Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.437
Filtrar
1.
Med Sci (Paris) ; 36 Hors série n° 1: 61-66, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-33052097

RESUMO

Most prevalent cancers are of epithelial origin and their morbidity often results from secondary tumors. Cancer aggressiveness relates to intratumoral heterogeneity, including rare tumor initiating cells that share many features with adult stem cells. Both normal and cancer stem cells are characterized by their plasticity between epithelial and mesenchymal phenotypes, progressing through a series of reversible intermediates. While a core of regulators (Snail, Zeb1-2,...) is renowned to promote epithelial to mesenchyme transition (EMT), OvoL/Shavenbaby factors now emerge as a family of key epithelial stabilizers. Therefore, pro-EMT and OvoL/Shavenbaby transcription factors could provide a molecular rheostat to control stemness and epithelial-mesenchyme plasticity. We address this question in flies, in which the unique OvoL/Shavenbaby factor offers a powerful in vivo paradigm for functional analyses. Our results show that Shavenbaby is critical for adult stem cell homeostasis, and directly interacts with the Hippo pathway to protect stem cells from death.


Assuntos
Células-Tronco Adultas/fisiologia , Proteínas de Ligação a DNA/fisiologia , Transição Epitelial-Mesenquimal/genética , Células-Tronco Neoplásicas/fisiologia , Fatores de Transcrição/fisiologia , Células-Tronco Adultas/metabolismo , Animais , Plasticidade Celular/genética , Proteínas de Ligação a DNA/genética , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiologia , Humanos , Família Multigênica/genética , Neoplasias/genética , Neoplasias/patologia , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/genética
2.
Nat Commun ; 11(1): 4275, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32848155

RESUMO

New neurons are generated in adult mammals. Adult hippocampal neurogenesis is considered to play an important role in cognition and mental health. The number and properties of newly born neurons are regulatable by a broad range of physiological and pathological conditions. To begin to understand the underlying cellular mechanisms and functional relevance of adult neurogenesis, many studies rely on quantification of adult-born neurons. However, lack of standardized methods to quantify new neurons is impeding research reproducibility across laboratories. Here, we review the importance of stereology, and propose why and how it should be applied to the study of adult neurogenesis.


Assuntos
Encéfalo/citologia , Encéfalo/fisiologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Adulto , Células-Tronco Adultas/citologia , Células-Tronco Adultas/fisiologia , Animais , Giro Denteado/citologia , Giro Denteado/fisiologia , Humanos , Modelos Neurológicos , Plasticidade Neuronal
4.
Med Sci (Paris) ; 36(6-7): 581-591, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32614308

RESUMO

Following partial or total loss of peripheral vestibular inputs, a phenomenon called central vestibular compensation takes place in the hours and days following the injury. This neuroplasticity process involves a mosaic of profound rearrangements within the brain stem vestibular nuclei. Among them, the setting of a new neuronal network is maybe the most original and unexpected, as it involves an adult reactive neurogenesis in a brain area not reported as neurogenic so far. Both the survival and functionality of this newly generated neuronal network will depend on its integration to pre-existing networks in the deafferented structure. Far from being aberrant, this new structural organization allows the use of inputs from other sensory modalities (vision and proprioception) to promote the restoration of the posture and equilibrium. We choose here to detail this model, which does not belong to the traditional niches of adult neurogenesis, but it is the best example so far of the reparative role of the adult neurogenesis. Not only it represents an original neuroplasticity mechanism, interesting for basic neuroscience, but it also opens new medical perspectives for the development of therapeutic approaches to alleviate vestibular disorders.


