Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 67.654
Filtrar
1.
Braz. j. biol ; 84: e253061, 2024. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1364520

RESUMO

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.


A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados ​​como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.


Assuntos
Ratos , Células-Tronco , Fibrose , Fígado , Hepatopatias , Melatonina
2.
PeerJ ; 11: e14550, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36620748

RESUMO

Dental-derived stem cells have excellent proliferation ability and multi-directional differentiation potential, making them an important research target in tissue engineering. An increasing number of dental-derived stem cells have been discovered recently, including dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHEDs), stem cells from apical papilla (SCAPs), dental follicle precursor cells (DFPCs), and periodontal ligament stem cells (PDLSCs). These stem cells have significant application prospects in tissue regeneration because they are found in an abundance of sources, and they have good biocompatibility and are highly effective. The biological functions of dental-derived stem cells are regulated in many ways. Epigenetic regulation means changing the expression level and function of a gene without changing its sequence. Epigenetic regulation is involved in many biological processes, such as embryonic development, bone homeostasis, and the fate of stem cells. Existing studies have shown that dental-derived stem cells are also regulated by epigenetic modifications. Pulp and periodontal regeneration refers to the practice of replacing damaged pulp and periodontal tissue and restoring the tissue structure and function under normal physiological conditions. This treatment has better therapeutic effects than traditional treatments. This article reviews the recent research on the mechanism of epigenetic regulation of dental-derived stem cells, and the core issues surrounding the practical application and future use of pulp and periodontal regeneration.


Assuntos
Células-Tronco Mesenquimais , Humanos , Epigênese Genética , Células-Tronco/fisiologia , Ligamento Periodontal , Periodonto/fisiologia
3.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614220

RESUMO

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.


Assuntos
Induração Peniana , Masculino , Humanos , Induração Peniana/tratamento farmacológico , Pênis , Ereção Peniana , Injeções , Células-Tronco
4.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614288

RESUMO

The quest for eternal youth and immortality is as old as humankind. Ageing is an inevitable physiological process accompanied by many functional declines that are driving factors for age-related diseases. Stem cell exhaustion is one of the major hallmarks of ageing. The SOX transcription factors play well-known roles in self-renewal and differentiation of both embryonic and adult stem cells. As a consequence of ageing, the repertoire of adult stem cells present in various organs steadily declines, and their dysfunction/death could lead to reduced regenerative potential and development of age-related diseases. Thus, restoring the function of aged stem cells, inducing their regenerative potential, and slowing down the ageing process are critical for improving the health span and, consequently, the lifespan of humans. Reprograming factors, including SOX family members, emerge as crucial players in rejuvenation. This review focuses on the roles of SOX transcription factors in stem cell exhaustion and age-related diseases, including neurodegenerative diseases, visual deterioration, chronic obstructive pulmonary disease, osteoporosis, and age-related cancers. A better understanding of the molecular mechanisms of ageing and the roles of SOX transcription factors in this process could open new avenues for developing novel strategies that will delay ageing and prevent age-related diseases.


Assuntos
Células-Tronco Adultas , Fatores de Transcrição SOX , Adulto , Humanos , Adolescente , Idoso , Fatores de Transcrição SOX/genética , Envelhecimento/genética , Diferenciação Celular/fisiologia , Células-Tronco
5.
Proc Natl Acad Sci U S A ; 120(4): e2208176120, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36652477

RESUMO

Mutations in IDH1, IDH2, and TET2 are recurrently observed in myeloid neoplasms. IDH1 and IDH2 encode isocitrate dehydrogenase isoforms, which normally catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). Oncogenic IDH1/2 mutations confer neomorphic activity, leading to the production of D-2-hydroxyglutarate (D-2-HG), a potent inhibitor of α-KG-dependent enzymes which include the TET methylcytosine dioxygenases. Given their mutual exclusivity in myeloid neoplasms, IDH1, IDH2, and TET2 mutations may converge on a common oncogenic mechanism. Contrary to this expectation, we observed that they have distinct, and even opposite, effects on hematopoietic stem and progenitor cells in genetically engineered mice. Epigenetic and single-cell transcriptomic analyses revealed that Idh2R172K and Tet2 loss-of-function have divergent consequences on the expression and activity of key hematopoietic and leukemogenic regulators. Notably, chromatin accessibility and transcriptional deregulation in Idh2R172K cells were partially disconnected from DNA methylation alterations. These results highlight unanticipated divergent effects of IDH1/2 and TET2 mutations, providing support for the optimization of genotype-specific therapies.


