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1.
Science ; 368(6498): 1428-1429, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32587008
3.
Artigo em Inglês | MEDLINE | ID: mdl-32559029

RESUMO

This in vivo study assessed the effect of mineral trioxide aggregate (MTA) as a matrix carrier for recombinant human platelet-derived growth factor (rhPDGF) and enamel matrix protein (EMP) on pulp tissue healing following pulp capping. Eighteen intact human premolars scheduled for extraction were included. Coronal access and pulpotomy were performed, and each tooth was left exposed to the oral cavity for 1 hour before pulp capping was performed. Teeth were randomly assigned to one of the following pulp-capping groups (n = 6 each): Group 1 (MTA only); Group 2 (MTA+EMP); or Group 3 (MTA+rhPDGF). Coronal access cavities were then sealed. Immediate preoperative, postoperative, and 4-month follow-up radiographs were taken. At 4 months, the teeth were extracted atraumatically, and histomorphometric and micro-computed tomography (µCT) analyses were performed. Group 1 showed a thin, uneven, irregular dentin-like structure. Its average thickness was 0.3 ± 0.084 mm measured histologically and 0.29 ± 0.091 mm measured by µCT. Group 2 showed of a nonporous, even-thickness dentin-like structure with multiple root-canal obliterations. Highly dense, atubular dentin-like structures associated with presence of odontoblastic lacunae were seen. The structure's average thickness was 0.87 ± 0.09 mm (histologically) and 0.81 ± 0.17 mm (µCT). Group 3 showed a thick and complete 3D continuous seal of newly formed dentin-like structure covering the pulpal space. It resembled secondary dentin in form, porosity, and tubular structural organization, and its average thickness was 0.94 ± 0.02 mm (histologically) and 0.91 ± 0.09 mm (µCT). Groups 2 and 3 showed higher amounts of newly formed dentin-like structure, that was also thicker, than Group 1 (P < .05). No statistically significant differences in structure thickness were found between Groups 2 and 3. The nature of the structure can differ if rhPDGF or EMP is added to MTA for pulp-capping purposes. Combination of rhPDGF and MTA resulted in a newly formed structure resembling secondary dentin, whereas a combination of EMP and MTA produced a nonporous, highly dense dentinal-like structure associated with significant root-canal obliterations.


Assuntos
Capeamento da Polpa Dentária , Dentina Secundária , Timidina Fosforilase , Compostos de Alumínio , Compostos de Cálcio , Polpa Dentária , Combinação de Medicamentos , Humanos , Óxidos , Regeneração , Silicatos , Microtomografia por Raio-X
4.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(3): 240-244, 2020 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-32573128

RESUMO

OBJECTIVE: This study aimed to compare the cartilage regeneration of the stromal vascular fraction (SVF) cells and adipose-derived mesenchymal stem cells (ASCs) cocultured with chondrocytes seeded on the scaffolds. METHODS: The cellular morphologies and proliferation capabilities on the scaffolds were evaluated. The scaffolds with the cocul-ture of ASCs/SVF and chondrocytes were implanted into the full thickness cartilage defective rabbit joints for 10 weeks. RESULTS: The cells seeded into the scaffolds showed good adhesion and proliferation. Implantation with SVF and chondrocytes revealed desirable in vitro healing outcomes. CONCLUSIONS: The SVF cells were better than ASCs in terms of the formation of cartilage matrix in a coimplantation model. Without in vitro expansion, the SVF cells are good cell sources for cartilage repair.


Assuntos
Cartilagem , Condrócitos , Tecido Adiposo , Animais , Técnicas de Cocultura , Coelhos , Regeneração
5.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(3): 314-318, 2020 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-32573141

RESUMO

Tubular dentin is of great significance in the process of tooth tissue and tooth regeneration, because it is not only the structural feature of primary dentin, but also can affect the tooth sensory function, affect the differentiation of dental pulp cells and provide strong mechanical support for teeth. Scaffold is one of the three elements of tissue engineering dentin regeneration. Most experiments on dentin regeneration involve the study of the microstructure and mechanical properties of the scaffold. The microstructure and mechanical characteristics of scaffold materials have important effects on the differentiation and adhesion of odontoblast, it can directly affect the tissue structure of regenerated dentin.


