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1.
Cell Physiol Biochem ; 53(5): 887-909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749350

RESUMO

Over the past years, the benefits of stem cell therapy approach for treatment of the cardiovascular diseases have been shown through the rebuilding of new cardiomyocytes and blood vessels. while a successful regeneration of the myocardium has been proven on the animal models of acute myocardial injuries resulted from the stem cells transplantation, no significant long-term regenerative with autologous stem cell therapy in patients with acute myocardial infarction have been reported based on recent meta-analyses. It seems that the inflammatory microenvironment of acute myocardial infarction has an inhibitory effect on the stem cells potential for regenerating the injured myocardium. Secretion of critical cytokines with pro-inflammatory properties including tumor necrosis factor-α, interleukin-1ß, and interleukin-6 as well as induction of hypoxic condition and finally formation of cytotoxic elements cause the cellular death and hinder the stem cells proliferation and differentiation. Based on the evidence, application of some approaches like co-delivery of mesenchymal stem cells with the other useful cells, using the stem cells derived productions, administration of preconditioned and modified cells, and also using the anti-inflammatory agents besides the cell therapy are hypothesized as the primary developed safe and practical approaches for decreasing destructive effects of the inflammation on the implanted stem/progenitor cells. In this review, we critically discuss the quiddity of the inflammatory microenvironment and its promoted mechanisms as the main elements to hinder the efficacy of stem cell therapy in the cases of acute myocardial infarction. Also, we finally propose some applied solutions to the problem of cardiac regeneration with stem cells therapy.


Assuntos
Infarto do Miocárdio/terapia , Transplante de Células-Tronco , Terapia Baseada em Transplante de Células e Tecidos , Microambiente Celular , Ensaios Clínicos como Assunto , Citocinas/metabolismo , Coração/fisiologia , Humanos , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Regeneração/fisiologia , Células-Tronco/citologia , Células-Tronco/metabolismo
2.
Invest Ophthalmol Vis Sci ; 60(13): 4436-4450, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31652328

RESUMO

Purpose: The purpose of this study was to systematically characterize and correlate the transcriptome and DNA methylome signatures of mouse Müller cells that may underlie the development, physiological functions, and regeneration capacity of these cells. Methods: Mouse Müller cells under normal, injury, and aging conditions were sorted from Müller cell-specific green fluorescent protein (GFP)-expressing mice. RNA sequencing was used to sequence transcriptomes, and reduced representation bisulfite sequencing was used to sequence DNA methylomes. Various bioinformatics tools were used to compare and correlate the transcriptomes and DNA methylomes. Results: Müller cells express a distinct transcriptome that is in line with their retinal supporting roles and dormant retinogenic status. Injury changes the Müller cell transcriptome dramatically but fails to stimulate the cell cycle machinery and retinogenic factors to the states observed in early retinal progenitor cells (RPCs). Müller cells exhibit a less methylated genome than that of early RPCs, but most regulatory elements for Müller cell- and RPC-specific genes are similarly hypomethylated in both Müller cells and RPCs, except for a subset of Müller cell-specific functional genes. Aging only subtly affects the transcriptome and DNA methylome of Müller cells. Conclusions: Failure to reactivate the cell cycle machinery and retinogenic factors to necessary levels might be key barriers blocking Müller cells from entering an RPC-like regeneration state. DNA methylation might regulate the expression of a subset of Müller cell-specific functional genes during development but is likely not involved in restricting the regeneration activity of Müller cells.


Assuntos
Senescência Celular/fisiologia , Células Ependimogliais/metabolismo , Traumatismos Oculares/metabolismo , Neuroglia/metabolismo , Retina/lesões , Transcriptoma/genética , Animais , Ilhas de CpG/genética , Metilação de DNA , Citometria de Fluxo , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , Regeneração/fisiologia , Células-Tronco/metabolismo
3.
Results Probl Cell Differ ; 68: 419-454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598866