Assuntos
Encéfalo/citologia , Neurogênese/fisiologia , Neurônios/fisiologia , Postura/fisiologia , Doenças Vestibulares/reabilitação , Núcleos Vestibulares/lesões , Adulto , Células-Tronco Adultas/citologia , Células-Tronco Adultas/fisiologia , Animais , Encéfalo/fisiologia , Humanos , Células-Tronco Neurais/fisiologia , Plasticidade Neuronal/fisiologia , Doenças Vestibulares/fisiopatologia , Núcleos Vestibulares/patologia , Núcleos Vestibulares/fisiologia , Vestíbulo do Labirinto/lesões , Vestíbulo do Labirinto/patologia , Vestíbulo do Labirinto/fisiologia
6.
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
7.
Nat Protoc ; 15(5): 1612-1627, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32238950

RESUMO

'Adult' or 'somatic' stem cells harbor an intrinsic ability to regenerate tissues. Heterogeneity of such stem cells along the gastrointestinal tract yields the known segmental specificity of this organ and may contribute to the pathology of certain enteric conditions. Here we detail technology for the generation of 'libraries' of clonogenic cells from 1-mm-diamter endoscopic biopsy samples from the human gastrointestinal tract. Each of the 150-300 independent clones in a typical stem cell library can be clonally expanded to billions of cells in a few weeks while maintaining genomic stability and the ability to undergo multipotent differentiation to the specific epithelia from which the sample originated. The key to this methodology is the intrinsic immortality of normal intestinal stem cells (ISCs) and culture systems that maintain them as highly immature, ground-state ISCs marked by a single-cell clonogenicity of 70% and a corresponding 250-fold proliferative advantage over spheroid technologies. Clonal approaches such as this enhance the resolution of molecular genetics, make genome editing easier, and may be useful in regenerative medicine, unravelling heterogeneity in disease, and facilitating drug discovery.


Assuntos
Células-Tronco Adultas/fisiologia , Técnicas de Cultura de Células , Mucosa Intestinal/citologia , Células 3T3 , Animais , Biópsia , Endoscopia Gastrointestinal , Humanos , Camundongos
8.
Cell ; 181(3): 492-494, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32234524

RESUMO

The 2020 Canada Gairdner International Award has been awarded to Elaine Fuchs for her discovery of the role of adult skin stem cells in homeostasis, wound repair, inflammation, and cancer. These insights have established a foundation for basic knowledge on how adult stem cells form, maintain, and repair tissues and have provided the groundwork for additional exploration and discovery of pathways in other stem cell systems.


Assuntos
Células-Tronco Adultas/metabolismo , Células-Tronco Adultas/fisiologia , Pele/metabolismo , Animais , Distinções e Prêmios , Canadá , Células Epidérmicas/metabolismo , Feminino , História do Século XX , História do Século XXI , Homeostase/fisiologia , Humanos , Neoplasias/metabolismo , Cicatrização/fisiologia
9.
Curr Pharm Biotechnol ; 21(12): 1154-1164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32297579

RESUMO

BACKGROUND: Stem cells are of two types: embryonic and adult stem cells and they act as a repair system by replenishing body tissue. Stem cells differentiate into different types of cells, such as neural, hematopoietic, adipose, etc. and are used for the treatment of various conditions like myocardial infarction, spinal cord injury, Parkinson's disease and diabetes. METHODS: This article focuses on recent research development that addresses the viability issues of stem cells. The efficiency of transplanted stem cells reduces due to conditions like hypoxia, inflammation, nutrient deprivation, immunogenicity, extracellular matrix loss on delivery and mechanical stress. RESULTS: To increase the viability of stem cells, techniques like scaffolds of stem cells with hydrogel or alginate, pre-conditioning, different routes of administration and encapsulation, are implemented. CONCLUSION: For the protection of stem cells against apoptosis, different pathways, namely Phosphoinositide 3-Kinase (PI3K/AKT), Hypoxia-Inducible Factor (HIF1), Mitogen-Activated Protein Kinases (MAPK) and Hippo, are discussed. DISCUSSION: Activation of the PI3K/AKT pathway decreases the concentration of apoptotic factors, while the HIF pathway protects stem cells against the micro-environment of tissue (hypoxia).


