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1.
Nat Commun ; 11(1): 4504, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908131

RESUMO

The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.


Assuntos
Microambiente Celular/imunologia , Sistemas de Liberação de Medicamentos/instrumentação , Fator de Crescimento Neural/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Traumatismos da Medula Espinal/terapia , Tecidos Suporte , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Preparações de Ação Retardada/administração & dosagem , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Interleucina-4/administração & dosagem , Lipossomos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Fator de Crescimento Neural/farmacocinética , Regeneração Nervosa/imunologia , Ratos , Recuperação de Função Fisiológica/imunologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Traumatismos da Medula Espinal/imunologia
2.
Plast Reconstr Surg ; 146(2): 309-320, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32740581

RESUMO

BACKGROUND: Adipose-derived stem cells are considered as candidate cells for regenerative plastic surgery. Measures to influence cellular properties and thereby direct their regenerative potential remain elusive. Hyperbaric oxygen therapy-the exposure to 100% oxygen at an increased atmospheric pressure-has been propagated as a noninvasive treatment for a multitude of indications and presents a potential option to condition cells for tissue-engineering purposes. The present study evaluates the effect of hyperbaric oxygen therapy on human adipose-derived stem cells. METHODS: Human adipose-derived stem cells from healthy donors were treated with hyperbaric oxygen therapy at 2 and 3 atm. Viability before and after each hyperbaric oxygen therapy, proliferation, expression of surface markers and protein contents of transforming growth factor (TGF)-ß, tumor necrosis factor-α, hepatocyte growth factor, and epithelial growth factor in the supernatants of treated adipose-derived stem cells were measured. Lastly, adipogenic, osteogenic, and chondrogenic differentiation with and without use of differentiation-inducing media (i.e., autodifferentiation) was examined. RESULTS: Hyperbaric oxygen therapy with 3 atm increased viability, proliferation, and CD34 expression and reduced the CD31/CD34/CD45 adipose-derived stem cell subset and endothelial progenitor cell population. TGF-ß levels were significantly decreased after two hyperbaric oxygen therapy sessions in the 2-atm group and decreased after three hyperbaric oxygen therapy sessions in the 3-atm group. Hepatocyte growth factor secretion remained unaltered in all groups. Although the osteogenic and chondrogenic differentiation were not influenced, adipogenic differentiation and autodifferentiation were significantly enhanced, with osteogenic autodifferentiation significantly alleviated by hyperbaric oxygen therapy with 3 atm. CONCLUSION: Hyperbaric oxygen therapy with 3 atm increases viability and proliferation of adipose-derived stem cells, alters marker expression and subpopulations, decreases TGF-ß secretion, and skews adipose-derived stem cells toward adipogenic differentiation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.


Assuntos
Adipogenia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Engenharia Celular/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Oxigênio/administração & dosagem , Tecido Adiposo/citologia , Adulto , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Pressão , Cultura Primária de Células/métodos
3.
Nat Commun ; 11(1): 3953, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769974

RESUMO

Many important cell types in adult vertebrates have a mesenchymal origin, including fibroblasts and vascular mural cells. Although their biological importance is undisputed, the level of mesenchymal cell heterogeneity within and between organs, while appreciated, has not been analyzed in detail. Here, we compare single-cell transcriptional profiles of fibroblasts and vascular mural cells across four murine muscular organs: heart, skeletal muscle, intestine and bladder. We reveal gene expression signatures that demarcate fibroblasts from mural cells and provide molecular signatures for cell subtype identification. We observe striking inter- and intra-organ heterogeneity amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) and regulatory signaling circuits. Our data shed new light on the diversity of poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes.