Assuntos
Proteínas de Ligação a DNA , Dioxigenases , Isocitrato Desidrogenase , Células-Tronco , Animais , Camundongos , Dioxigenases/genética , Proteínas de Ligação a DNA/genética , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Ácidos Cetoglutáricos/metabolismo , Mutação , Neoplasias , Células-Tronco/metabolismo
6.
PeerJ ; 11: e14349, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36655039

RESUMO

Background: Ameloblastoma (AME) is characterized by a locally invasive growth pattern. In an attempt to justify the aggressiveness of neoplasms, the investigation of the role of stem cells has gained prominence. The SOX-2, NANOG and OCT4 proteins are important stem cell biomarkers. Methodology: To verify the expression of these proteins in tissue samples of AME, dentigerous cyst (DC) and dental follicle (DF), immunohistochemistry was performed and indirect immunofluorescence were performed on the human AME (AME-hTERT) cell line. Results: Revealed expression of SOX-2, NANOG and OCT4 in the tissue samples and AME-hTERT lineage. Greater immunostaining of the studied proteins was observed in AME compared to DC and DF (p < 0.001). Conclusions: The presence of biomarkers indicates a probable role of stem cells in the genesis and progression of AME.


Assuntos
Ameloblastoma , Células-Tronco Neoplásicas , Humanos , Ameloblastoma/genética , Ameloblastoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Imuno-Histoquímica , Proteína Homeobox Nanog/genética , Células-Tronco/metabolismo , Biomarcadores/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo
7.
Cell Metab ; 35(1): 12-35, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36599298

RESUMO

Both aging and cancer are characterized by a series of partially overlapping "hallmarks" that we subject here to a meta-analysis. Several hallmarks of aging (i.e., genomic instability, epigenetic alterations, chronic inflammation, and dysbiosis) are very similar to specific cancer hallmarks and hence constitute common "meta-hallmarks," while other features of aging (i.e., telomere attrition and stem cell exhaustion) act likely to suppress oncogenesis and hence can be viewed as preponderantly "antagonistic hallmarks." Disabled macroautophagy and cellular senescence are two hallmarks of aging that exert context-dependent oncosuppressive and pro-tumorigenic effects. Similarly, the equivalence or antagonism between aging-associated deregulated nutrient-sensing and cancer-relevant alterations of cellular metabolism is complex. The agonistic and antagonistic relationship between the processes that drive aging and cancer has bearings for the age-related increase and oldest age-related decrease of cancer morbidity and mortality, as well as for the therapeutic management of malignant disease in the elderly.


Assuntos
Epigênese Genética , Neoplasias , Humanos , Idoso , Envelhecimento/metabolismo , Senescência Celular , Células-Tronco/metabolismo , Neoplasias/metabolismo
8.
Subcell Biochem ; 102: 271-311, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36600137

RESUMO

Ageing is a complex process characterized by deteriorated performance at multiple levels, starting from cellular dysfunction to organ degeneration. Stem cell-based therapies aim to administrate stem cells that eventually migrate to the injured site to replenish the damaged tissue and recover tissue functionality. Stem cells can be easily obtained and cultured in vitro, and display several qualities such as self-renewal, differentiation, and immunomodulation that make them suitable candidates for stem cell-based therapies. Current animal studies and clinical trials are being performed to assess the safety and beneficial effects of stem cell engraftments for regenerative medicine in ageing and age-related diseases.Since alterations in cell-cell communication have been associated with the development of pathophysiological processes, new research is focusing on the modulation of the microenvironment. Recent research has highlighted the important role of some microenvironment components that modulate cell-cell communication, thus spreading signals from damaged ageing cells to neighbor healthy cells, thereby promoting systemic ageing. Extracellular vesicles (EVs) are small-rounded vesicles released by almost every cell type. EVs cargo includes several bioactive molecules, such as lipids, proteins, and genetic material. Once internalized by target cells, their specific cargo can induce epigenetic modifications and alter the fate of the recipient cells. Also, EV's content is dependent on the releasing cells, thus, EVs can be used as biomarkers for several diseases. Moreover, EVs have been proposed to be used as cell-free therapies that focus on their administration to slow or even reverse some hallmarks of physiological ageing. It is not surprising that EVs are also under study as next-generation therapies for age-related diseases.