RESUMO

Regeneration has fascinated both scientists and non-scientists for centuries. Many organisms can regenerate, and arthropod limbs are no exception although their ability to regenerate is a product shaped by natural and sexual selection. Recent studies have begun to uncover cellular and molecular processes underlying limb regeneration in several arthropod species. Here we argue that an evo-devo approach to the study of arthropod limb regeneration is needed to understand aspects of limb regeneration that are conserved and divergent. In particular, we argue that limbs of different species are comprised of cells at distinct stages of differentiation at the time of limb loss and therefore provide insights into regeneration involving both stem cell-like cells/precursor cells and differentiated cells. In addition, we review recent studies that demonstrate how limb regeneration impacts the development of the whole organism and argue that studies on the link between local tissue damage and the rest of the body should provide insights into the integrative nature of development. Molecular studies on limb regeneration are only beginning to take off, but comparative studies on the mechanisms of limb regeneration across various taxa should not only yield interesting insights into development but also answer how this remarkable ability evolved across arthropods and beyond.


Assuntos
Artrópodes/citologia , Artrópodes/fisiologia , Evolução Biológica , Extremidades/fisiologia , Regeneração/fisiologia , Animais , Diferenciação Celular
4.
Nat Commun ; 10(1): 4365, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554796

RESUMO

Epithelia are exposed to diverse types of stress and damage from pathogens and the environment, and respond by regenerating. Yet, the proximal mechanisms that sense epithelial damage remain poorly understood. Here we report that p38 signaling is activated in adult Drosophila midgut enterocytes in response to diverse stresses including pathogenic bacterial infection and chemical and mechanical insult. Two upstream kinases, Ask1 and Licorne (MKK3), are required for p38 activation following infection, oxidative stress, detergent exposure and wounding. Ask1-p38 signaling in enterocytes is required upon infection to promote full intestinal stem cell (ISC) activation and regeneration, partly through Upd3/Jak-Stat signaling. Furthermore, reactive oxygen species (ROS) produced by the NADPH oxidase Nox in enterocytes, are required for p38 activation in enterocytes following infection or wounding, and for ISC activation upon infection or detergent exposure. We propose that Nox-ROS-Ask1-MKK3-p38 signaling in enterocytes integrates multiple different stresses to induce regeneration.


Assuntos
Proteínas de Drosophila/metabolismo , Intestinos/fisiopatologia , MAP Quinase Quinase 3/metabolismo , MAP Quinase Quinase Quinases/metabolismo , NADPH Oxidases/metabolismo , Regeneração/fisiologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Animais Geneticamente Modificados , Infecções Bacterianas/microbiologia , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Enterócitos/metabolismo , Enterócitos/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiopatologia , Intestinos/microbiologia , Intestinos/patologia , MAP Quinase Quinase 3/genética , MAP Quinase Quinase Quinases/genética , NADPH Oxidases/genética , Estresse Oxidativo , Regeneração/genética , Células-Tronco/metabolismo , Células-Tronco/microbiologia , Estresse Mecânico , Proteínas Quinases p38 Ativadas por Mitógeno/genética
5.
Nat Commun ; 10(1): 4368, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554819

RESUMO

The colonic epithelial turnover is driven by crypt-base stem cells that express the R-spondin receptor Lgr5. Signals that regulate epithelial regeneration upon stem cell injury are largely unknown. Here, we explore the dynamics of Wnt signaling in the colon. We identify two populations of cells with active Wnt signaling: highly proliferative Lgr5+/Axin2+ cells, as well as secretory Lgr5-/Axin2+ cells. Upon Lgr5+ cell depletion, these cells are recruited to contribute to crypt regeneration. Chemical injury induced by DSS leads to a loss of both Lgr5+ cells and Axin2+ cells and epithelial regeneration is driven by Axin2- cells, including differentiated Krt20+ surface enterocytes. Regeneration requires stromal Rspo3, which is present at increased levels upon injury and reprograms Lgr5- but Lgr4+ differentiated cells. In contrast, depletion of stromal Rspo3 impairs crypt regeneration, even upon mild injury. We demonstrate that Rspo3 is essential for epithelial repair via induction of Wnt signaling in differentiated cells.