Assuntos
Polpa Dentária , Tecidos Suporte , Diferenciação Celular , Dentina , Odontoblastos , Regeneração , Engenharia Tecidual
6.
Int J Periodontics Restorative Dent ; 40(4): e137-e146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559031

RESUMO

Furcation involvement (FI) is one of the most detrimental factors affecting tooth survival rate over time. Several authors have used the severity of FI for assessing the prognosis of the tooth and the complexity of periodontal disease. While many approaches have been shown to improve the prognosis of furcation-involved teeth, clinical guidelines recommending one treatment or another (based on the horizontal and vertical component of the furcation defects) have not yet been proposed. To this aim, the present article introduces recommendations for the treatment of molars with FI and discusses different treatment options with their potential regenerative approaches. Patient-related factors, together with hard and soft-tissue conditions that may affect the outcomes of periodontal regeneration, are discussed.


Assuntos
Defeitos da Furca/cirurgia , Dente , Regeneração Tecidual Guiada Periodontal , Humanos , Dente Molar/cirurgia , Regeneração
7.
Chin J Dent Res ; 23(2): 143-150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32548605

RESUMO

OBJECTIVE: To compare the biological characteristics of dental pulp stem cells (DPSCs) and inflamed dental pulp derived stem cells (I-DPSCs) in vitro and their regeneration potential in Beagle immature premolars. METHODS: Pulpitis was induced in the premolars of one beagle dog by opening the pulp chamber for 2 weeks, and inflammation was histologically confirmed. DPSCs and I-DPSCs were isolated from normal and inflamed dental pulp, and cell morphology, expression of mesenchymal stem cell markers, clone formation ability, cell proliferation and osteogenic/odontogenic differentiation potential were compared. The dental pulp of 20 roots from 10 immature premolars was extracted and divided into two groups. DPSCs or I-DPSCs with scaffolds were transplanted into the root canals. The roots were extracted after 3 months, and pulp regeneration was evaluated by histological analysis. The data were statistically analysed using one-way ANOVA and a Student t test. RESULTS: Histological analyses showed lymphocyte infiltration and elevated TNF-α expression, which confirmed the diagnosis of pulpitis. I-DPSCs showed similar morphology, marker gene expression and clone formation ability but greater proliferation ability and osteogenic/odontogenic differentiation potential. Pulp-like tissue formation and bone- and dentine-like tissue deposition were observed in both DPSC- and I-DPSC-transplanted roots. CONCLUSION: DPSCs derived from inflammatory dental pulp tissue have similar biological characteristics to those from normal dental pulp and could mediate pulp and dentine regeneration in immature premolars.


Assuntos
Polpa Dentária , Regeneração , Animais , Dente Pré-Molar , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Cães , Humanos , Células-Tronco
8.
Life Sci ; 255: 117763, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32389831