Assuntos
Diferenciação Celular , Fibroblastos/fisiologia , Células-Tronco Mesenquimais/fisiologia , Miócitos de Músculo Liso/fisiologia , Pericitos/fisiologia , Animais , Separação Celular , Vasos Coronários/citologia , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Citometria de Fluxo , Intestinos/irrigação sanguínea , Intestinos/citologia , Masculino , Camundongos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/citologia , Músculo Liso Vascular/citologia , Miocárdio/citologia , Miócitos de Músculo Liso/citologia , Pericitos/citologia , RNA-Seq , Análise de Célula Única , Bexiga Urinária/irrigação sanguínea , Bexiga Urinária/citologia
4.
PLoS One ; 15(8): e0238132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853221

RESUMO

Bears do not suffer from osteoporosis during hibernation, which is associated with long-term inactivity, lack of food intake, and cold exposure. However, the mechanisms involved in bone loss prevention have scarcely been elucidated in bears. We investigated the effect of serum from hibernating Japanese black bears (Ursus thibetanus japonicus) on differentiation of peripheral blood mononuclear cells (PBMCs) to osteoclasts (OCs). PBMCs collected from 3 bears were separately cultured with 10% serum of 4 active and 4 hibernating bears (each individual serum type was assessed separately by a bear PBMCs), and differentiation were induced by treatment with macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL). PBMCs that were cultured with the active bear serum containing medium (ABSM) differentiated to multi-nucleated OCs, and were positive for TRAP stain. However, cells supplemented with hibernating bear serum containing medium (HBSM) failed to form OCs, and showed significantly lower TRAP stain (p < 0.001). On the other hand, HBSM induced proliferation of adipose derived mesenchymal stem cells (ADSCs) similarly to ABSM (p > 0.05), indicating no difference on cell growth. It was revealed that osteoclastogenesis of PBMCs is hindered by HBSM, implying an underlying mechanism for the suppressed bone resorption during hibernation in bears. In addition, this study for the first time showed the formation of bears' OCs in-vitro.


Assuntos
Hibernação/fisiologia , Osteoclastos/fisiologia , Osteogênese/fisiologia , Ursidae/fisiologia , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/fisiopatologia , Diferenciação Celular/fisiologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/fisiologia , Fator Estimulador de Colônias de Macrófagos/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Osteoclastos/metabolismo , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Ursidae/metabolismo
6.
Life Sci ; 257: 118017, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32603821

RESUMO

AIMS: Mesenchymal stem cell (MSC)-derived exosomes (MSCs-exos) regulate biological functions in different diseases, such as liver fibrosis, diabetes, and ischaemic heart injury. However, the function of MSC-derived exosomes on the intestinal barrier and the underlying mechanisms are poorly characterized. MAIN METHODS: The expression of miR-34a/c-5p, miR-29b-3p and Claudin-3 in human normal intestinal tissues and damaged intestinal tissues was evaluated by RT-qPCR. The effect of MSC-secreted exosomes on Claudins in Caco-2 cells was measured by using confocal microscopy, RT-qPCR and Western blot. Dual luciferase reporter assays and RNA immunoprecipitation (RIP) assays were performed to study the interaction between miR-34a/c-5p, miR-29b-3p and Snail. I/R-induced intestinal damage in rats was used to determine the in vivo effect of MSC-exos on intestinal barrier function. KEY FINDINGS: In this study, we found that miR-34a/c-5p, miR-29b-3p and Claudin-3 were downregulated in damaged human intestinal tissues. MSC-exos increased the expression of Claudin-3, Claudin-2 and ZO-1 in Caco-2 cells. Further studies demonstrated that MSC-exos promoted Claudin-3, Claudin-2 and ZO-1 expression in Caco-2 cells by Snail, which was targeted by miR-34a/c-5p and miR-29b-3p. In vivo experiments showed that MSC-derived exosomes could improve I/R-induced intestinal damage through the Snail/Claudins signaling pathway. SIGNIFICANCE: The findings here suggest a novel molecular basis for the therapy of intestinal barrier dysfunction.