Assuntos
Vesículas Extracelulares , Animais , Vesículas Extracelulares/metabolismo , Células-Tronco/metabolismo , Diferenciação Celular , Biomarcadores/metabolismo , Senescência Celular
9.
Subcell Biochem ; 102: 365-377, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36600140

RESUMO

In 1999, in a review by Beardsley, the potential of adult stem cells, in repair and regeneration was heralded (Beardsley Sci Am 281:30-31, 1999). Since then, the field of regenerative medicine has grown exponentially, with the capability of restoring or regenerating the function of damaged, diseased or aged human tissues being an underpinning motivation. If successful, stem cell therapies offer the potential to treat, for example degenerative diseases. In the subsequent 20 years, extensive progress has been made in the arena of adult stem cells (for a recent review see (Zakrzewski et al. Stem Cell Res Ther 10:68, 2019)). Prior to the growth of the adult stem cell research arena, much focus had been placed on the potential of embryonic stem cells (ESCs). The first research revealing the potential of these cells was published in 1981, when scientists reported the ability of cultured stem cells from murine embryos, to not only self-renew, but to also become all cells of the three germ layers of the developing embryo (Evans and Kaufman Nature 292:154-156, 1981), (Martin Proc Natl Acad Sci U S A 78:7634-7638, 1981). It took almost 20 years, following these discoveries, for this technology to translate to human ESCs, using donated human embryos. In 1998, Thomson et al. reported the creation of the first human embryonic cell line (Thomson et al. Science 282:1145-1147, 1998). However, research utilising human ESCs was hampered by ethical and religious constraints and indeed in 2001 George W. Bush restricted US research funding to human ESCs, which had already been banked. The contentious nature of this arena perhaps facilitated the use of and the research potential for adult stem cells. It is beyond the scope of this review to focus on ESCs, although their potential for enhancing our understanding of human development is huge (for a recent review see (Cyranoski Nature 555:428-430, 2018)). Rather, although ESCs and their epigenetic regulation will be introduced for background understanding, the focus will be on stem cells more generally, the role of epigenetics in stem cell fate, skeletal muscle, skeletal muscle stem cells, the impact of ageing on muscle wasting and the mechanisms underpinning loss, with a focus on epigenetic adaptation.


Assuntos
Epigênese Genética , Músculo Esquelético , Adulto , Camundongos , Humanos , Animais , Idoso , Músculo Esquelético/fisiologia , Diferenciação Celular , Células-Tronco , Envelhecimento
10.
Commun Biol ; 6(1): 43, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639551

RESUMO

Tissue stem cell niches are regulated by their mechanical environment, notably the extracellular matrix (ECM). Skeletal muscles consist of bundled myofibers for force transmission. Within this macroscopic architecture, quiescent Pax7-expressing (Pax7+) muscle stem cells (MuSCs) are compressed between ECM basally and myofiber apically. Muscle injury causes MuSCs to lose apical compression from the myofiber and re-enter the cell cycle for regeneration. While ECM elasticities have been shown to affect MuSC's renewal, the significance of apical compression remains unknown. To investigate the role of apical compression, we simulate the MuSCs' in vivo mechanical environment by applying physical compression to MuSCs' apical surface. We demonstrate that compression drives activated MuSCs back to a quiescent stem cell state, regardless of basal elasticities and chemistries. By mathematical modeling and cell tension manipulation, we conclude that low overall tension combined with high axial tension generated by compression leads to MuSCs' stemness and quiescence. Unexpectedly, we discovered that apical compression results in up-regulation of Notch downstream genes, accompanied by the increased levels of nuclear Notch1&3 in a Delta ligand (Dll) and ADAM10/17 independent manner. Our results fill a knowledge gap on the role of apical compression for MuSC fate and have implications to stem cells in other tissues.