RESUMO

AIMS: To explored the potential of human umbilical cord mesenchymal stem cells (hUCMSCs) as seed cells for dental pulp regeneration and the possibility of cotransplantation hUCMSCs and endothelial cells (ECs) for angiogenesis and pulp regeneration in vivo. MATERIALS AND METHODS: hUCMSCs and human umbilical vein endothelial cells (HUVECs) were cocultured for matrigel angiogenesis assay in vitro and Matrigel plug assay in vivo. Next, we used the transwell coculture system to coculture hUCMSCs and HUVECs in vitro for RNA- sequencing (RNA-seq). Last, encapsulated hUCMSCs and HUVECs in scaffolds were injected into the root segments, and transplanted into immunodeficient mice for dental pulp regeneration. KEY FINDINGS: In vitro Matrigel angiogenesis assay and in vivo Matrigel plug assay indicated that cocultured hUCMSCs and HUVECs promote vascular formation of HUVECs, especially in 1:5 (hUCMSCs:HUVECs) coculture group. The RNA-seq result indicated that cocultured HUVECs exhibited high Hif-1 signaling pathway activity. We performed the cell transfection assay to knock down HIF1A-AS2 in HUVECs and then coculture with hUCMSCs, and the expression of VEGFA, HIF1A and PECAM1 were reduced. In pulp regeneration assay, Cotransplantation of hUCMSCs and HUVECs (1,5) group showed pulp-like tissue regeneration. SIGNIFICANCE: Cocultured hUCMSCs and HUVECs can promote vascular formation of HUVECs, and the optimal coculture ration is 1:5 (hUCMSCs:HUVECs). hUCMSCs promote angiogenesis of HUVECs through the long noncoding RNA HIF1A-AS2-activation of the Hif-1 signaling pathway. Cotransplantation of hUCMSCs and HUVECs can regenerate dental pulp-like tissue in vivo.


Assuntos
Polpa Dentária/metabolismo , Células Endoteliais da Veia Umbilical Humana/transplante , Transplante de Células-Tronco Mesenquimais/métodos , Neovascularização Fisiológica/fisiologia , Animais , Técnicas de Cocultura , Colágeno/metabolismo , Polpa Dentária/citologia , Combinação de Medicamentos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Fator 1 Induzível por Hipóxia/metabolismo , Laminina/metabolismo , Camundongos , Proteoglicanas/metabolismo , RNA Longo não Codificante/genética , Regeneração/fisiologia , Cordão Umbilical/citologia
9.
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
10.
J Oral Sci ; 62(2): 222-225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224573

RESUMO

The present study was done to develop a useful experimental model for analysis of the effects of physiologically active substances on atrophy and regeneration of salivary gland acinar cells. Resection wounds (diameter, 3 mm) were made in the submandibular glands of 8-week-old Wistar rats (n = 24) for histochemical examination on Days 3, 5, 7, 10, 14, and 21 after implantation of a gelatin-based hydrogel sheet. The results showed that the sheet had nearly disappeared by Day 10. Regions around the resection wounds were classified as normal, atrophic, or necrotic. In atrophic regions, acinar cells atrophied after resection, and few acinar cells were observed on Day 7. On Days 5-7, striated and granular ducts resembled duct-like structures. On Day 10, newly formed acinar cells were confirmed by increased periodic acid-Schiff staining, and a greater number of mature cells was present thereafter. In necrotic regions, acinar and ductal cells were destroyed, and scattered enucleated acinar cells and duct-like structures were present, on Day 3; newly formed acinar cells were observed on Day 10. Thus, the experimental model demonstrated atrophy and regeneration of the submandibular gland and enabled analysis of the effects of sustained release of physiologically active substances contained within an implanted sheet.


Assuntos
Gelatina , Glândula Submandibular , Animais , Hidrogéis , Ratos , Ratos Wistar , Regeneração , Ductos Salivares , Cicatrização
11.
Gene ; 743: 144624, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32224274

RESUMO

The giant ciliate Stentor coeruleus (S. coeruleus) is a suitable model organism for studying morphogenesis and regeneration at the single-cell level. It contains a prominent structure on the anterior end of the cell, known as the oral apparatus (OA). OA can be induced to shed by urea treatment and then new OA regenerates via a series of defined morphological events and the cell resumes normal feeding activity. We identified OA constituents in S. coeruleus by mass spectrometry. A total of 882 OA-associated proteins were identified; the homologs of 181 of these are known OA constituents in other organisms. The expression pattern of OA-associated genes during regeneration was investigated using single-cell transcriptome sequencing. The expression of most OA-associated genes was high during regeneration, indicating their stable expression after OA shedding. We also identified OA-associated differentially expressed genes that may be involved in regulating OA reconstruction. In summary, this study gives preliminary insight into the molecular basis of OA in S. coeruleus.