Assuntos
Colo/fisiologia , Mucosa Intestinal/fisiologia , Regeneração/fisiologia , Células-Tronco/metabolismo , Trombospondinas/metabolismo , Animais , Proteína Axina/genética , Proteína Axina/metabolismo , Diferenciação Celular/genética , Colite/genética , Colite/metabolismo , Colo/metabolismo , Enterócitos/metabolismo , Perfilação da Expressão Gênica/métodos , Mucosa Intestinal/metabolismo , Queratina-20/genética , Queratina-20/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo , Regeneração/genética , Células-Tronco/citologia , Trombospondinas/genética , Via de Sinalização Wnt/genética
6.
Nat Commun ; 10(1): 4402, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562306

RESUMO

T lymphocytes must be produced throughout life, yet the thymus, where T lymphocytes are made, exhibits accelerated atrophy with age. Even in advanced atrophy, however, the thymus remains plastic, and can be regenerated by appropriate stimuli. Logically, thymic atrophy is thought to reflect senescent cell death, while regeneration requires proliferation of stem or progenitor cells, although evidence is scarce. Here we use conditional reporters to show that accelerated thymic atrophy reflects contraction of complex cell projections unique to cortical epithelial cells, while regeneration requires their regrowth. Both atrophy and regeneration are independent of changes in epithelial cell number, suggesting that the size of the thymus is regulated primarily by rate-limiting morphological changes in cortical stroma, rather than by their cell death or proliferation. Our data also suggest that cortical epithelial morphology is under the control of medullary stromal signals, revealing a previously unrecognized endocrine-paracrine signaling axis in the thymus.


Assuntos
Células Epiteliais/metabolismo , Regeneração/genética , Células Estromais/metabolismo , Linfócitos T/metabolismo , Timo/metabolismo , Animais , Atrofia/genética , Atrofia/metabolismo , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microscopia Confocal , Tamanho do Órgão/genética , Regeneração/fisiologia , Timo/patologia , Timo/fisiopatologia
7.
Ecotoxicol Environ Saf ; 185: 109680, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31546204

RESUMO

The freshwater planarian mostly lives in the upper reaches of springs and rivers. Generally, it is realized as a suitable warning indicator of environmental toxicants. The freshwater planarian Dugesia japonica has a powerful regenerative capability and can regenerate a new individual including a complete central nervous system in one week. Rapamycin is an inhibitor of mammalian TORC1 (target of rapamycin complex-1) and used in the treatment of some diseases like cancer, cardiovascular and neurological diseases. However, the roles of rapamycin in the regulation of planarian regeneration remain to be elucidated. In present study, freshwater planarians D. japonica were firstly treated with 1 µM rapamycin for 18 h exposures and the expression patterns of Djtor was analyzed by the whole-mount in situ hybridization (WISH). Our results indicated rapamycin could strongly inhibit Djtor expression in planarian D. japonica and cause asymmetric blastemas and neuronal defects in planarians. Furthermore, knockdown of Djtor gene in planarians using RNA interference resulted in the suppression of downstream autophagy genes. These findings suggested that rapamycin might regulate freshwater planarian regeneration via Djtor signaling pathway.


Assuntos
Planárias/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Sirolimo/toxicidade , Serina-Treonina Quinases TOR/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Sistema Nervoso Central/efeitos dos fármacos , Neurônios , Planárias/genética , Planárias/crescimento & desenvolvimento , Planárias/metabolismo , Interferência de RNA , Regeneração/fisiologia , Transdução de Sinais , Serina-Treonina Quinases TOR/genética
8.
Tissue Cell ; 59: 1-9, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383283

RESUMO

The effect of the GM6001 metalloproteinase inhibitor on the regeneration of ambulacral structures in Eupentacta fraudatrix has been investigated. Inhibition of proteinase activity exerts a marked effect on regeneration, being dependent on the time when GM6001 is injected. When administration of the inhibitor begins on day 3 post-injury, regeneration is completely abolished, and the animals die. This means that early activation of proteinases is crucial for triggering the regenerative process in holothurians. When GM6001 in first injected on day 7 post-injury, the regeneration rate decreases. However, this effect has proven to be reversible: when inhibition ceases, the regeneration resumes. The effect of the inhibitor is manifested as a retarded degradation of the extracellular matrix, the lack of cell dedifferentiation, and, probably, a slower cell migration. The gelatinase activity is detected in all the regenerating organs of E. fraudatrix. In the holothurian Cucumaria japonica, which is not capable of healing skin wounds and ambulacrum reparation, no gelatinase activity was observed at the site of damage. A suggestion is made that proteinases play an important role in regeneration in holothurians. The most probable morphogenesis regulators are matrix metalloproteinases with gelatinase activity.