Assuntos
Células-Tronco Adultas/fisiologia , Técnicas de Cultura de Células/métodos , Células-Tronco Embrionárias/fisiologia , Células-Tronco Mesenquimais/fisiologia , Células-Tronco Adultas/efeitos dos fármacos , Células-Tronco Adultas/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Criopreservação , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Transplante de Células-Tronco
10.
Development ; 147(7)2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32165493

RESUMO

The vertebrate inner ear employs sensory hair cells and neurons to mediate hearing and balance. In mammals, damaged hair cells and neurons are not regenerated. In contrast, hair cells in the inner ear of zebrafish are produced throughout life and regenerate after trauma. However, it is unknown whether new sensory neurons are also formed in the adult zebrafish statoacoustic ganglion (SAG), the sensory ganglion connecting the inner ear to the brain. Using transgenic lines and marker analysis, we identify distinct cell populations and anatomical landmarks in the juvenile and adult SAG. In particular, we analyze a Neurod/Nestin-positive progenitor pool that produces large amounts of new neurons at juvenile stages, which transitions to a quiescent state in the adult SAG. Moreover, BrdU pulse chase experiments reveal the existence of a proliferative but otherwise marker-negative cell population that replenishes the Neurod/Nestin-positive progenitor pool at adult stages. Taken together, our study represents the first comprehensive characterization of the adult zebrafish SAG showing that zebrafish, in sharp contrast to mammals, display continued neurogenesis in the SAG well beyond embryonic and larval stages.


Assuntos
Células-Tronco Adultas/fisiologia , Orelha Interna/fisiologia , Gânglios Sensitivos/citologia , Células Ciliadas Auditivas/fisiologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Peixe-Zebra , Células-Tronco Adultas/citologia , Envelhecimento/fisiologia , Animais , Animais Geneticamente Modificados , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular/genética , Orelha Interna/citologia , Embrião não Mamífero , Gânglios Sensitivos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Células Ciliadas Auditivas/metabolismo , Larva , Proteínas do Tecido Nervoso/metabolismo , Nestina/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Células Receptoras Sensoriais/citologia , Células Receptoras Sensoriais/fisiologia , Nicho de Células-Tronco/fisiologia , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
11.
PLoS Genet ; 16(2): e1008613, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32078629

RESUMO

The extracellular matrix (ECM) is important for maintaining the boundaries between tissues. This role is particularly critical in the stem cell niche, as pre-neoplastic or cancerous stem cells must pass these boundaries in order to invade into the surrounding tissue. Here, we examine the role of the ECM as a regulator of the stem cell compartment in the planarian Schmidtea mediterranea, a highly regenerative, long-lived organism with a large population of adult stem cells. We identify two EGF repeat-containing genes, megf6 and hemicentin, with identical knockdown phenotypes. We find that megf6 and hemicentin are needed to maintain the structure of the basal lamina, and in the absence of either gene, pluripotent stem cells migrate ectopically outside of their compartment and hyper-proliferate, causing lesions in the body wall muscle. These muscle lesions and ectopic stem cells are also associated with ectopic gut branches, which protrude from the normal gut towards the dorsal side of the animal. Interestingly, both megf6 and hemicentin knockdown worms are capable of regenerating tissue free of both muscle lesions and ectopic cells, indicating that these genes are dispensable for regeneration. These results provide insight into the role of planarian ECM in restricting the stem cell compartment, and suggest that signals within the compartment may act to suppress stem cell hyperproliferation.


Assuntos
Células-Tronco Adultas/fisiologia , Genes de Helmintos/fisiologia , Platelmintos/fisiologia , Células-Tronco Pluripotentes/fisiologia , Nicho de Células-Tronco/genética , Animais , Animais Geneticamente Modificados , Movimento Celular/genética , Matriz Extracelular/metabolismo , Técnicas de Silenciamento de Genes , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Platelmintos/citologia , Regeneração/genética
13.
EMBO J ; 39(5): e101679, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32009252

RESUMO

Adult neural stem cells (NSCs) reside in specialized niches, which hold a balanced number of NSCs, their progeny, and other cells. How niche capacity is regulated to contain a specific number of NSCs remains unclear. Here, we show that ependyma-derived matricellular protein CCN1 (cellular communication network factor 1) negatively regulates niche capacity and NSC number in the adult ventricular-subventricular zone (V-SVZ). Adult ependyma-specific deletion of Ccn1 transiently enhanced NSC proliferation and reduced neuronal differentiation in mice, increasing the numbers of NSCs and NSC units. Although proliferation of NSCs and neurogenesis seen in Ccn1 knockout mice eventually returned to normal, the expanded NSC pool was maintained in the V-SVZ until old age. Inhibition of EGFR signaling prevented expansion of the NSC population observed in CCN1 deficient mice. Thus, ependyma-derived CCN1 restricts NSC expansion in the adult brain to maintain the proper niche capacity of the V-SVZ.


