol Rhinol Laryngol;126(7):517-524, 2017 Jul.
[Is] ISSN:1943-572X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Compared with using autologous tissue, the use of artificial materials in the regeneration of tracheal defects is minimally invasive. However, this technique requires early epithelialization on the inner side of the artificial trachea. After differentiation from induced pluripotent stem cells (iPSCs), tracheal epithelial tissues may be used to produce artificial tracheas. Herein, we aimed to demonstrate that after differentiation from fluorescent protein-labeled iPSCs, tracheal epithelial tissues survived in nude rats with tracheal defects. METHODS: Red fluorescent tdTomato protein was electroporated into mouse iPSCs to produce tdTomato-labeled iPSCs. Embryoid bodies derived from these iPSCs were then cultured in differentiation medium supplemented with growth factors, followed by culture on air-liquid interfaces for further differentiation into tracheal epithelium. The cells were implanted with artificial tracheas into nude rats with tracheal defects on day 26 of cultivation. On day 7 after implantation, the tracheas were exposed and examined histologically. RESULTS: Tracheal epithelial tissue derived from tdTomato-labeled iPSCs survived in the tracheal defects. Moreover, immunochemical analyses showed that differentiated tissues had epithelial structures similar to those of proximal tracheal tissues. CONCLUSIONS: After differentiation from iPSCs, tracheal epithelial tissues survived in rat bodies, warranting the use of iPSCs for epithelial regeneration in tracheal defects.
[Mh] Termos MeSH primário: Células Epiteliais/fisiologia
Células-Tronco Pluripotentes Induzidas/fisiologia
Engenharia Tecidual/métodos
Traqueia/citologia
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular
Células Cultivadas
Corpos Embrioides/fisiologia
Corantes Fluorescentes
Proteínas Luminescentes
Masculino
Ratos Nus
Regeneração
Tecidos Suporte
Traqueia/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorescent Dyes); 0 (Luminescent Proteins); 0 (red fluorescent protein)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1177/0003489417713504


  5 / 2035 MEDLINE  
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[PMID]:28365701
[Au] Autor:Wei GJ; An G; Shi ZW; Wang KF; Guan Y; Wang YS; Han B; Yu EM; Li PF; Dong DM; Wang LP; Teng ZW; Zhao DL
[Ad] Endereço:Department of Orthopaedics, the 1st Affiliated Hospital of Harbin Medical University, Harbin, China.
[Ti] Título:Suppression of MicroRNA-383 Enhances Therapeutic Potential of Human Bone-Marrow-Derived Mesenchymal Stem Cells in Treating Spinal Cord Injury via GDNF.
[So] Source:Cell Physiol Biochem;41(4):1435-1444, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) has been used to treat spinal cord injury (SCI) to enhance tissue repair and neural cell regeneration. Glial cell line derived neurotrophic factor (GDNF) is an identified neural growth and survival factor. Here, we examined whether modification of GDNF levels in MSCs may further increase the potential of MSCs in promoting neural cell regeneration and subsequently the therapeutic outcome. METHODS: We examined the mRNA and protein levels of GDNF in human MSCs by RT-qPCR and Western blot, respectively. Bioinformatics analyses were done to predict microRNAs (miRNAs) that target GDNF in MSCs. The functional binding of miRNAs to GDNF mRNA was examined by a dual luciferase reporter assay. MSCs were transduced with adeno-associated virus (AAV) carrying null or antisense for miR-383 (as-miR-383), which were transplanted into nude rats that underwent SCI. The intact tissue, cavity volume, and recovery of locomotor activity were assessed. RESULTS: MSCs expressed very low GDNF protein, but surprisingly high levels of GDNF mRNA. Bioinformatics analyses showed that miR-383 inhibited protein translation of GDNF, through binding to the 3'-UTR of the GDNF mRNA. MSCs transduced with AAV-as-miR-383 further increased the intact tissue percentage, decreased cavity volume, and enhanced the recovery of locomotor activity in nude rats that underwent SCI, compared to MSCs. CONCLUSIONS: Suppression of miR-383 may increase the therapeutic potential of human bone-marrow-derived MSCs in treating SCI via augmentation of GDNF protein levels.
[Mh] Termos MeSH primário: Células da Medula Óssea/metabolismo
Fator Neurotrófico Derivado de Linhagem de Célula Glial/biossíntese
Transplante de Células-Tronco Mesenquimais
Células Mesenquimais Estromais/metabolismo
MicroRNAs/biossíntese
Traumatismos da Medula Espinal
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Adulto
Animais
Modelos Animais de Doenças
Células HEK293
Xenoenxertos
Seres Humanos
Masculino
Ratos
Ratos Nus
Traumatismos da Medula Espinal/metabolismo
Traumatismos da Medula Espinal/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (GDNF protein, human); 0 (Glial Cell Line-Derived Neurotrophic Factor); 0 (MIRN383 microRNA, human); 0 (MicroRNAs)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170403
[St] Status:MEDLINE
[do] DOI:10.1159/000468057