Assuntos
Células Satélites de Músculo Esquelético , Nicho de Células-Tronco , Músculo Esquelético/metabolismo , Células-Tronco , Células Satélites de Músculo Esquelético/metabolismo
11.
Commun Biol ; 6(1): 75, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658332

RESUMO

Across complex, multi-time and -length scale biological systems, redundancy confers robustness and resilience, enabling adaptation and increasing survival under dynamic environmental conditions; this review addresses ubiquitous effects of cytoskeletal remodelling, triggered by biomechanical, biophysical and biochemical cues, on stem cell mechanoadaptation and emergent lineage commitment. The cytoskeleton provides an adaptive structural scaffold to the cell, regulating the emergence of stem cell structure-function relationships during tissue neogenesis, both in prenatal development as well as postnatal healing. Identification and mapping of the mechanical cues conducive to cytoskeletal remodelling and cell adaptation may help to establish environmental contexts that can be used prospectively as translational design specifications to target tissue neogenesis for regenerative medicine. In this review, we summarize findings on cytoskeletal remodelling in the context of tissue neogenesis during early development and postnatal healing, and its relevance in guiding lineage commitment for targeted tissue regeneration. We highlight how cytoskeleton-targeting chemical agents modulate stem cell differentiation and govern responses to mechanical cues in stem cells' emerging form and function. We further review methods for spatiotemporal visualization and measurement of cytoskeletal remodelling, as well as its effects on the mechanical properties of cells, as a function of adaptation. Research in these areas may facilitate translation of stem cells' own healing potential and improve the design of materials, therapies, and devices for regenerative medicine.


Assuntos
Citoesqueleto , Células-Tronco , Linhagem da Célula , Diferenciação Celular
12.
Ann Plast Surg ; 90(2): 171-179, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36688861

RESUMO

ABSTRACT: Platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) are known to secrete angiogenic factors that contribute to the treatment of intractable ulcers. The combination of PRP and ADSCs may enhance their angiogenic effects. However, it remains unclear whether treatment of ADSCs with PRP influences angiogenesis. We studied whether the conditioned medium from PRP-treated ADSCs under hypoxic conditions exerts angiogenic effects. Although PRP stimulated the proliferation of ADSCs obtained from rats, it decreased the mRNA levels of vascular endothelial growth factor, hepatocyte growth factor, and TGF-ß1, but not of basic fibroblast growth factor, under hypoxia. The conditioned medium of PRP-treated ADSCs inhibited endothelial nitric oxide synthase phosphorylation, decreased NO production, and suppressed tube formation in human umbilical vein endothelial cells. Transplantation of ADSCs alone increased both blood flow and capillary density of the ischemic limb; however, its combination with PRP did not further improve blood flow or capillary density. This suggests that both conditioned medium of ADSCs treated with PRP and combination of PRP with ADSCs transplantation may attenuate the phosphorylation of endothelial nitric oxide synthase and angiogenesis.


Assuntos
Plasma Rico em Plaquetas , Fator A de Crescimento do Endotélio Vascular , Humanos , Ratos , Animais , Meios de Cultivo Condicionados/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Óxido Nítrico Sintase Tipo III , Células Endoteliais da Veia Umbilical Humana/metabolismo , Neovascularização Fisiológica , Células-Tronco/metabolismo , Plasma Rico em Plaquetas/metabolismo , Tecido Adiposo/metabolismo , Células Cultivadas
13.
PLoS One ; 18(1): e0270380, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36689432

RESUMO

In order to get a better insight into the timing of WT1 mutant Wilms tumor development, we compared the gene expression profiles of nine established WT1 mutant Wilms tumor cell lines with published data from different kidney cell types during development. Publications describing genes expressed in nephrogenic precursor cells, ureteric bud cells, more mature nephrogenic epithelial cells and interstitial cell types were used. These studies uncovered that the WT1 mutant Wilms tumor cells lines express genes from the earliest nephrogenic progenitor cells, as well as from more differentiated nephron cells with the highest expression from the stromal/interstitial compartment. The expression of genes from all cell compartments points to an early developmental origin of the tumor in a common stem cell. Although variability of the expression of specific genes was evident between the cell lines the overall expression pattern was very similar. This is likely dependent on their different genetic backgrounds with distinct WT1 mutations and the absence/presence of mutant CTNNB1.