Assuntos
Dipeptídeos/farmacologia , Gelatinases/antagonistas & inibidores , Holothuria/fisiologia , Inibidores de Metaloproteinases de Matriz/farmacologia , Regeneração/efeitos dos fármacos , Animais , Gelatinases/metabolismo , Regeneração/fisiologia
9.
Cell Prolif ; 52(6): e12672, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31441162

RESUMO

OBJECTIVES: Application of non-invasive imaging methods plays an important role in the assessment of cellular therapy effects in peripheral artery disease. The purpose of this work was to evaluate the kinetics of MRI-derived parameters characterizing ischaemic hindlimb muscle after administration of human mesenchymal stromal cells derived from adipose tissue (hADSC) in mice. MATERIALS AND METHODS: MRI experiments were performed on a 9.4T Bruker system. The measurement protocol included transverse relaxation time mapping and diffusion tensor imaging. The monitoring period encompassed 14 days after femoral artery ligation and subsequent cell administration. The effect of hADSC transplantation was compared with the effect of normal human dermal fibroblasts (NHDFs) and phosphate-buffered saline injection. RESULTS: The most significant differences between the hADSC group and the remaining ones were observed around day 3 after ischaemia induction (increased transverse relaxation time in the hADSC group in comparison with the control group) and around day 7 (increased transverse relaxation time and decreased third eigenvalue of the diffusion tensor in the hADSC group in comparison with the control and NHDF groups) at the site of hADSC injection. Histologically, it was associated with increased macrophage infiltration at days 3-7 and with the presence of small regenerating fibres in the ischaemic tissue at day 7. CONCLUSIONS: Our results underscore the important role of macrophages in mediating the therapeutic effects of hADSCs and confirm the huge potential of magnetic resonance imaging in monitoring of cellular therapy effects.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular/fisiologia , Isquemia/patologia , Células-Tronco Mesenquimais/citologia , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Imagem de Tensor de Difusão/métodos , Fibroblastos/patologia , Humanos , Masculino , Camundongos Transgênicos , Neovascularização Fisiológica/fisiologia , Regeneração/efeitos dos fármacos , Regeneração/fisiologia
10.
Gene ; 717: 144047, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31421190

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling pathways play important roles in the formation of the blood vascular system and nervous system across animal phyla. We have earlier reported VEGF and FGF from Hydra vulgaris Ind-Pune, a cnidarian with a defined body axis, an organized nervous system and a remarkable ability of regeneration. We have now identified three more components of VEGF and FGF signaling pathways from hydra. These include FGF-1, FGF receptor 1 (FGFR-1) and VEGF receptor 2 (VEGFR-2) with a view to deciphering their possible roles in regeneration. METHODS: In silico analysis of proteins was performed using Clustal omega, Swiss model, MEGA 7.0, etc. Gene expression was studied by whole mount in situ hybridization. VEGF and FGF signaling was inhibited using specific pharmacological inhibitors and their effects on head regeneration were studied. RESULTS: Expression patterns of the genes indicate a possible interaction between FGF-1 and FGFR-1 and also VEGF and VEGFR-2. Upon treatment of decapitated hydra with pharmacological inhibitor of FGFR-1 or VEGFR-2 for 48 h, head regeneration was delayed in treated as compared to untreated, control regenerates. When we studied the expression of head specific genes HyBra1 and HyKs1 and tentacle specific gene HyAlx in control and treated regenerates using whole mount in situ hybridization, expression of all the three genes was found to be adversely affected in treated regenerates. CONCLUSIONS: The results suggest that VEGF and FGF signaling play important roles in regeneration of hypostome and tentacles in hydra.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Cabeça/fisiologia , Hydra/fisiologia , Regeneração/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Simulação por Computador , Fator 1 de Crescimento de Fibroblastos/química , Fator 1 de Crescimento de Fibroblastos/genética , Fator 1 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Hydra/efeitos dos fármacos , Indóis/farmacologia , Domínios Proteicos , Pirróis/farmacologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/química , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Regeneração/efeitos dos fármacos , Transdução de Sinais , Homologia Estrutural de Proteína , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Int J Oral Sci ; 11(3): 23, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31423011