Assuntos
Mucosa Intestinal/metabolismo , MicroRNAs/genética , Animais , Condrócitos/metabolismo , Claudinas/metabolismo , Exossomos/genética , Exossomos/metabolismo , Humanos , Intestinos/fisiologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , MicroRNAs/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/metabolismo
7.
Life Sci ; 257: 118038, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622947

RESUMO

PURPOSE: The importance of regeneration in large bone defects forces the orthopedic surgeons to search for a proper methodology. The present experiment evaluated the capability of polylactic acid/polycaprolactone/hydroxyapatite (PLA/PCL/HA) scaffold loaded with and without mesenchymal stem cells (MSCs) on bone regeneration. METHODS: Fourier transform infrared spectrometry, X-ray diffraction, scanning electron microscopy, and rheology methodologies were used to characterize the scaffold. Forty Wistar rats were randomly divided into the four groups including the untreated defects as the control group and three other groups in which the bone defects were treated with autologous bones (autograft group), the PLA/PCL/HA scaffolds (PLA/PCL/HA group), and the MSCs-seeded scaffolds (MSCs-seeded PLA/PCL/HA group). RESULTS: Based on the qRT-PCR results, significantly higher expression levels of osteocalcin, osteopontin, and CD31 were seen in the cell-seeded scaffold group compared to the control group (P < 0.05). The CT scanning and radiographic images depicted significantly more newly formed bonny tissue in the MSCs-loaded scaffold and autograft groups than the untreated group (P < 0.001). The immunohistochemistry, biomechanical, histopathologic, and histomorphometric evaluations demonstrated significantly improved regeneration in the autograft and MSCs-loaded scaffold groups compared to the non-treated group (P < 0.05). There were significant differences between the scaffold and untreated groups in all in vivo evaluations (P < 0.05). CONCLUSION: The MSCs enhanced bone healing potential of the PLA/PCL/HA scaffold and the MSCs-seeded scaffold was comparable to the autograft as the golden treatment regimen (P > 0.05).


Assuntos
Regeneração Óssea/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Engenharia Tecidual/métodos , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Durapatita/química , Masculino , Células-Tronco Mesenquimais/fisiologia , Poliésteres/química , Rádio (Anatomia)/metabolismo , Ratos , Ratos Wistar , Tecidos Suporte/química
8.
Curr Res Transl Med ; 68(3): 105-110, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32616467

RESUMO

The relative ease of isolation of mesenchymal stem cells (MSCs) from different tissues coupled with their culture expansion in vitro and their differentiation capacity to mesodermal, endodermal and ectodermal lineages have made these cells attractive for a large number of therapeutic applications. In recent years, there has been remarkable progress in the utilization of MSCs in diverse clinical indications both in animal models and human clinical trials. However, the potential of MSCs to control or treat viral diseases is still in its infancy. In this study, we report quantitative data on the MSC-based clinical trials over the last ten years as they appear on the online database of clinical research studies from US National Institutes of Health. In particular, we provide comprehensive review of either completed or ongoing clinical trials using MSCs for virus-associated diseases focusing on HIV, hepatitis B virus and COVID-19 virus.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Viroses/terapia , Fenômenos Fisiológicos Virais , Animais , Betacoronavirus/fisiologia , Técnicas de Cultura de Células , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , HIV/fisiologia , Vírus da Hepatite B/fisiologia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/tendências , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Viroses/epidemiologia , Viroses/imunologia , Vírus/patogenicidade
10.
Rev. osteoporos. metab. miner. (Internet) ; 12(2): 40-44, abr.-jun. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193782

