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1.
Am J Sports Med ; 43(2): 399-406, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25492035

RESUMO

BACKGROUND: Recently, mesenchymal stem cells (MSCs) have been suggested as a source for cell-based treatment of cartilage lesions based on the ability of these cells to differentiate into chondrocytes. PURPOSE: To characterize MSCs derived from the synovial fluid in ankle joints with osteochondral lesion of the talus (OLT). STUDY DESIGN: Controlled laboratory study. METHODS: Synovial fluid was collected from the ankle joints of 28 patients with OLT who underwent arthroscopic marrow stimulation between September 2011 and April 2012. Epitope profiles and multilineage differentiation were assessed to characterize the synovial fluid MSCs. To clarify the origin of synovial fluid MSCs, we assessed gene profiles of MSCs derived from various mesenchymal tissues by reverse transcription-polymerase chain reaction (RT-PCR) analysis. RESULTS: Synovial fluid MSCs expressed CD90 and CD105, showed low expression of CD14 and CD34, and underwent multilineage differentiation in vitro. The RT-PCR revealed strong expression of CD90, CD44, and CD73, whereas CD45 and CD133 were not detected. The colony number of synovial fluid MSCs from OLT significantly increased in stages C and D, as defined by arthroscopic classification. Gene expression profiles indicated that synovial fluid MSCs derived from the patients with OLT were more similar to MSCs from synovium than to MSCs from bone marrow and adipose tissue. CONCLUSION: This study confirmed that human synovial fluid is a good source of MSCs, with the capacity to differentiate toward several cell lineages. Further study with matched controls of synovial fluid MSCs derived from ankle joints without OLT is required for a more accurate evaluation of synovial fluid MSCs. CLINICAL RELEVANCE: The findings of this study provide a platform for exploring the potential role of synovial fluid MSCs in OLT and their therapeutic potential in novel joint regeneration strategies.


Assuntos
Articulação do Tornozelo/patologia , Antígenos CD/genética , Cartilagem Articular/patologia , Células-Tronco Mesenquimais/citologia , Líquido Sinovial/citologia , Tálus/patologia , Transcriptoma , Tecido Adiposo/citologia , Adulto , Células da Medula Óssea , Proteínas de Ligação ao Cálcio/genética , Diferenciação Celular , Condrócitos/citologia , Ensaio de Unidades Formadoras de Colônias , Proteínas da Matriz Extracelular/genética , Feminino , Glicoproteínas/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/metabolismo , Membrana Sinovial/citologia , Proteínas Supressoras de Tumor , Adulto Jovem
2.
Knee Surg Sports Traumatol Arthrosc ; 23(5): 1308-16, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24326779

RESUMO

PURPOSE: In the present study, the clinical outcomes and second-look arthroscopic findings of intra-articular injection of stem cells with arthroscopic lavage for treatment of elderly patients with knee osteoarthritis (OA) were evaluated. METHODS: Stem cell injections combined with arthroscopic lavage were administered to 30 elderly patients (≥65 years) with knee OA. Subcutaneous adipose tissue was harvested from both buttocks by liposuction. After stromal vascular fractions were isolated, a mean of 4.04 × 10(6) stem cells (9.7 % of 4.16 × 10(7) stromal vascular fraction cells) were prepared and injected in the selected knees of patients after arthroscopic lavage. Outcome measures included the Knee Injury and Osteoarthritis Outcome Scores, visual analog scale, and Lysholm score at preoperative and 3-, 12-, and 2-year follow-up visits. Sixteen patients underwent second-look arthroscopy. RESULTS: Almost all patients showed significant improvement in all clinical outcomes at the final follow-up examination. All clinical results significantly improved at 2-year follow-up compared to 12-month follow-up (P < 0.05). Among elderly patients aged >65 years, only five patients demonstrated worsening of Kellgren-Lawrence grade. On second-look arthroscopy, 87.5 % of elderly patients (14/16) improved or maintained cartilage status at least 2 years postoperatively. Moreover, none of the patients underwent total knee arthroplasty during this 2-year period. CONCLUSION: Adipose-derived stem cell therapy for elderly patients with knee OA was effective in cartilage healing, reducing pain, and improving function. Therefore, adipose-derived stem cell treatment appears to be a good option for OA treatment in elderly patients. LEVEL OF EVIDENCE: Therapeutic case series study, Level IV.