  6 / 2035 MEDLINE  
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[PMID]:28290232
[Au] Autor:Imaizumi M; Li-Jessen NY; Sato Y; Yang DT; Thibeault SL
[Ad] Endereço:1 Department of Otolaryngology, School of Medicine, Fukushima Medical University, Fukushima City, Japan.
[Ti] Título:Retention of Human-Induced Pluripotent Stem Cells (hiPS) With Injectable HA Hydrogels for Vocal Fold Engineering.
[So] Source:Ann Otol Rhinol Laryngol;126(4):304-314, 2017 Apr.
[Is] ISSN:1943-572X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds. METHODS: Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH). RESULTS: Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only. CONCLUSIONS: Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.
[Mh] Termos MeSH primário: Fator de Crescimento Epidérmico/farmacologia
Regeneração Tecidual Guiada/métodos
Ácido Hialurônico/farmacologia
Hidrogéis/farmacologia
Células-Tronco Pluripotentes Induzidas/transplante
Engenharia Tecidual/métodos
Tecidos Suporte
Prega Vocal/lesões
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Imuno-Histoquímica
Hibridização in Situ Fluorescente
Ratos
Ratos Nus
Prega Vocal/efeitos dos fármacos
Prega Vocal/metabolismo
Prega Vocal/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydrogels); 62229-50-9 (Epidermal Growth Factor); 9004-61-9 (Hyaluronic Acid)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170417
[Lr] Data última revisão:
170417
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1177/0003489417691296


  7 / 2035 MEDLINE  
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[PMID]:28282242
[Au] Autor:Inokuchi T; Matsumoto T; Takayama K; Nakano N; Zhang S; Araki D; Matsushita T; Kuroda R
[Ad] Endereço:Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
[Ti] Título:Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament-Derived Cells.
[So] Source:Am J Sports Med;45(6):1359-1369, 2017 May.
[Is] ISSN:1552-3365
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Vascular CD34+ cells in anterior cruciate ligament (ACL) tissue have the potential for high proliferation and multilineage differentiation that can accelerate tendon-bone healing. While patient characteristics, such as age, can affect tendon-bone healing, the influence of elapsed time after injury on the healing process is unclear. HYPOTHESIS: Cells obtained during the early phase after injury will exhibit a greater tendon-bone healing potential compared with chronic phase counterparts when applied to an immunodeficient rat model of ACL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Adult human ACL-ruptured tissue was harvested from patients undergoing arthroscopic primary ACL reconstruction and classified into 2 groups based on the time elapsed between injury and surgery: (1) early group (≤3 months from injury) and (2) chronic group (>3 months from injury). In addition, 76 ten-week-old female immunodeficient rats underwent ACL reconstruction, followed by intracapsular administration of one of the following: (1) ACL-derived cells from the early group (n = 5), (2) ACL-derived cells from the chronic group (n = 5), or (3) phosphate-buffered saline (PBS) only (n = 5). During the 8 weeks after surgery, histological (weeks 2, 4, 8), immunohistochemical (week 2), radiographic (weeks 0, 2, 4, 8), and biomechanical (week 8) analyses were performed to evaluate tendon-bone healing. RESULTS: In the early group, the histological evaluation showed early healing, induction of endochondral ossification-like integration, and mature bone ingrowth. Micro-computed tomography showed that the tibial bone tunnels at week 4 and week 8 were significantly reduced in the early group compared with those in the chronic group and PBS group ( P < .05). Moreover, biomechanical tensile strength was significantly greater in the early group than in the other groups ( P < .05). An accelerated healing potential in the early group was further demonstrated by the enhancement of intrinsic angiogenesis/osteogenesis and human-derived vasculogenesis/osteogenesis. CONCLUSION: Compared with human ACL-derived cells obtained during the chronic phase, cells obtained during the early phase after injury have a greater tendon-bone healing potential when used in an immunodeficient rat model of ACL reconstruction. CLINICAL RELEVANCE: During ACL reconstruction surgery, transplanting ACL remnant tissue in the early phase after injury could accelerate and enhance tendon-bone healing.
[Mh] Termos MeSH primário: Reconstrução do Ligamento Cruzado Anterior/métodos
Ligamento Cruzado Anterior/citologia
Cicatrização/fisiologia
[Mh] Termos MeSH secundário: Adulto
Animais
Ligamento Cruzado Anterior/cirurgia
Diferenciação Celular
Proliferação Celular
Feminino
Seres Humanos
Osteogênese
Ratos Nus
Tendões/transplante
Resistência à Tração
Tíbia/diagnóstico por imagem
Tíbia/fisiologia
Tíbia/cirurgia
Fatores de Tempo
Microtomografia por Raio-X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1177/0363546517689871