Assuntos
Neoplasias Renais , Tumor de Wilms , Humanos , Proteínas WT1/genética , Tumor de Wilms/patologia , Rim/patologia , Neoplasias Renais/patologia , Células-Tronco/metabolismo , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Expressão Gênica , Genes do Tumor de Wilms
14.
Eur Cell Mater ; 45: 1-13, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36625228

RESUMO

A critical component of the temporomandibular joint (TMJ) is the fibrocartilage articular disc (AD). Researchers have attempted to regenerate the AD to alleviate TMJ osteoarthritis but alternative cell sources for use in AD regenerative approaches are needed due to insufficient extracellular matrix (ECM) production by total articular disc cells (TACs). Tissue-specific progenitor cells have been identified in many tissues. The aim of the present study was to identify adult multipotent progenitor cells within the AD suitable for regenerative medicine applications. A novel AD progenitor cell population was identified in rhesus macaques. Clonally derived articular disc progenitor cells (ADPs) were isolated using fibronectin differential cell adhesion. ADPs represent between 1 and 3 % of the TAC population and are capable of in vitro expansion beyond 60 population doublings. ADPs were characterized using osteogenic, adipogenic, and fibrochondrogenesis differentiation assays. Clones exhibited phenotypic plasticity, differentiating into osteocytes, adipocytes, and fibrochondrocytes. ECM secretion profiles following fibrochondrogenic differentiation were assessed using immunohistochemistry (IHC), fluorescently activated cell sorting (FACS), total collagen, and glycosaminoglycan (GAG) assays and compared with TACs, articular cartilage progenitor cells (ACPs), tendon progenitor cells (TPCs) and bone-marrow-derived mesenchymal stem cells (BMMSCs). ADP pellet cultures produced a biochemical phenotype similar to native AD tissue, with production of versican (VCAN) and collagen types I, II, III, and VI (COL1, COL2, COL3, COL6). However, clonally derived ADP cell lines produced different amounts of ECM and exhibited different expansion potentials. These findings indicated flexibility in clone selection for potential regenerative strategies to recapitulate native anisotropy.


Assuntos
Cartilagem Articular , Células-Tronco , Animais , Macaca mulatta , Disco da Articulação Temporomandibular/metabolismo , Articulação Temporomandibular , Cartilagem Articular/metabolismo , Diferenciação Celular/genética , Células Clonais
15.
JCI Insight ; 8(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36625346

RESUMO

The liver is a highly regenerative organ, yet the presence of a dedicated stem cell population remains controversial. Here, we interrogate a severe hepatocyte injury model in adult zebrafish to define that regeneration involves a stem cell population. After near-total hepatocyte ablation, single-cell transcriptomic and high-resolution imaging analyses throughout the entire regenerative timeline reveal that biliary epithelial cells undergo transcriptional and morphological changes to become hepatocytes. As a population, biliary epithelial cells give rise to both hepatocytes and biliary epithelial cells. Biliary epithelial cells proliferate and dedifferentiate to express hepatoblast transcription factors prior to hepatocyte differentiation. This process is characterized by increased MAPK, PI3K, and mTOR signaling, and chemical inhibition of these pathways impairs biliary epithelial cell proliferation and fate conversion. We conclude that, upon severe hepatocyte ablation in the adult liver, biliary epithelial cells act as facultative liver stem cells in an EGFR-PI3K-mTOR-dependent manner.


Assuntos
Regeneração Hepática , Peixe-Zebra , Animais , Regeneração Hepática/fisiologia , Fígado , Células Epiteliais , Células-Tronco , Serina-Treonina Quinases TOR , Fosfatidilinositol 3-Quinases
16.
Sci Rep ; 13(1): 74, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593314