Assuntos
Artroplastia do Joelho , Artroscopia/métodos , Articulação do Joelho/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite do Joelho/cirurgia , Cirurgia de Second-Look/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cartilagem/transplante , Feminino , Seguimentos , Humanos , Injeções Intra-Articulares , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/fisiopatologia , Amplitude de Movimento Articular , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento
3.
Biochem Biophys Res Commun ; 450(4): 1593-9, 2014 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-25035928

RESUMO

Transforming growth factor-beta (TGF-ß) superfamily proteins play a critical role in proliferation, differentiation, and other functions of mesenchymal stem cells (MSCs). During chondrogenic differentiation of MSCs, TGF-ß up-regulates chondrogenic gene expression by enhancing the expression of the transcription factor SRY (sex-determining region Y)-box9 (Sox9). In this study, we investigated the effect of continuous TGF-ß1 overexpression in human synovium-derived MSCs (hSD-MSCs) on immunophenotype, differentiation potential, and proliferation rate. hSD-MSCs were transduced with recombinant retroviruses (rRV) encoding TGF-ß1. The results revealed that continuous overexpression of TGF-ß1 did not affect their phenotype as evidenced by flow cytometry and reverse transcriptase PCR (RT-PCR). In addition, continuous TGF-ß1 overexpression strongly enhanced cell proliferation of hSD-MSCs compared to the control groups. Also, induction of chondrogenesis was more effective in rRV-TGFB-transduced hSD-MSCs as shown by RT-PCR for chondrogenic markers, toluidine blue staining and glycosaminoglycan (GAG)/DNA ratio. Our data suggest that overexpression of TGF-ß1 positively enhances the proliferation and chondrogenic potential of hSD-MSCs.


Assuntos
Cartilagem/citologia , Diferenciação Celular , Proliferação de Células , Células-Tronco/citologia , Membrana Sinovial/citologia , Fator de Crescimento Transformador beta1/metabolismo , Células Cultivadas , Citometria de Fluxo , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução Genética
4.
Biochem Biophys Res Commun ; 447(4): 715-20, 2014 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-24769201

RESUMO

Rheumatoid arthritis (RA) and osteoarthritis (OA) are primarily chronic inflammatory diseases. Mesenchymal stem cells (MSCs) have the ability to differentiate into cells of the mesodermal lineage, and to regulate immunomodulatory activity. Specifically, MSCs have been shown to secrete insulin-like growth factor 1 (IGF-1). The purpose of the present study was to examine the inhibitory effects on inflammatory activity from a co-culture of human synovium-derived mesenchymal stem cells (hSDMSCs) and sodium nitroprusside (SNP)-stimulated chondrocytes. First, chondrocytes were treated with SNP to generate an in vitro model of RA or OA. Next, the co-culture of hSDMSCs with SNP-stimulated chondrocytes reduced inflammatory cytokine secretion, inhibited expression of inflammation activity-related genes, generated IGF-1 secretion, and increased the chondrocyte proliferation rate. To evaluate the effect of IGF-1 on inhibition of inflammation, chondrocytes pre-treated with IGF-1 were treated with SNP, and then the production of inflammatory cytokines was analyzed. Treatment with IGF-1 was shown to significantly reduce inflammatory cytokine secretion in SNP-stimulated chondrocytes. Our results suggest that hSDMSCs offer a new strategy to promote cell-based cartilage regeneration in RA or OA.


Assuntos
Condrócitos/citologia , Condrócitos/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Artrite Reumatoide/terapia , Cartilagem/metabolismo , Cartilagem/patologia , Proliferação de Células , Condrócitos/efeitos dos fármacos , Técnicas de Cocultura , Citocinas/biossíntese , Citocinas/genética , Expressão Gênica , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Mediadores da Inflamação/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Modelos Biológicos , Nitroprussiato/farmacologia , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoartrite/terapia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regeneração , Membrana Sinovial/citologia , Membrana Sinovial/metabolismo
5.
J Orthop Res ; 32(4): 551-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24338609