RESUMO

OBJETIVO: Las células madre mesenquimales (MSCs) son atractivas en la terapia regenerativa de patologías humanas. En los modelos murinos, en los que se trasplantan MSCs humanas, es muy importante poder distinguir el origen de las MSCs identificadas en los órganos de ratones. El objetivo de este estudio fue determinar el rendimiento del análisis basado en PCR de secuencias Alu humanas para detectar ADN humano después de la infusión de células madre de médula ósea humana (hBMSCs) en ratones inmunodeficientes. MATERIAL Y MÉTODO: Las hBMSCs se obtuvieron de la cabeza femoral de pacientes sometidos a cirugía de reemplazo de cadera. Se infundieron 106 hBMSCs por vía intravenosa mediante inyección en el seno retro-orbitario de ratones NOD/SCID. Después se evaluó la presencia de ADN humano en pulmón, hígado y hueso. RESULTADOS: En mezclas de ADN in vitro, el ADN humano se detectó fácilmente con una buena relación logarítmica-lineal. De manera similar, cuando se mezclaron osteoblastos humanos y de ratón, se detectaron fácilmente 1-10 células humanas entre 105 células de ratón. Asimismo, se detectó el ADN humano en los pulmones 1 y 7 días después de las infusiones celulares en ratones NOD/SCID. Sin embargo, el ADN humano se detectó de manera inconsistente en el hígado y los huesos. CONCLUSIÓN: La detección de secuencias Alu es un procedimiento eficaz para detectar ADN humano. Los resultados confirman que la mayoría de las hBMSCs inyectadas por vía intravenosa quedan atrapadas en los pulmones. Por lo tanto, de cara al tratamiento de trastornos esqueléticos, se necesitan procedimientos para aumentar la migración de dichas células al hueso


OBJETIVE: Mesenchymal stem cells (MSCs) are commonly used in regenerative therapy of human diseases. In murine models, in which human MSCs are transplanted, distinguishing the origin of the identified MSCs in the organs of mice is important. The objective of this study was to determine the performance of PCR-based analysis of human Alu sequences to detect human DNA after infusion of human bone marrow stem cells (hBMSCs) in immunodeficient mice. MATERIAL AND METHOD: HBMSCs were obtained from the femoral head of patients undergoing hip replacement surgery. 106 hBMSCs were infused intravenously by injection into the retro-orbital sinus of NOD/SCID mice. The presence of human DNA in lung, liver and bone was then assessed. RESULTS: In in vitro DNA mixtures, human DNA was easily detected with a good logarithmic-linear relationship. Similarly, when human and mouse osteoblasts were mixed, 1-10 cells were easily detected among 105 mouse cells. Likewise, human DNA was detected in the lungs 1 and 7 days after cell infusions in NOD/SCID mice. However, human DNA was inconsistently detected in the liver and bones. CONCLUSION: Detecting Alu sequences is an effective procedure to observe human DNA. The results confirm that most intravenously injected hBMSCs are trapped in the lungs. Thus, for the treatment of skeletal disorders, procedures are needed to increase the migration of these cells to the bone


Assuntos
Humanos , Camundongos , Movimento Celular/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , DNA/análise , Reação em Cadeia da Polimerase , Modelos Animais
11.
Protein Cell ; 11(10): 707-722, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32519302

RESUMO

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Transplante de Células-Tronco Mesenquimais , Pandemias , Pneumonia Viral/complicações , Síndrome do Desconforto Respiratório do Adulto/terapia , Transferência Adotiva , Células Epiteliais Alveolares/patologia , Animais , Apoptose , Líquidos Corporais/metabolismo , Linfócitos T CD4-Positivos/imunologia , Ensaios Clínicos como Assunto , Coinfecção/prevenção & controle , Coinfecção/terapia , Infecções por Coronavirus/imunologia , Modelos Animais de Doenças , Células Endoteliais/patologia , Oxigenação por Membrana Extracorpórea , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Vetores Genéticos/uso terapêutico , Humanos , Imunidade Inata , Mediadores da Inflamação/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , Pneumonia Viral/imunologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/patologia , Pesquisa Médica Translacional
12.
Science ; 368(6490): 497-505, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32355025