RESUMO

Tissue injury affects nerve fibers and triggers an immune response, leading to inflammation. The complement system gets activated during inflammatory conditions and has been reported to be involved in the regeneration process. We have demonstrated that the C5a receptor (C5aR) has crucial roles in regeneration and healing processes including nerve sprouting and hard tissue formation. Another C5a-like 2 receptor (C5AR2; C5L2) has been cloned which is still considered controversial due to limited studies. We previously established that C5L2 regulates brain-derived neurotrophic factor (BDNF) secretion in pulp fibroblasts. However, there is no study available on human dental pulp stem cells (DPSCs), especially in the inflammatory context. Stem cell therapy is an emerging technique to treat and prevent several diseases. DPSCs are a great option to be considered due to their great ability to differentiate into a variety of cells and secrete nerve regeneration factors. Here, we demonstrated that C5L2 modulates BDNF secretion in DPSCs. Our results stated that C5L2 silencing through siRNA could increase BDNF production, which could accelerate the nerve regeneration process. Moreover, stimulation with lipopolysaccharide (LPS) enhanced BDNF production in C5L2 silenced DPSCs. Finally, we quantified BDNF secretion in supernatant and cell lysates using ELISA. Our results showed enhanced BDNF production in C5L2 silenced DPSCs and hampered by the p38MAPKα inhibitor. Taken together, our data reveal that C5L2 modulates BDNF production in DPSCs via the p38MAPKα pathway.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Polpa Dentária , Receptor da Anafilatoxina C5a , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Polpa Dentária/metabolismo , Fibras Nervosas/metabolismo , Regeneração Nervosa/fisiologia , Receptor da Anafilatoxina C5a/genética , Receptor da Anafilatoxina C5a/metabolismo , Células-Tronco/metabolismo , Proteína Quinase 14 Ativada por Mitógeno/metabolismo
17.
Arthroscopy ; 39(2): 371-372, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36604003

RESUMO

The goal of meniscal tissue engineering is tissue remodeling and functional recovery. Autologous, tissue-engineered adipose-derived stem cell (ADSC) sheets promote meniscal regeneration in rabbit meniscal defects in vivo. Moreover, compared with a control group, in the ADSC sheet model, both histologic scores and gene expression are more similar to normal meniscal tissue. ADSC sheets promote meniscal regeneration regardless of whether the defect involves the whole width or inner half of a meniscal defect. Mechanical properties are also important, and experimental data show encouraging mechanical properties of meniscus tissue reconstructed from ADSC sheets. Cell sheet technology is a promising therapeutic strategy for meniscal regenerative medicine and tissue engineering. Theoretically, cell sheet transplantation could result in superior outcomes to traditional cell-free scaffolds, and further research is needed before clinical application.


Assuntos
Menisco , Animais , Coelhos , Engenharia Tecidual , Regeneração , Células-Tronco
18.
J Cell Sci ; 136(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36594556

RESUMO

Cancer cells have heterogeneous fitness, and this heterogeneity stems from genetic and epigenetic sources. Here, we sought to assess the contribution of asymmetric mitosis (AM) and time on the variability of fitness in sister cells. Around one quarter of sisters had differences in fitness, assessed as the intermitotic time (IMT), from 330 to 510 min. Phenotypes related to fitness, such as ERK activity (herein referring to ERK1 and ERK2, also known as MAPK3 and MAPK1, respectively), DNA damage and nuclear morphological phenotypes were also asymmetric at mitosis or turned asymmetric over the course of the cell cycle. The ERK activity of mother cell was found to influence the ERK activity and the IMT of the daughter cells, and cells with ERK asymmetry at mitosis produced more offspring with AMs, suggesting heritability of the AM phenotype for ERK activity. Our findings demonstrate how variabilities in sister cells can be generated, contributing to the phenotype heterogeneities in tumor cells.


Assuntos
Divisão do Núcleo Celular , Mitose , Mitose/genética , Ciclo Celular , Fosforilação , Células-Tronco
19.
Indian J Ophthalmol ; 71(1): 75-79, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36588212