RESUMO

In modern medicine, bone and dental loss and defects are common and widespread morbidities, for which regenerative therapy has shown great promise. Mesenchymal stem cells, obtained from various sources and playing an essential role in organ development and postnatal repair, have exhibited enormous potential for regenerating bone and dental tissue. Currently, mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering. Nevertheless, the efficacy of MSC-based regeneration is not always fulfilled, especially in diseased microenvironments. Specifically, the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs, both as donors and recipients. Accordingly, approaches targeting a diseased microenvironment have been established, including improving the diseased niche to restore endogenous MSCs, enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies. Moreover, the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy. In this review, we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment, emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Regeneração/fisiologia , Engenharia Tecidual/métodos , Regeneração Óssea , Osso e Ossos , Humanos
12.
Biomed Pharmacother ; 117: 109191, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387187

RESUMO

Normal wound repair is a dynamic and complex process involving multiple coordinated interactions between growth factors, cytokines, chemokines, and various cells. Any failure during the repair process may cause chronic wounds or scar formation, which increase the financial burden of patients due to repetitive treatments and considerable medical expenditures, and affect their quality of life. Nowadays, extensive efforts have been made to develop novel therapeutics for wound repair. Genetic engineering technology, tissue engineering technology, stem cell-based therapy, physical and biochemical technology, and vacuum-assisted closure technique have been proposed to be beneficial for wound repair, and shown considerable potential for improving the rate and quality of wound healing and skin regeneration. However, challenges remain as applying these techniques. As the development of cell biology and molecular biology, the understanding of the mechanism under wound repair has gradually deepened. As the growth of interdisciplinary research on physics, chemistry, biology, tissue engineering, and materials, the concept and technique relating wound repair for clinical application have rapidly developed. This article reviews the latest progress on the mechanism and technique in wound repair.


Assuntos
Cicatrização/fisiologia , Animais , Cicatriz/metabolismo , Cicatriz/terapia , Citocinas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Qualidade de Vida , Regeneração/fisiologia , Pele/metabolismo , Pele/fisiopatologia , Engenharia Tecidual/métodos
13.
Environ Sci Pollut Res Int ; 26(26): 27435-27443, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327142

RESUMO

Production, distribution, and disposal of pharmaceutical products, including beta-blockers, have become a global issue. Beta-blockers are known to persist in the environment months after their release and may result in the disruption of the homeostatic system in non-target organisms. Here, we study the bioconcentration of three of the most commonly used beta-blockers and their effect on the regeneration of Girardia dorotocephala, a freshwater brown planarian. Acute toxicity tests determined LC50s for acebutolol, metoprolol, and propranolol to be 778 mg/L, 711 mg/L, and 111 mg/L, respectively. The quantification and analysis of beta-blocker bioconcentration during acute exposure were performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After 4 days of exposure to beta-blockers, the bioconcentration drastically decreased for all three beta-blockers at all exposure levels, suggesting that an effective mechanism to reduce uptake or excrete beta-blockers could be present. Additionally, Girardia dorotocephala were cut proximal to the head and the quality of regeneration was documented from each fragment daily. No significant difference was visually observed after 2 weeks of regeneration between the brown planarians placed in beta-blocker solution and those placed in control solution.


Assuntos
Antagonistas Adrenérgicos beta/toxicidade , Planárias/efeitos dos fármacos , Planárias/fisiologia , Regeneração/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Antagonistas Adrenérgicos beta/farmacocinética , Animais , Cromatografia Líquida , Ecotoxicologia/métodos , Dose Letal Mediana , Regeneração/fisiologia , Espectrometria de Massas em Tandem , Testes de Toxicidade Aguda , Poluentes Químicos da Água/farmacocinética
14.
Pediatr Cardiol ; 40(7): 1345-1358, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31346664