  8 / 2035 MEDLINE  
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[PMID]:28261617
[Au] Autor:Liu S; Jia Y; Yuan M; Guo W; Huang J; Zhao B; Peng J; Xu W; Lu S; Guo Q
[Ad] Endereço:Beijing Key Laboratory of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Institute of Orthopaedics, Chinese PLA General Hospital, Beijing 100853, China.
[Ti] Título:Repair of Osteochondral Defects Using Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells in a Rabbit Model.
[So] Source:Biomed Res Int;2017:8760383, 2017.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Umbilical cord Wharton's jelly-derived mesenchymal stem cell (WJMSC) is a new-found mesenchymal stem cell in recent years with multiple lineage potential. Due to its abundant resources, no damage procurement, and lower immunogenicity than other adult MSCs, WJMSC promises to be a good xenogenous cell candidate for tissue engineering. This in vivo pilot study explored the use of human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs) containing a tissue engineering construct xenotransplant in rabbits to repair full-thickness cartilage defects in the femoral patellar groove. We observed orderly spatial-temporal remodeling of hWJMSCs into cartilage tissues during repair over 16 months, with characteristic architectural features, including a hyaline-like neocartilage layer with good surface regularity, complete integration with adjacent host cartilage, and regenerated subchondral bone. No immune rejection was detected when xenograft hWJMSCs were implanted into rabbit cartilage defects. The repair results using hWJMSCs were superior to those of chondrogenically induced hWJMSCs after assessing gross appearance and histological grading scores. These preliminary results suggest that using novel undifferentiated hWJMSCs as seed cells might be a better approach than using transforming growth factor- -induced differentiated hWJMSCs for in vivo tissue engineering treatment of cartilage defects. hWJMSC allografts may be promising for clinical applications.
[Mh] Termos MeSH primário: Condrogênese
Transplante de Células-Tronco Mesenquimais
Células Mesenquimais Estromais/citologia
Cordão Umbilical/citologia
Geleia de Wharton/citologia
[Mh] Termos MeSH secundário: Aloenxertos
Animais
Cartilagem/lesões
Cartilagem/patologia
Técnicas de Cultura de Células
Diferenciação Celular
Sobrevivência Celular
Modelos Animais de Doenças
Seres Humanos
Sistema Imunitário
Masculino
Microscopia Eletrônica de Varredura
Coelhos
Ratos
Ratos Nus
Engenharia Tecidual/métodos
Cicatrização
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170404
[Lr] Data última revisão:
170404
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE
[do] DOI:10.1155/2017/8760383