RESUMO

Androgen deprivation is the cornerstone of prostate cancer treatment. It results in involution of the normal gland to ~90% of its original size because of the loss of luminal cells. The prostate regenerates when androgen is restored, a process postulated to involve stem cells. Using single-cell RNA sequencing, we identified a rare luminal population in the mouse prostate that expresses stemlike genes (Sca1 + and Psca +) and a large population of differentiated cells (Nkx3.1 +, Pbsn +). In organoids and in mice, both populations contribute equally to prostate regeneration, partly through androgen-driven expression of growth factors (Nrg2, Rspo3) by mesenchymal cells acting in a paracrine fashion on luminal cells. Analysis of human prostate tissue revealed similar differentiated and stemlike luminal subpopulations that likewise acquire enhanced regenerative potential after androgen ablation. We propose that prostate regeneration is driven by nearly all persisting luminal cells, not just by rare stem cells.


Assuntos
Androgênios/metabolismo , Próstata/fisiologia , Próstata/cirurgia , Neoplasias da Próstata/cirurgia , Regeneração , Antagonistas de Androgênios/uso terapêutico , Proteína de Ligação a Androgênios/genética , Animais , Antígenos de Neoplasias/genética , Ataxina-1/genética , Diferenciação Celular/genética , Proteínas Ligadas por GPI/genética , Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Masculino , Células-Tronco Mesenquimais/fisiologia , Camundongos , Proteínas de Neoplasias/genética , Fatores de Crescimento Neural/genética , Tamanho do Órgão , Organoides/metabolismo , Organoides/fisiologia , Próstata/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Regeneração/genética , Análise de Sequência de RNA , Análise de Célula Única , Trombospondinas/genética , Fatores de Transcrição/genética
14.
PLoS One ; 15(5): e0228510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407317

RESUMO

Mesenchymal stem cells have the ability to transdifferentiate into neurons and therefore one of the potential adult stem cell source for neuronal tissue regeneration applications and understanding neurodevelopmental processes. In many studies on human mesenchymal stem cell (hMSC) derived neurons, success in neuronal differentiation was limited to neuronal protein expressions which is not statisfactory in terms of neuronal activity. Established neuronal networks seen in culture have to be investigated in terms of synaptic signal transmission ability to develop a culture model for human neurons and further studying the mechanism of neuronal differentiation and neurological pathologies. Accordingly, in this study, we analysed the functionality of bone marrow hMSCs differentiated into neurons by a single step cytokine-based induction protocol. Neurons from both primary hMSCs and hMSC cell line displayed spontaneous activity (≥75%) as demonstrated by Ca++ imaging. Furthermore, when electrically stimulated, hMSC derived neurons (hMd-Neurons) matched the response of a typical neuron in the process of maturation. Our results reveal that a combination of neuronal inducers enhance differentiation capacity of bone marrow hMSCs into high yielding functional neurons with spontaneous activity and mature into electrophysiologically active state. Conceptually, we suggest these functional hMd-Neurons to be used as a tool for disease modelling of neuropathologies and neuronal differentiation studies.


Assuntos
Células-Tronco Adultas/citologia , Diferenciação Celular/genética , Células-Tronco Mesenquimais/citologia , Neurônios/citologia , Células-Tronco Adultas/fisiologia , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Linhagem da Célula/genética , Células Cultivadas , Fenômenos Eletrofisiológicos , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Neurônios/fisiologia
15.
PLoS One ; 15(5): e0232899, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392240

RESUMO

Various nanopatterning techniques have been developed to improve cell proliferation and differentiation efficiency. As we previously reported, nanopillars and pores are able to sustain human pluripotent stem cells and differentiate pancreatic cells. From this, the nanoscale patterns would be effective environment for the co-culturing of epithelial and mesenchymal cell types. Interestingly, the nanopatterning selectively reduced the proliferative rate of mesenchymal cells while increasing the expression of adhesion protein in epithelial type cells. Additionally, co-cultured cells on the nanopatterning were not negatively affected in terms of cell function metabolic ability or cell survival. This is in contrast to conventional co-culturing methods such as ultraviolet or chemical treatments. The nanopatterning appears to be an effective environment for mesenchymal co-cultures with typically low proliferative rates cells such as astrocytes, neurons, melanocytes, and fibroblasts without using potentially damaging treatments.