Assuntos
Cilióforos/fisiologia , Genes de Protozoários/genética , Proteínas de Protozoários/metabolismo , Regeneração , Espectrometria de Massas , Proteômica , Proteínas de Protozoários/genética , Análise de Sequência de RNA , Análise de Célula Única
12.
Adv Exp Med Biol ; 1229: 163-180, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32285411

RESUMO

Cardiovascular disease is a leading cause of death worldwide, and with the dramatically increasing numbers of heart failure patients in the next 10 years, mortality will only increase [1]. For patients with end-stage heart failure, heart transplantation is the sole option. Regrettably, the number of available donor hearts is drastically lower than the number of patients waiting for heart transplantation. Despite evidence of cardiomyocyte renewal in adult human hearts, regeneration of functional myocardium after injury can be neglected. The limited regenerative capacity due to inadequate proliferation of existing cardiomyocytes is insufficient to repopulate areas of lost myocardium [2]. As a solution, the hypothesis that adult stem cells could be employed to generate functional cardiomyocytes was proposed. One of the early studies that supported this hypothesis involved direct injection of hematopoietic c-kit-positive cells derived from bone marrow into the infarcted heart [3]. However, in sharp contrast, more recent evidence emerged demonstrating that these hematopoietic stem cells only differentiate into cells down the hematopoietic lineage rather than into cardiomyocytes [4, 5], and the focus shifted towards stem cells residing in the heart, called cardiac progenitor cells. These CPCs were extracted and injected into the myocardium to regenerate the heart [6]. In recent years, over 80 pre-clinical studies employing cardiac stem cells in vivo in large and small animals to evaluate the effect on functional parameters were systematically reviewed, identifying differences between large and small animals [7]. Despite the positive outcome of these stem cell therapies on functional parameters, c-kit-positive cardiac progenitor cells were shown to contribute minimally to the generation of functional cardiomyocytes [8, 9]. This heavily debated topic is summarized concisely by van Berlo and Molkentin [10]. Recently, single-cell sequencing and genetic lineage tracing of proliferative cells in the murine heart in both homeostatic and regenerating conditions did not yield a quiescent cardiac stem cell population or other cell types that support transdifferentiation into cardiomyocytes, nor did it support proliferation of cardiac myocytes [11, 12]. Now, the focus is shifting towards exploiting the limited regenerative capacity of the cardiomyocytes themselves, by re-activating proliferation of existing cardiomyocytes through dedifferentiation, reentry into the cell cycle, and cytokinesis. This process is the new focus of research to promote cardiac regeneration, and can be controlled on multiple levels, including cell-cycle manipulation, reprogramming, small molecules, extra-cellular matrix (ECM), proteins, and RNA regulation [13].


Assuntos
Miocárdio/citologia , Miócitos Cardíacos/citologia , RNA não Traduzido , Regeneração/genética , Animais , Diferenciação Celular , Humanos , Miócitos Cardíacos/transplante , Transplante de Células-Tronco
13.
Surg Technol Int ; 36: 41-47, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32243565

RESUMO

Skeletal muscle represents the largest mass of tissue in the body and is essential for motion and posture. Traumatic injury, tumor ablation, prolonged denervation or genetic defects lead to skeletal myopathies. The loss of muscle function or its regenerative properties often results in pain, deformity, and joint malfunction. The regenerative capacity of skeletal muscles depends on adult muscle stem cells, the so-called satellite cells; however, the population of these myogenic precursors, and thus their potential to restore large muscle tissue defects, is strongly limited. On the other hand, surgical treatment of skeletal muscle loss is hampered by the scarcity of functional replacement tissue. Only a few options currently exist to provide functional and aesthetic restoration of lost muscle tissues, other than free muscle flap transfer. While this reconstructive technique is a common practice, it involves the risk of significant donor-site morbidity. Therefore, alternative cells with the potential to regenerate muscle tissue need to be examined. Recently, many surgeons have studied the potential clinical application of mesenchymal stem cells (MSCs), which are an adult stem cell population that can undergo differentiation along the mesodermal lineage and secrete growth factors that can enhance tissue regeneration processes by promoting neovascularization. The regenerative potential of MSCs has been widely studied in vitro and in vivo in animal models. MSCs from adipose tissue as well as bone marrow have been shown to bear myogenic potential, which makes them ideal candidate stem cells for skeletal muscle tissue engineering applications. When compared to reconstructive procedures using autograft tissues, MSC therapy offers the potential of reducing or even eliminating donor-site morbidity. This review gives a comprehensive overview of the use of MSCs in in vitro muscle generation and in vivo muscle regeneration.