RESUMO

The purpose of this study was to investigate the anti-inflammatory effect of platelet-rich plasma (PRP) with collagen matrix on human nucleus pulposus (NP) cell in response to pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). NP cells from human disks were cultured in a monolayer and maintained in the collagen matrix prior to the addition of recombinant human IL-1 and TNF-α. After applying IL-1 and TNF-α, PRP prepared by using a commercially available platelet concentration system was added. The response was investigated using real-time PCR for mRNA expression of type II collagen, aggrecan, matrix metalloproteinase-3 (MMP-3), and cyclooxygenase-2 (COX-2). The combination of IL-1ß and TNF-α led to decrease of matrix synthesis gene expression such as collagen type II and aggrecan and increase of the degradation gene expression of COX-2 and MMP-3, compared to the control. Consecutive PRP exposure significantly recovered the down-regulated gene expression of collagen type II and aggrecan and significantly reduced the increased MMP-3 and COX-2 gene expression, compared to that of control groups with pro-inflammatory cytokines. The administration of PRP with collagen matrix markedly suppressed cytokine-induced pro-inflammatory degrading enzymes and mediators in the NP cell. It also rescued gene expression concerning matrix synthesis, thereby stabilizing NP cell differentiation.


Assuntos
Interleucina-1beta/fisiologia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/terapia , Plasma Rico em Plaquetas , Fator de Necrose Tumoral alfa/fisiologia , Colágeno Tipo II/antagonistas & inibidores , Colágeno Tipo II/biossíntese , Ciclo-Oxigenase 2/biossíntese , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/fisiologia , Voluntários Saudáveis , Humanos , Degeneração do Disco Intervertebral/patologia , Metaloproteinase 3 da Matriz/biossíntese , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Plasma Rico em Plaquetas/química , Plasma Rico em Plaquetas/citologia
6.
J Biomed Biotechnol ; 2012: 956345, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23251085

RESUMO

Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient's conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering.


Assuntos
Prótese Vascular/tendências , Engenharia Tecidual/tendências , Animais , Vasos Sanguíneos/anatomia & histologia , Vasos Sanguíneos/fisiologia , Sistema Cardiovascular , História do Século XX , Humanos , Engenharia Tecidual/história , Alicerces Teciduais
7.
Cell Physiol Biochem ; 21(1-3): 225-38, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18209489

RESUMO

The primary objective of this study was to determine the possible apoptotic cell death preventive effects of the antioxidant selenium using an experimental rat spinal cord injury (SCI) model and cultured spinal cord-derived neural progenitor cells (NPCs). Sodium selenite treatment exerted a profound preventive effect on apoptotic cell death, including p-P38, p-SAPK/JNK, caspases, and PARP activity, and ameliorated astrogliosis and hypomyelination, which occurs in regions of active cell death in the spinal cords of SCI rats. The foremost protective effect of selenite in SCI would therefore be manifested in the suppression of acute secondary apoptotic cell death. However, selenite does not appear to exert an anti-inflammatory function associated with active microglia and macrophage propagation or infiltration into the lesion site. Selenite-mediated neuroprotection has been linked to selenite's attenuation or inhibition of p38 mitogen-activated protein kinase, pSAPK/JNK, and Bax activation in in vitro and in vivo SCI lesion sites. Selenite also attenuated cell death via the prevention of cytochrome c release, caspase activation, and ROS accumulation in the cytosol. Also, our study showed that selenite administered immediately after SCI significantly diminishes functional deficits. The selenite-treated group recovered hind limb reflexes more rapidly, and a higher percentage of these rats regained responses to a greater degree than was seen in the untreated injured rats. Our data indicate that the therapeutic outcome of selenite is most likely the consequence of its comprehensive apoptotic cell death blocking effects, resulting in the protection of white matter, oligodendrocytes, and neurons, and the inhibition of astrogliosis. The finding that the administration of selenite prevents secondary pathological events in traumatic spinal cord injuries, and promotes the recovery of motor function in an animal model. Its efficacy may facilitate the development of novel drug targets for the treatment of SCI.