Assuntos
Proteína Rica em Cisteína 61/metabolismo , Neurogênese/fisiologia , Transdução de Sinais , Células-Tronco Adultas/fisiologia , Animais , Encéfalo , Proteína Rica em Cisteína 61/genética , Epêndima/citologia , Epêndima/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo
14.
J Mater Sci Mater Med ; 31(2): 13, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965357

RESUMO

Bioactive glasses have transformed healthcare due to their versatility. Bioactive borate glass, in particular, has shown remarkable healing properties for both hard and soft tissues. Incorporating dopants into the composition of bioactive glass helps to control mechanical properties, and it increases their usefulness for clinical applications. Using a bioactive borate glass, 13-93B3 (B3), we investigated eleven dopants on the viability and migration potential of adipose stem cells (ASCs), a therapeutic source of cells used in tissue engineering and cell therapy. Our results show that under standard cell culture conditions, only Cu-doped B3 decreased cell viability, while only Y-doped B3 attracted ASCs as it dissolved in cell culture media. Using a transwell invasion assay, priming ASCs with Co, Fe, Ga, I, Sr, or Zn-doped B3 increased their homing capacity. Because there is widespread interest in optimizing and enhancing the homing efficiency of ASCs and other therapeutic cells, we then tested if priming bone marrow mesenchymal stem cells (BMSCs) with dopants also increased their homing capacity. In the case of BMSCs, there was a significant increase in invasion when cells were primed with any of the doped-B3 glasses. This work shows that incorporating dopants into borate glasses can provide a platform for a safe and efficient method that stimulates endogenous cells and healing mechanisms.


Assuntos
Células-Tronco Adultas/fisiologia , Boratos/química , Vidro/química , Teste de Materiais , Células-Tronco Mesenquimais/fisiologia , Técnicas de Cultura de Células/instrumentação , Movimento Celular , Sobrevivência Celular , Humanos , Propriedades de Superfície , Engenharia Tecidual/métodos
15.
Neuron ; 104(5): 834-848, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31805262

RESUMO

Neural stem cells in the adult mammalian brain are the source of new neurons that contribute to complex sensory and cognitive functions. Most adult neural stem cells are maintained in a state of reversible cell cycle arrest, also called quiescence. Quiescent neural stem cells present a low rate of metabolic activity and a high sensitivity to their local signaling environment, and they can be activated by diverse physiological stimuli. The balance between stem cell quiescence and activity determines not only the rate of neurogenesis but also the long-term maintenance of the stem cell pool and the neurogenic capacity of the aging brain. In recent years, significant progress has been made in characterizing quiescent stem cells thanks to the introduction of new genomic and imaging techniques. We discuss in this review our current understanding of neural stem cell quiescence and its regulation by intrinsic and systemic factors.


Assuntos
Células-Tronco Adultas/citologia , Células-Tronco Adultas/fisiologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Animais , Humanos
16.
Nat Commun ; 10(1): 4966, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672973

RESUMO

Ovarian surface epithelium (OSE) undergoes recurring ovulatory rupture and repair. The OSE replenishing mechanism post ovulation remains unclear. Here we report that the expression of Protein C Receptor (Procr) marks a progenitor population in adult mice that is responsible for OSE repair post ovulation. Procr+ cells are the major cell source for OSE repair. The mechanism facilitating the rapid re-epithelialization is through the immediate expansion of Procr+ cells upon OSE rupture. Targeted ablation of Procr+ cells impedes the repairing process. Moreover, Procr+ cells displayed robust colony-formation capacity in culture, which we harnessed and established a long-term culture and expansion system of OSE cells. Finally, we show that Procr+ cells and previously reported Lgr5+ cells have distinct lineage tracing behavior in OSE homeostasis. Our study suggests that Procr marks progenitor cells that are critical for OSE ovulatory rupture and homeostasis, providing insight into how adult stem cells respond upon injury.