Assuntos
Células-Tronco Mesenquimais , Animais , Diferenciação Celular , Desenvolvimento Muscular , Músculo Esquelético , Regeneração , Engenharia Tecidual
14.
Int Endod J ; 53(7): 905-921, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32249441

RESUMO

AIM: To assess the outcomes of platelet-rich plasma as a scaffold in regenerative/revitalization endodontics (RET) using cone beam computed tomography (CBCT) and 2-dimensional radiographs. METHODOLOGY: Twenty-six healthy patients with mean age of 12.66 ± 4.47, and immature permanent anterior teeth with necrotic pulps, were randomly allocated to two groups, whereby RET was performed using platelet-rich plasma (PRP, test group) and blood clot (BLC, control group). Changes in root length (RL), root dentinal thickness (RDT), apical foramen width (AFW) and radiographic root area (RRA), were assessed using both radiographic methods, whilst changes in periapical area diameter (PAD) were assessed using CBCT, over a period of 12 months. T-test and chi-square/Fisher's exact tests were used to compare continuous and categorical data between BLC and PRP groups, respectively. Changes in RL, RDT, AFW, RRA and PAD were examined by comparing the two groups (PRP versus BLC) using multilevel modelling, considering the clustering effect of repeated measures of several teeth originating from the same participant. RESULTS: Changes in RL, RDT, AFW, RRA and PAD, over time, were found to be significant for both groups. There was, however, no difference between the RET techniques (PRP versus BLC), using both radiographic and CBCT methods. The results of both assessment techniques (CBCT and 2-dimensional radiographic methods) were highly consistent (overall ICC ranged between 0.80 and 0.94). In addition, a significant effect of baseline PAD was found on RL, RRA and AD at 12 months (RL effect = -0.68, P < 0.001; RRA effect = -1.91, P = 0.025; AD effect = 0.08, P = 0.024). CONCLUSION: The current study highlights successful and comparable clinical and radiographic outcomes of RET techniques using PRP and BLC. Standardized and calibrated 2-dimensional radiographic assessment was as effective as CBCT in assessing RET outcomes; therefore, the routine use of CBCT in RET is not recommended. Although an effect of baseline periapical lesion diameter on root development outcomes, at 12 months, were observed, more studies are recommended in order to assess such an effect.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Plasma Rico em Plaquetas , Necrose da Polpa Dentária , Dentição Permanente , Humanos , Regeneração
15.
Zhonghua Shao Shang Za Zhi ; 36(3): 161-165, 2020 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-32241040

RESUMO

Since the discovery of fibroblast growth factor (FGF) in the early 20th century, the multiple regulatory function of FGF has been found in development, metabolic regulation and tissue regeneration. Although FGF has the potential in wound healing of clinical practice, several technical bottlenecks occurred in the development of FGF drugs. Since 1992, our team has had many technical breakthroughs and developed some class Ⅰ new drugs of FGF and medical device. At the same time, we further investigated the network of metabolic regulation and signal transduction of FGF. All the efforts were for the purpose of the development of FGF new drugs and bringing benefit to patients.