  9 / 2035 MEDLINE  
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[PMID]:28255341
[Au] Autor:Toussaint M; Pinel S; Auger F; Durieux N; Thomassin M; Thomas E; Moussaron A; Meng D; Plénat F; Amouroux M; Bastogne T; Frochot C; Tillement O; Lux F; Barberi-Heyob M
[Ad] Endereço:CRAN UMR 7039, CNRS, VandÅ“uvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, VandÅ“uvre-lès-Nancy, France.
[Ti] Título:Proton MR Spectroscopy and Diffusion MR Imaging Monitoring to Predict Tumor Response to Interstitial Photodynamic Therapy for Glioblastoma.
[So] Source:Theranostics;7(2):436-451, 2017.
[Is] ISSN:1838-7640
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:Despite recent progress in conventional therapeutic approaches, the vast majority of glioblastoma recur locally, indicating that a more aggressive local therapy is required. Interstitial photodynamic therapy (iPDT) appears as a very promising and complementary approach to conventional therapies. However, an optimal fractionation scheme for iPDT remains the indispensable requirement. To achieve that major goal, we suggested following iPDT tumor response by a non-invasive imaging monitoring. Nude rats bearing intracranial glioblastoma U87MG xenografts were treated by iPDT, just after intravenous injection of AGuIX® nanoparticles, encapsulating PDT and imaging agents. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) allowed us an original longitudinal follow-up of post-treatment effects to discriminate early predictive markers. We successfully used conventional MRI, T2 star (T2*), Diffusion Weighted Imaging (DWI) and MRS to extract relevant profiles on tissue cytoarchitectural alterations, local vascular disruption and metabolic information on brain tumor biology, achieving earlier assessment of tumor response. From one day post-iPDT, DWI and MRS allowed us to identify promising markers such as the Apparent Diffusion Coefficient (ADC) values, lipids, choline and myoInositol levels that led us to distinguish iPDT responders from non-responders. All these responses give us warning signs well before the tumor escapes and that the growth would be appreciated.
[Mh] Termos MeSH primário: Monitoramento de Medicamentos/métodos
Glioblastoma/diagnóstico
Glioblastoma/terapia
Imagem por Ressonância Magnética
Espectroscopia de Ressonância Magnética/métodos
Fotoquimioterapia
Prótons
[Mh] Termos MeSH secundário: Animais
Meios de Contraste/administração & dosagem
Modelos Animais de Doenças
Xenoenxertos
Estudos Longitudinais
Nanopartículas/administração & dosagem
Fármacos Fotossensibilizantes/administração & dosagem
Ratos Nus
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contrast Media); 0 (Photosensitizing Agents); 0 (Protons)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.7150/thno.17218


  10 / 2035 MEDLINE  
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[PMID]:28236065
[Au] Autor:Zhou Z; Luther N; Singh R; Boockvar JA; Souweidane MM; Greenfield JP
[Ad] Endereço:Department of Neurological Surgery, Weill Medical College of Cornell University, 525 East 68th Street, Box 99, New York, NY, 10065, USA. zhipingzhou@gmail.com.
[Ti] Título:Glioblastoma spheroids produce infiltrative gliomas in the rat brainstem.
[So] Source:Childs Nerv Syst;33(3):437-446, 2017 Mar.
[Is] ISSN:1433-0350
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is universally fatal without proven therapy other than radiation therapy for palliation. Representative animal models will play an essential role in the preclinical stage of future therapy development. To address the shortage of representative models, we created a novel infiltrative brainstem glioma model in rats based on glioblastoma spheroids. METHODS: Cells dissociated from glioblastoma spheroids grown from surgical specimens were implanted into the brainstem of NIH nude rats. Animals were serially assessed clinically and radiographically with magnetic resonance imaging (MRI). Tumors were further characterized using histology, immunohistochemistry, and cytogenetics. RESULTS: Tumor generation was successful in all animals receiving glioblastoma spheroid cells. The rats survived 17-25 weeks before severe symptoms developed. The tumors showed as diffuse hyperintense lesions on T2-weighted images. Histologically, they demonstrated cellular heterogeneity, and infiltrative and invasive features, with cells engorging vascular structures. The tumors were shown to comprise immature human origin glial tumor cells, with human epidermal growth factor receptor (EGFR) gene amplification and gain. CONCLUSIONS: This study showed that cells from glioblastoma spheroids produced infiltrative gliomas in rat brainstem. The rat brainstem gliomas are radiographically and histologically accurate compared to DIPG. These tumors develop over several months that would allow sequential clinical and radiographic assessments of therapeutic interventions. This study demonstrated in principle the feasibility of developing patient-specific animal models based on putative cancer stem cells from biopsy or resection samples.
[Mh] Termos MeSH primário: Neoplasias do Tronco Encefálico/patologia
Regulação Neoplásica da Expressão Gênica/fisiologia
Glioblastoma/patologia
Infiltração de Neutrófilos/fisiologia
[Mh] Termos MeSH secundário: Animais
Neoplasias do Tronco Encefálico/diagnóstico por imagem
Modelos Animais de Doenças
Proteína Glial Fibrilar Ácida/metabolismo
Glioblastoma/diagnóstico por imagem
Seres Humanos
Isoantígenos/genética
Isoantígenos/metabolismo
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Transplante de Neoplasias
Ratos
Ratos Nus
Receptor do Fator de Crescimento Epidérmico/genética
Receptor do Fator de Crescimento Epidérmico/metabolismo
Esferoides Celulares
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glial Fibrillary Acidic Protein); 0 (Isoantigens); 0 (neutrophil-specific antigen SH); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE
[do] DOI:10.1007/s00381-017-3344-y



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