Assuntos
Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Espécies Reativas de Oxigênio/metabolismo , Selênio/farmacologia , Traumatismos da Medula Espinal/patologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citoproteção/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Microglia/patologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Selenito de Sódio/farmacologia , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/enzimologia , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Biochim Biophys Acta ; 1772(11-12): 1199-210, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17997286

RESUMO

This study was designed to investigate possible prevention of apoptotic cell death by selenium, an antioxidant, using cultured brain-derived neural progenitor cells (NPCs) and an experimental mouse brain trauma (BT) model. We tested some of the neuroprotective effects of sodium selenite in NPC cells by monitoring thioredoxin reductase (TR) expression, optimum H(2)O(2) removal, and consequent inhibition of pro-apoptotic events including cytochrome c release and caspase 3 and 9 activation. Analysis of key apoptotic regulators during H(2)O(2)-induced apoptosis of NPCs showed that selenite blocks the activation of c-jun N-terminal protein kinase (JNK)/P38 mitogen-activated protein kinase (MAPK), and Akt survival protein. Moreover, selenite activates p44/42 MAPK and inhibits the downregulation of Bcl2 in selenite-treated NPC cells. For in vivo experiments, the effects of selenite on H(2)O(2) neurotoxicity were tested using several biochemical and morphologic markers. Here we show that selenite potentially inhibits H(2)O(2)-induced apoptosis of NPCs and in traumatic brain injury. This in vivo protective function was also associated with inhibition of H(2)O(2)-induced reactive oxygen species (ROS) generation, cytochrome c release and caspase 3 and 9 activation. Our data show that the protective function of selenite through attenuation of secondary pathological events most likely results from its comprehensive effects that block apoptotic cell death, resulting in the maintenance of functional neurons and in inhibition of astrogliosis. The finding that selenite administration prevents secondary pathological events in an animal model of traumatic brain injury, as well as its efficacy, may provide novel drug targets for treating brain trauma.


Assuntos
Apoptose/efeitos dos fármacos , Lesões Encefálicas/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Espécies Reativas de Oxigênio/metabolismo , Selênio/farmacologia , Células-Tronco/patologia , Animais , Lesões Encefálicas/enzimologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Camundongos , Microglia/efeitos dos fármacos , Microglia/patologia , Neurônios/enzimologia , Neurônios/metabolismo , Selenito de Sódio/farmacologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/enzimologia , Células-Tronco/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Brain Pathol ; 17(3): 263-75, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17465991

RESUMO

Spinal cord injury (SCI) typically results from sustained trauma to the spinal cord, resulting in loss of neurologic function at the level of the injury. However, activation of various physiological mechanisms secondary to the initial trauma including edema, inflammation, excito-toxicity, excessive cytokine release and apoptosis may exacerbate the injury and/or retard natural repair mechanisms. Herein, we demonstrate that cytoplasmic extracts prepared from adipose tissue stromal cells (ATSCs) inhibits H(2)O(2)-mediated apoptosis of cultured spinal cord-derived neural progenitor cells (NPCs) resulting in increased cell survival. The ATSC extracts mediated this effect by decreasing caspase-3 and c-Jun-NH2-terminal kinase (SAPK/JNK) activity, inhibiting cytochrome c release from mitochondria and reducing Bax expression levels in cells. Direct injection of ATSC extracts mixed with Matrigel into the spinal cord immediately after SCI also resulted in reduced apoptotic cell death, astrogliosis and hypo-myelination but did not reduce the extent of microglia infiltration. Moreover, animals injected with the ATSC extract showed significant functional improvement of hind limbs as measured by the BBB (Basso, Beattie and Bresnahan) scale. Collectively, these studies show a prominent therapeutic effect of ATSC cytoplasmic extracts on SCI principally caused by an inhibition of apoptosis-mediated cell death, which spares white matter, oligodendrocytes and neurons at the site of injury. The ability of ATSC extracts to prevent secondary pathological events and improve neurologic function after SCI suggests that extracts prepared from autologous cells harvested from SCI patients may have clinical utility.


Assuntos
Tecido Adiposo/patologia , Apoptose/efeitos dos fármacos , Extratos Celulares/uso terapêutico , Citoplasma/química , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Animais , Caspase 3/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Peróxido de Hidrogênio/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Traumatismos da Medula Espinal/patologia , Células-Tronco/efeitos dos fármacos , Células Estromais/patologia , Proteína X Associada a bcl-2/metabolismo
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