Assuntos
Técnicas de Cocultura/instrumentação , Células Epiteliais , Células-Tronco Mesenquimais , Nanoestruturas , Animais , Adesão Celular , Proliferação de Células , Sobrevivência Celular , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Fibroblastos/citologia , Fibroblastos/fisiologia , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Camundongos , Propriedades de Superfície
16.
Hum Cell ; 33(3): 652-662, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32350750

RESUMO

The tumor microenvironment (TM) is an essential factor of tumor progression. Mesenchymal stem cells (MSCs) are important components of the TM and play critical roles in cancer metastasis. Resveratrol (RES) is a potential antitumor drug that has attracted extensive attention. However, it remains unclear whether RES can exert its antitumor activity by targeting MSCs located in the TM. In this study, we demonstrated that the conditioned medium of gastric-cancer-derived MSCs (GC-MSCs) promoted gastric cancer (GC) metastasis and facilitated the progression of epithelialmesenchymal transition (EMT) of GC cells. However, after pretreatment with RES, the prometastatic effect of GC-MSCs on GC cells was reversed. Furthermore, RES reduced GC-MSC (IL-6, IL-8, MCP-1, VEGF) gene expression and protein secretion, and counteracted the activation of the GC-MSC-induced Wnt/ß-catenin signaling of GC cells, with less ß-catenin nuclear transport and declined expression of ß-catenin, CD44, and CyclinD3 in GC cells. Re-expression of ß-catenin impaired the inhibitory effect of RES on GC cells. In conclusion, RES restricted the mobility increase of GC cells and reversed the progress of EMT induced by GC-MSCs by inactivating the Wnt/ß-catenin signaling. GC-MSCs are promising target for RES in the inhibition of GC metastasis.


Assuntos
Células-Tronco Mesenquimais/fisiologia , Metástase Neoplásica/tratamento farmacológico , Resveratrol/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos Fitogênicos , Linhagem Celular Tumoral , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Células-Tronco Mesenquimais/patologia , Terapia de Alvo Molecular , Fitoterapia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Microambiente Tumoral , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
17.
Hum Cell ; 33(3): 444-458, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32378164

RESUMO

Mesenchymal stem cells (MSCs) possess the capabilities of self-renewal and multipotent differentiation. Firstly isolated from bone marrow, MSCs are subsequently identified from various post-natal tissue types. Based the differentiation into tissue-specific cells, MSCs were capable of replacing damaged and diseased tissues. In addition, MSCs have been demonstrated to possess important immunomodulatory properties. Increasing data showed that MSCs exhibited tropism for sites of the tumor microenvironment and interacted with tumor cells closely through paracrine signaling. Therefore, better understanding of crosstalk between MSCs and tumor cells will be able to develop potential strategies in the treatment of tumors in the future. Herein, we summarize the research progress of the influence of MSCs on tumor cells and the prospect of their application in tumor therapy in this review.


Assuntos
Células-Tronco Mesenquimais/fisiologia , Neoplasias/terapia , Microambiente Tumoral/fisiologia , Células da Medula Óssea , Comunicação Celular , Diferenciação Celular , Imunomodulação , Células-Tronco Mesenquimais/imunologia
18.
Hum Cell ; 33(3): 470-475, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32447573