RESUMO

The neonatal capacity for cardiac regeneration in mice is well studied and has been used to develop many potential strategies for adult cardiac regenerative repair following injury. However, translating these findings from rodents to designing regenerative therapeutics for adult human heart disease remains elusive. Large mammals including pigs, dogs, and sheep are widely used as animal models of humans in preclinical trials of new cardiac drugs and devices. However, very little is known about the fundamental cardiac cell biology and the timing of postnatal cardiac events that influence cardiomyocyte proliferation in these animals. There is emerging evidence that external physiological and environmental cues could be the key to understanding cardiomyocyte proliferative behavior. In this review, we survey available literature on postnatal development in various large mammal models to offer a perspective on the physiological and cellular characteristics that could be regulating cardiomyocyte proliferation. Similarities and differences between developmental milestones, cardiomyocyte maturational events, as well as environmental cues regulating cardiac development, are discussed for various large mammals, with a focus on postnatal cardiac regenerative potential and translatability to the human heart.


Assuntos
Proliferação de Células/fisiologia , Coração/fisiologia , Regeneração/fisiologia , Animais , Modelos Animais de Doenças , Cães , Humanos , Miócitos Cardíacos/fisiologia , Ovinos , Suínos
15.
Med Sci (Paris) ; 35(6-7): 549-555, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31274085

RESUMO

The study of gut diseases is often limited by the access to human biological tissues and animal models that do not faithfully mimic the human pathologies. In this context, the development of intestinal organoids from human pluripotent stem cells is paving the way of gastrointestinal physiology and digestive disease study. In this review, we recall the embryonic development of the digestive tract and its translation to human pluripotent stem cell differentiation. We also present the different types of intestinal organoids that can be generated, as well as their applications in research.


Assuntos
Intestinos/citologia , Organoides/citologia , Células-Tronco Pluripotentes/citologia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos/métodos , Gastroenteropatias/patologia , Gastroenteropatias/terapia , Trato Gastrointestinal/citologia , Trato Gastrointestinal/crescimento & desenvolvimento , Trato Gastrointestinal/fisiologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Intestinos/fisiologia , Organoides/fisiologia , Células-Tronco Pluripotentes/fisiologia , Regeneração/fisiologia , Técnicas de Cultura de Tecidos
16.
PLoS Biol ; 17(7): e3000326, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31260439

RESUMO

Sensory hair cells are mechanoreceptors required for hearing and balance functions. From embryonic development, hair cells acquire apical stereociliary bundles for mechanosensation, basolateral ion channels that shape receptor potential, and synaptic contacts for conveying information centrally. These key maturation steps are sequential and presumed coupled; however, whether hair cells emerging postnatally mature similarly is unknown. Here, we show that in vivo postnatally generated and regenerated hair cells in the utricle, a vestibular organ detecting linear acceleration, acquired some mature somatic features but hair bundles appeared nonfunctional and short. The utricle consists of two hair cell subtypes with distinct morphological, electrophysiological and synaptic features. In both the undamaged and damaged utricle, fate-mapping and electrophysiology experiments showed that Plp1+ supporting cells took on type II hair cell properties based on molecular markers, basolateral conductances and synaptic properties yet stereociliary bundles were absent, or small and nonfunctional. By contrast, Lgr5+ supporting cells regenerated hair cells with type I and II properties, representing a distinct hair cell precursor subtype. Lastly, direct physiological measurements showed that utricular function abolished by damage was partially regained during regeneration. Together, our data reveal a previously unrecognized aberrant maturation program for hair cells generated and regenerated postnatally and may have broad implications for inner ear regenerative therapies.


Assuntos
Diferenciação Celular/fisiologia , Células Ciliadas Auditivas/fisiologia , Células Ciliadas Vestibulares/fisiologia , Mecanorreceptores/fisiologia , Regeneração/fisiologia , Sáculo e Utrículo/fisiologia , Animais , Fenômenos Eletrofisiológicos/fisiologia , Células Ciliadas Auditivas/citologia , Células Ciliadas Vestibulares/citologia , Mecanorreceptores/citologia , Camundongos Transgênicos , Sáculo e Utrículo/citologia , Transmissão Sináptica/fisiologia
17.
BMC Res Notes ; 12(1): 425, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311592