Assuntos
Fatores de Crescimento de Fibroblastos/história , Regeneração/fisiologia , Transdução de Sinais , Cicatrização , Fator 1 de Crescimento de Fibroblastos , História do Século XX , Humanos
16.
Subcell Biochem ; 95: 87-117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32297297

RESUMO

This chapter brings together data on the role of retinoic acid (RA) in the embryonic development of fins in zebrafish , limbs in amphibians , chicks , and mice, and regeneration of the amphibian limb . The intention is to determine whether there is a common set of principles by which we can understand the mode of action of RA in both embryos and adults. What emerges from this synthesis is that there are indeed commonalities in the involvement of RA in processes that ventralize, posteriorize, and proximalize the developing and regenerating limb . Different axes of the limb have historically been studied independently; as for example, the embryonic development of the anteroposterior (AP) axis of the chick limb bud versus the regeneration of the limb bud proximodistal (PD) axis . But when we take a broader view, a unifying principle emerges that explains why RA administration to embryos and regenerating limbs results in the development of multiple limbs in both cases. As might be expected, different molecular pathways govern the development of different systems and model organisms, but despite these differences, the pathways involve similar RA signaling genes, such as tbx5, meis, shh, fgfs and hox genes. Studies of developing and regenerating systems have highlighted that RA acts by being synthesized in one embryonic location while acting in another one, exactly as embryonic morphogens do, although there is no evidence for the presence of an RA gradient within the limb . What also emerges is that there is a paucity of information on the involvement of RA in development of the dorsoventral (DV) axis . A molecular explanation as to how RA establishes and alters positional information in all three axes is the most important area of study for the future.


Assuntos
Extremidades/crescimento & desenvolvimento , Regeneração , Transdução de Sinais , Tretinoína/metabolismo , Animais
17.
Am J Physiol Heart Circ Physiol ; 318(4): H994-H1007, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32167779

RESUMO

The adult mammalian cardiomyocyte has a very limited capacity to reenter the cell cycle and advance into mitosis. Therefore, diseases characterized by lost contractile tissue usually evolve into myocardial remodeling and heart failure. Analyzing the cardiac transcriptome at different developmental stages in a large mammal closer to the human than laboratory rodents may serve to disclose positive and negative cardiomyocyte cell cycle regulators potentially targetable to induce cardiac regeneration in the clinical setting. Thus we aimed at characterizing the transcriptomic profiles of the early fetal, late fetal, and adult sheep heart by employing RNA-seq technique and bioinformatic analysis to detect protein-encoding genes that in some of the stages were turned off, turned on, or differentially expressed. Genes earlier proposed as positive cell cycle regulators such as cyclin A, cdk2, meis2, meis3, and PCNA showed higher expression in fetal hearts and lower in AH, as expected. In contrast, genes previously proposed as cell cycle inhibitors, such as meis1, p16, and sav1, tended to be higher in fetal than in adult hearts, suggesting that these genes are involved in cell processes other than cell cycle regulation. Additionally, we described Gene Ontology (GO) enrichment of different sets of genes. GO analysis revealed that differentially expressed gene sets were mainly associated with metabolic and cellular processes. The cell cycle-related genes fam64a, cdc20, and cdk1, and the metabolism-related genes pitx and adipoq showed strong differential expression between fetal and adult hearts, thus being potent candidates to be targeted in human cardiac regeneration strategies.NEW & NOTEWORTHY We characterized the transcriptomic profiles of the fetal and adult sheep hearts employing RNAseq technique and bioinformatic analyses to provide sets of transcripts whose variation in expression level may link them to a specific role in cell cycle regulation. It is important to remark that this study was performed in a large mammal closer to humans than laboratory rodents. In consequence, the results can be used for further translational studies in cardiac regeneration.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Coração/fisiologia , Miocárdio/metabolismo , Regeneração , Transcriptoma , Animais , Ciclina A/genética , Ciclina A/metabolismo , Feminino , Coração/crescimento & desenvolvimento , Masculino , Ovinos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Int J Nanomedicine ; 15: 1721-1730, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210562