RESUMO

Osteoarthritis is a chronic degenerative joint disease with an incidence of 81% among people aged over 65 years in China. Osteoarthritis significantly decreases the quality of life of patients, causing physical and psychological damage and posing a serious economic burden. Clinical treatments for osteoarthritis include drug and surgical treatments. Drug treatment can successfully alleviate pain but not satisfactorily reverse joint damage, while surgical intervention is typically used to treat end-stage disease. Stem cells are multi-potential progenitor cells with self-renewal and multi-lineage differentiation abilities, and can differentiate into many kinds of cells, including chondrocytes. Umbilical cord stem cells, also known as Wharton's jelly mesenchymal stem cells (WJ-MSCs), have become the first choice for cartilage regeneration engineering owing to their availability and convenience of collection. This article reviews the biological characterization of WJ-MSCs in recent years, their advantages compared with other stem cells, and their application in the treatment of osteoarthritis in animal experiments and clinical trials.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Osteoartrite/terapia , Animais , Diferenciação Celular , Células Cultivadas , Sangue Fetal/citologia , Humanos , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/fisiologia
19.
Res Vet Sci ; 131: 222-231, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32413795

RESUMO

Skin lesions are normal to all species, regardless of gender or age. The skin, the largest organ of the body, has function as a primary barrier to the chemical, physical and biological aggressions of the environment. In animals, these lesions may be due to fights and/or predations, also as in humans, there is a very common cause of dermal lesions that are caused by burns and carcinomas. Looking for new techniques of tissue bioengineering, studies have been shown promising results for formulations of acellular biological scaffolds from tissue decellularization for the reconstitution of these lesions. The decellularization has its proof by a varied range of tests such as scanning electron microscopy and residual genomic DNA tests. Subsequently the tissue can go through the process of recellularization using cells of interest, even the animal that will receive this tissue, reducing the risks of rejection and improving the response to tissue transplantation. Thus, this manuscript aimed at the decellularization of the tissue with the use of chemical and physical means followed by sterilization and the establishment of a protocol for the recellularization of a decellularized scaffold from the Wistar rat dermis using murine fibroblasts and mesenchymal stem cells from canine adipose tissue for 7 days. After efficacy tests, the tissue recellularization were confirmed by immunofluorescence assays and scanning electron microscopy where the adherence of the cells in the biological scaffold was observed.


Assuntos
Derme , Fibroblastos/fisiologia , Células-Tronco Mesenquimais/fisiologia , Engenharia Tecidual/métodos , Tecidos Suporte , Animais , Cães , Camundongos , Ratos , Ratos Wistar
20.
Cell Prolif ; 53(5): e12803, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32246537

RESUMO

OBJECTIVES: The aim of this study is to investigate the role of sensory nerve in tooth homeostasis and its effect on mesenchymal stromal/stem cells (MSCs) in dental pulp. MATERIALS AND METHODS: We established the rat denervated incisor models to identify the morphological and histological changes of tooth. The groups were as follows: IANx (inferior alveolar nerve section), SCGx (superior cervical ganglion removal), IANx + SCGx and Sham group. The biological behaviour of dental pulp stromal/stem cells (DPSCs) was evaluated. Finally, we applied activin B to DPSCs from sensory nerve-deficient microenvironment to analyse the changes of proliferation and apoptosis. RESULTS: Incisor of IANx and IANx + SCGx groups exhibited obvious disorganized tooth structure, while SCGx group only showed slight decrease of dentin thickness, implying sensory nerve, not sympathetic nerve, contributes to the tooth homeostasis. Moreover, we found sensory nerve injury led to disfunction of DPSCs via activin B/SMAD2/3 signalling in vitro. Supplementing activin B promoted proliferation and reduced apoptosis of DPSCs in sensory nerve-deficient microenvironment. CONCLUSIONS: This research first demonstrates that sensory nerve-deficient microenvironment impairs tooth haemostasis by inducing apoptosis of DPSCs via activin B/SMAD2/3 signalling. Our study provides the evidence for the crucial role of sensory nerve in tooth homeostasis.


Assuntos
Apoptose/fisiologia , Polpa Dentária/fisiologia , Homeostase/fisiologia , Células Receptoras Sensoriais/fisiologia , Células-Tronco/fisiologia , Dente/fisiologia , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Microambiente Celular/fisiologia , Técnicas de Cocultura/métodos , Polpa Dentária/metabolismo , Dentina/metabolismo , Dentina/fisiologia , Feminino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo , Dente/metabolismo
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