RESUMO

Purpose: To investigate the effects of riboflavin and/or ultraviolet-A (UV-A) irradiation on the cell viability of ex-vivo-cultured rat limbal stem cells (LSCs). Methods: LSCs of male Wistar rats (N = 12 eyes) were cultured, and immunofluorescence staining was performed to evaluate them. After characterization, these cells were assigned to four groups of control (C), a group that was exposed to UV-A radiation (UV), a group that was treated with riboflavin (R), and a group that cotreated with both UV-A and riboflavin (UV+R). To determine the cell viability of LSCs, these cells were subjected to MTT assay on days 1, 3, and 7 after exposure to UV-A and/or riboflavin. The duration of exposure to UV-A and riboflavin was similar to levels used during the conventional corneal collagen cross-linking procedure. Results: Compared with the viable cells in the control group, there was a significant decrease (P < 0.0001) in the number of LSCs in the UV group during all study days. In the R group, the level of viable LSCs was as same as the level of viable LSCs in the C group. Combined treatment with UV-A plus riboflavin significantly decreased the survival of LSCs on days 1 and 3 (P < 0.0001, P < 0.001, respectively) compared with the control group. Interestingly, in the UV+R group, the photosensitizing effect of riboflavin significantly decreased the cytotoxic effect of UV irradiation 7 days after exposure. Conclusion: These results suggest that the administered UV energy in the presence or absence of riboflavin can damage LSCs. Likewise, riboflavin could decrease the toxic effect of UVA on LSCs.


Assuntos
Fármacos Fotossensibilizantes , Riboflavina , Masculino , Animais , Ratos , Ratos Wistar , Riboflavina/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Raios Ultravioleta , Células-Tronco , Reagentes de Ligações Cruzadas/farmacologia , Córnea , Substância Própria
20.
Am J Sports Med ; 51(1): 66-80, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36592017

RESUMO

BACKGROUND: Stem cell sheets provide a scaffold-free option for the promotion of graft healing after anterior cruciate ligament reconstruction (ACLR). However, cell viability, stability, and potential uncontrolled actions create challenges for clinical translation. The decellularization of cell sheets may overcome these problems as studies have shown that the natural extracellular matrix of stem cells is bioactive and can promote tissue repair. HYPOTHESIS: The decellularized tendon-derived stem cell (dTDSC) sheet can promote graft healing after ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: An optimized decellularization protocol was developed to decellularize the TDSC sheets. A total of 64 Sprague-Dawley rats underwent ACLR with or without the dTDSC sheet wrapping the tendon graft (n = 32/group). At 2 and 6 weeks after surgery, graft healing was assessed by micro-computed tomography, histology, and biomechanical testing. The accumulation of iNOS+ and CD206+ cells and the expression of metalloproteinase 1 (MMP-1), MMP-13, and tissue inhibitor of metalloprotease 1 (TIMP-1) were assessed by immunohistochemistry. RESULTS: The decellularization was successful, with the removal of 98.4% nucleic acid while preserving the collagenous proteins and bioactive factors. The expression of bone morphogenetic protein 2 (BMP-2) and VEGF in the dTDSC sheet was comparable with the TDSC sheet (P > .05). Micro-computed tomography showed significantly more tunnel bone formation in the dTDSC sheet group. The dTDSC sheet group demonstrated better graft osteointegration and higher integrity of graft midsubstance with significantly higher ultimate failure load (16.58 ± 7.24 vs 8.93 ± 2.45 N; P = .002) and stiffness (11.97 ± 5.21 vs 6.73 ± 2.20 N/mm; P = .027). Significantly fewer iNOS+ cells but more CD206+ cells, as well as lower MMP-1 and MMP-13 but higher TIMP-1 expression, were detected at the tendon-bone interface and graft midsubstance in the dTDSC sheet group. CONCLUSION: An optimized decellularization protocol for producing bioactive dTDSC sheets was developed. Wrapping tendon graft with a dTDSC sheet promoted graft healing after ACLR, likely via enhancing bone formation and angiogenesis by BMP-2 and VEGF, modulating macrophage polarization and MMP/TIMP expression, and physically protecting the tendon graft. CLINICAL RELEVANCE: dTDSC sheets alleviate the quality control and safety concerns of cell transplantation and can be used as a cell-free alternative for the promotion of graft healing in ACLR.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Ratos , Animais , Ligamento Cruzado Anterior/cirurgia , Metaloproteinase 13 da Matriz , Ratos Sprague-Dawley , Microtomografia por Raio-X , Metaloproteinase 1 da Matriz , Inibidor Tecidual de Metaloproteinase-1 , Fator A de Crescimento do Endotélio Vascular , Tendões/cirurgia , Células-Tronco , Reconstrução do Ligamento Cruzado Anterior/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...