RESUMO

Introduction: In this study, the combination of TEMPO-oxidized sacchachitin nanofibers (TOSCNFs) with chitosan-activated platelet-rich plasma (cPRP) was evaluated for remedying dry eye syndrome (DES). Methods: TOSCNFs, designated T050SC, were generated. T050SC combined with chitosan-activated (cPRP) was formulated as eye drops for application for severe DES. To evaluate the effects of cPRP and TOSCNFs on the repair of corneal injury, in vitro studies were conducted using Statens Seruminstitut rabbit corneal (SIRC) epithelial cells for cell proliferation and cell migration assays, and a severe DES animal model using rabbits was established with benzalkonium chloride (BAC) treatment for the evaluation. Results: Results showed that the optimal eye formulation contained PRP activated by 350 µg/mL of the low-molecular-weight chitosan group (L3) combined with 300 µg/mL TO50SC (L3+T050SC). In the WST-1 cell-proliferation assay, L3 and L3+TO50SC significantly increased Statens SIRC cell proliferation after 24 hrs of incubation. In the SIRC cell migration assay, the L3+TO50SC group showed a wound-healing efficiency of 89% after 24-hr treatment. After 5 days of treatment, Schirmer's test results did not simulate the dry eye animal model. Typical cornea appearance and eye fluorescein staining results showed that the L3 group had the best effect on improving cornea haze and epithelial damage. Conclusion: This study has determined that TOSCNFs effectively promoted the healing effect on severe cases of corneal damage, and also might enhance the clinical application and medical potential of PRP in ophthalmology.


Assuntos
Quitina/química , Óxidos N-Cíclicos/química , Síndromes do Olho Seco/terapia , Nanofibras/química , Plasma Rico em Plaquetas/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Quitina/farmacologia , Córnea/efeitos dos fármacos , Córnea/patologia , Córnea/cirurgia , Modelos Animais de Doenças , Síndromes do Olho Seco/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Fibroblastos/efeitos dos fármacos , Nanofibras/ultraestrutura , Oxirredução , Coelhos , Regeneração/efeitos dos fármacos
19.
Life Sci ; 250: 117582, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32222465

RESUMO

The ineffective immunosuppressant's and targeted strategies to neutralize inflammatory mediators have worsened the scenario of heart failure and have opened many questions for debate. Stem cell therapy has proven to be a promising approach for treating heart following myocardial infarction (MI). Adult stem cells, induced pluripotent stem cells and embryonic stem cells are possible cell types and have successfully shown to regenerate damaged myocardial tissue in pre-clinical and clinical studies. Current implications of using mesenchymal stem cells (MSCs) owing to their immunomodulatory functions and paracrine effects could serve as an effective alternative treatment option for rejuvenating the heart post MI. The major setback associated with the use of MSCs is reduced cell retention, engraftment and decreased effectiveness. With a few reports on understanding the role of inflammation and its dual effects on the structure and function of heart, this review focuses on these missing insights and further exemplifies the role of MSCs as an alternative therapy in treating the pathological consequences in myocardial infarction (MI).


Assuntos
Inflamação/patologia , Infarto do Miocárdio/terapia , Miocárdio/patologia , Regeneração , Transplante de Células-Tronco , Animais , Proliferação de Células , Ativação do Complemento , Fibrose , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Neutrófilos/citologia , Estresse Oxidativo , Células-Tronco Pluripotentes/citologia , Medicina Regenerativa/métodos
20.
Arch Cardiovasc Dis ; 113(4): 285-292, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32171698

RESUMO

Although the initial clinical trials of cardiac cell therapy have failed to demonstrate unequivocal clinical benefits, the accumulation of preclinical data gathered in parallel can now help us to understand the main causes of failures, while providing mechanistic insights that may be leveraged to improve the outcomes of subsequent clinical studies using cells or their secreted products. This review briefly describes the current status of clinical trials, discusses the potential mechanisms of action of the grafted cells, and the impact of this knowledge on the design of future studies, and finally draws some perspectives.


Assuntos
Insuficiência Cardíaca/cirurgia , Contração Miocárdica , Infarto do Miocárdio/cirurgia , Miocárdio/patologia , Regeneração , Transplante de Células-Tronco , Função Ventricular , Animais , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Sobrevivência de Enxerto , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos , Resultado do Tratamento
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