Assuntos
Células-Tronco Adultas/fisiologia , Receptor de Proteína C Endotelial/genética , Células Epiteliais/fisiologia , Epitélio/fisiologia , Ovário/fisiologia , Ovulação , Reepitelização/fisiologia , Células-Tronco Adultas/metabolismo , Animais , Autorrenovação Celular , Receptor de Proteína C Endotelial/metabolismo , Células Epiteliais/metabolismo , Epitélio/metabolismo , Feminino , Técnicas de Introdução de Genes , Camundongos , Ovário/citologia , Ovário/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo
17.
Elife ; 82019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31552825

RESUMO

Quiescence is essential for the long-term maintenance of adult stem cells but how stem cells maintain quiescence is poorly understood. Here, we show that neural stem cells (NSCs) in the adult mouse hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activated or quiescent states. We found that the inhibitor of DNA binding protein Id4 is enriched in quiescent NSCs and that elimination of Id4 results in abnormal accumulation of Ascl1 protein and premature stem cell activation. Accordingly, Id4 and other Id proteins promote elimination of Ascl1 protein in NSC cultures. Id4 sequesters Ascl1 heterodimerization partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of NSC quiescence and reveal a role for Id4 as a quiescence-inducing factor, in contrast with its role of promoting the proliferation of embryonic neural progenitors.


Assuntos
Células-Tronco Adultas/fisiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proliferação de Células , Hipocampo/citologia , Proteínas Inibidoras de Diferenciação/metabolismo , Células-Tronco Neurais/fisiologia , Animais , Células Cultivadas , Camundongos , Ligação Proteica , Fator 3 de Transcrição/metabolismo
18.
DNA Cell Biol ; 38(11): 1313-1322, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545082

RESUMO

This study investigated whether overexpression of paired-related homeobox 1 (prrx1) can successfully induce differentiation of brown adipose-derived stem cells (BADSCs) into sinus node-like cells. The experiments were performed in two groups: adenovirus-green fluorescent protein (Ad-GFP) group and Ad-prrx1 group. After 5-7 days of adenoviral transfection, the expression levels of sinus node cell-associated pacing protein (hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 [HCN4]) and ion channel (calcium channel, voltage-dependent, T type, alpha 1G subunit [Cacna1g]), as well as transcription factors (T-box 18 [TBX18], insulin gene enhancer binding protein 1 [ISL-1], paired-like homeodomain transcription factor 2 [pitx2], short stature homeobox 2 [shox2]), were detected by western blot and reverse transcription-quantitative polymerase chain reaction. Immunofluorescence assay was carried out to detect whether prrx1 was coexpressed with HCN4, TBX18, and ISL-1. Finally, whole-cell patch-clamp technique was used to record pacing current hyperpolarization-activated inward current (If). The isolated cells were CD90+, CD29+, and CD45-, indicating that pure BADSCs were successfully isolated. After 5-7 days of Ad transfection into cells, the mRNA levels and protein levels of pacing-related factors (TBX18, ISL-1, HCN4, shox2, and Cacna1g) in Ad-prrx1 group were significantly higher than those in Ad-GFP group. However, the expression level of pitx2 was decreased. Immunofluorescence analysis showed that prrx1 was coexpressed with TBX18, ISL-1, and HCN4 in the Ad-prrx1 group, which did not appear in the Ad-GFP group. Whole-cell patch clamps were able to record the If current in the experimental group rather than in the Ad-GFP group. Overexpression of prrx1 can successfully induce sinus node-like cells.