RESUMO

OBJECTIVE: Passion fruit improvement efforts by conventional breeding have had limited success calling for research into alternative approaches such as tissue culture and genetic engineering. An efficient and reproducible regeneration system is a prerequisite for successful genetic engineering. Currently, there is no reliable regeneration system for Uganda's passion fruit varieties owing to the high heterogeneity of the Passiflora genus. Therefore, this study aimed at establishing an efficient and reproducible regeneration system for Uganda's Passiflora edulis f. flavicarpa (yellow passion fruit) and Passiflora edulis f. edulis (purple passion fruit) for routine utilization with an ultimate goal of improving its agronomic value. RESULTS: The study successfully induced shoots by both direct and indirect organogenesis for the yellow passion fruit variety. Highest shoot induction frequency (14.85%) was achieved on 8.9 µM BAP while 7.9 µM BAP did not initiate any shoots. Optimal shoot elongation and rooting was achieved on 0.44 µM BAP and 5.37 µM α-naphthaleneacetic (NAA) respectively. Rooted yellow passion fruit plantlets were successfully weaned with over 65% survival rates. It took approximately 6 months to produce a weaned healthy passion fruit plant. The purple passion fruit variety proved to be recalcitrant to tissue culture with no successful shoot or callus induction.


Assuntos
Engenharia Genética/métodos , Passiflora/fisiologia , Folhas de Planta/fisiologia , Regeneração/fisiologia , Técnicas de Cultura de Tecidos/métodos , Ácidos Naftalenoacéticos/farmacologia , Organogênese/efeitos dos fármacos , Organogênese/genética , Passiflora/classificação , Passiflora/genética , Folhas de Planta/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Regeneração/genética , Especificidade da Espécie , Uganda
18.
Cells ; 8(6)2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167434

RESUMO

Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region.


Assuntos
Cemento Dentário/fisiologia , Ligamento Periodontal/fisiologia , Regeneração/fisiologia , Células-Tronco/metabolismo , Terapia Genética , Humanos , Periodontite/patologia , Periodontite/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Engenharia Tecidual , Tecidos Suporte/química
19.
Medicine (Baltimore) ; 98(23): e15864, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169690

RESUMO

RATIONALE: Degloving injury of the upper limb often extends to underlying tendons and bone, which is at high risk of treatment failure if only simple reattachment of defatted avulsed skins was performed. Pelnac dermal regeneration template could be used as a treatment choice for necrosis of the reattached avulsed skins in a degloving injury. PATIENT CONCERNS: A 48-year-old woman with a degloving injury of the right forearm, wrist, and hand received initial treatment by reattachment of the defatted avulsed skins over the wound bed. However, 17 days postoperatively, the reattached skins developed complete necrosis, leaving large size of tissue defects and tendon/bone exposure. DIAGNOSIS: Failure to reconstruct the skin and soft-tissue envelop by reattachment of the defatted avulsed skins in a severe degloving injury of the upper limb. INTERVENTIONS: We decided to use a 2-stage procedure of Pelnac dermal regeneration template and secondary skin graft to solve this issue, in consideration of these conditions and the patient' demanding of limb function and aesthetic appearance. OUTCOMES: At the final follow-up, this patient obtained an excellent result, in term of scar quality, aesthetic appearance, and the ability to perform the daily activities. LESSONS: We believe this could become an interesting option in patients who needed revision procedure for management of complex wounds with tendon/bone exposure following the necrosis of reattached skins in degloving injuries.


Assuntos
Desenluvamentos Cutâneos/cirurgia , Derme/fisiologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Regeneração/fisiologia , Tecidos Suporte , Bandagens , Desbridamento , Drenagem , Feminino , Humanos , Pessoa de Meia-Idade , Necrose , Transplante de Pele/efeitos adversos , Transplante de Pele/métodos , Cicatrização/fisiologia
20.
Nat Commun ; 10(1): 2811, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243280

RESUMO

How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.


Assuntos
Folículo Piloso/fisiologia , RNA de Cadeia Dupla/fisiologia , Regeneração/fisiologia , Receptor 3 Toll-Like/metabolismo , Tretinoína/metabolismo , Animais , Benzoatos/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Humanos , Interleucina-6/administração & dosagem , Interleucina-6/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Interferência de RNA , RNA Interferente Pequeno , Estilbenos/farmacologia , Cicatrização
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