Assuntos
Tecido Adiposo Marrom/fisiologia , Células-Tronco Adultas/fisiologia , Diferenciação Celular/genética , Proteínas de Homeodomínio/fisiologia , Nó Sinoatrial/fisiologia , Tecido Adiposo Marrom/citologia , Células-Tronco Adultas/citologia , Animais , Transdiferenciação Celular/genética , Células Cultivadas , Masculino , Ratos , Ratos Sprague-Dawley , Nó Sinoatrial/citologia , Transfecção
19.
BMC Vet Res ; 15(1): 277, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375144

RESUMO

BACKGROUND: Little is known about the differences among adult and foetal equine mesenchymal stem cells (MSCs), and no data exist about their comparative ultrastructural morphology. The aim of this study was to describe and compare characteristics, immune properties, and ultrastructural morphology of equine adult (bone marrow: BM, and adipose tissue: AT) and foetal adnexa derived (umbilical cord blood: UCB, and Wharton's jelly: WJ) MSCs. RESULTS: No differences were observed in proliferation during the first 3 passages. While migration ability was similar among cells, foetal MSCs showed a higher adhesion ability, forming smaller spheroids after hanging drop culture (P < 0.05). All MSCs differentiated toward adipogenic, chondrogenic and osteogenic lineages, only tenogenic differentiation was less evident for WJ-MSCs. Data obtained by PCR confirmed MHC1 expression and lack of MHC2 expression in all four cell types. Foetal adnexa MSCs were positive for genes specific for anti-inflammatory and angiogenic factors (IL6, IL8, ILß1) and WJ-MSCs were the only positive for OCT4 pluripotency gene. At immunofluorescence all cells expressed typical mesenchymal markers (α-SMA, N-cadherin), except for BM-MSCs, which did not express N-cadherin. By transmission electron microscopy, it was observed that WJ-MSCs had a higher (P < 0.05) number of microvesicles compared to adult MSCs, and UCB-MSCs showed more microvesicles than BM-MSCs (P < 0.05). AT-MSCs had a lower number of mitochondria than WJ-MSCs (P < 0.05), and mitochondrial area was higher for WJ-MSCs compared to UCB and AT-MSCs (P < 0.05). CONCLUSIONS: Results demonstrate that MSCs from adult and foetal tissues have different characteristics, and foetal MSCs, particularly WJ derived ones, seem to have some charactestics that warrant further investigation into potential advantages for clinical application.


Assuntos
Células-Tronco Adultas/fisiologia , Sangue Fetal/citologia , Cavalos , Células-Tronco Mesenquimais , Geleia de Wharton/citologia , Animais , Diferenciação Celular , Ensaios de Migração Celular , Proliferação de Células , Senescência Celular
20.
PLoS One ; 14(7): e0219938, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31335913

RESUMO

Podoplanin (PDPN) is a glycoprotein that is expressed by various cell types, including keratinocytes, fibroblasts, and lymphatic endothelial cells. We found that PDPN is expressed in the hair follicle (HF) keratinocyte region and HF stem cell area during the late anagen phase but not during the telogen phase in mice. Importantly, keratinocyte-specific PDPN deletion in mice (K5-Cre;PDPNflox/flox) promoted anagen HF growth after depilation-induced HF regeneration as compared to control mice. RNA sequencing, followed by gene ontology analysis, showed down-regulation of focal adhesion and extracellular matrix interaction pathways in HF stem cells isolated from K5-Cre;PDPNflox/flox mice as compared to control mice. Furthermore, HF keratinocytes isolated from K5-Cre;PDPNflox/flox mice exhibited a decreased ability to interact with collagen type I in cell adhesion assays. Taken together, these results show that PDPN deletion promotes HF cycling, possibly via reduced focal adhesion and concomitantly enhanced migration of HF stem cells towards the bulb region. They also indicate potential new therapeutic strategies for the treatment of conditions associated with hair loss.


Assuntos
Folículo Piloso/crescimento & desenvolvimento , Glicoproteínas de Membrana/metabolismo , Células-Tronco Adultas/citologia , Células-Tronco Adultas/metabolismo , Células-Tronco Adultas/fisiologia , Animais , Movimento Celular , Células Cultivadas , Colágeno Tipo I/metabolismo , Matriz Extracelular/metabolismo , Feminino , Adesões Focais/metabolismo , Folículo Piloso/citologia , Folículo Piloso/metabolismo , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Queratinócitos/fisiologia , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA