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1.
Sci Rep ; 12(1): 1812, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35110659

RESUMO

The induction and direction of stem cell differentiation into needed cell phenotypes is the central pillar of tissue engineering for repairing damaged tissues or organs. Conventionally, a special recipe of chemical factors is formulated to achieve this purpose for each specific target cell type. In this work, it is demonstrated that the combination of extrinsic photobiomodulation and collagen-covered microislands could be used to induce differentiation of Wharton's jelly mesenchymal stem cells (WJ-MSCs) with the differentiation direction dictated by the specific island topography without use of chemical factors. Both neurogenic differentiation and adipogenic differentiation could be attained with a rate surpassing that using chemical factors. Application of this method to other cell types is possible by utilizing microislands with a pattern tailored particularly for each specific cell type, rendering it a versatile modality for initiating and guiding stem cell differentiation.


Assuntos
Adesão Celular , Diferenciação Celular/efeitos da radiação , Colágeno/fisiologia , Luz , Células-Tronco Mesenquimais/efeitos da radiação , Engenharia Tecidual , Adipogenia/efeitos da radiação , Técnicas de Cultura de Células , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/fisiologia , Neurogênese/efeitos da radiação , Geleia de Wharton/citologia
2.
Mol Cell Endocrinol ; 521: 111110, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33285245

RESUMO

The circadian clock exerts temporal coordination of metabolic pathways. Clock disruption is intimately linked with the development of obesity and insulin resistance, and our previous studies found that the essential clock transcription activator, Brain and Muscle Arnt-like 1 (Bmal1), is a key regulator of adipogenesis. However, the metabolic consequences of chronic shiftwork on adipose tissues have not been clearly defined. Here, using an environmental lighting-induced clock disruption that mimics rotating shiftwork schedule, we show that chronic clock dysregulation for 6 months in mice resulted in striking adipocyte hypertrophy with adipose tissue inflammation and fibrosis. Both visceral and subcutaneous depots display enlarged adipocyte with prominent crown-like structures indicative of macrophage infiltration together with evidence of extracellular matrix remodeling. Global transcriptomic analyses of these fat depots revealed that shiftwork resulted in up-regulations of inflammatory, adipogenic and angiogenic pathways with disruption of normal time-of-the-day-dependent regulation. These changes in adipose tissues are associated with impaired insulin signaling in mice subjected to shiftwork, together with suppression of the mTOR signaling pathway. Taken together, our study identified the significant adipose depot dysfunctions induced by chronic shiftwork regimen that may underlie the link between circadian misalignment and insulin resistance.


Assuntos
Adipócitos/citologia , Adipogenia/genética , Tecido Adiposo/metabolismo , Relógios Circadianos/efeitos da radiação , Fibrose/metabolismo , Regulação da Expressão Gênica/genética , Fotoperíodo , Adipócitos/metabolismo , Adipócitos/patologia , Adipócitos/efeitos da radiação , Adipogenia/efeitos da radiação , Tecido Adiposo/citologia , Tecido Adiposo/efeitos da radiação , Animais , Relógios Circadianos/genética , Regulação para Baixo , Fibrose/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos da radiação , Ontologia Genética , Inflamação/genética , Inflamação/metabolismo , Resistência à Insulina/genética , Resistência à Insulina/efeitos da radiação , Macrófagos/metabolismo , Macrófagos/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Serina-Treonina Quinases TOR/metabolismo , Transcriptoma/genética , Transcriptoma/efeitos da radiação , Regulação para Cima
3.
Biochem Biophys Res Commun ; 520(2): 420-427, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31607480

RESUMO

Irradiation induces severe damage in the hematopoietic system, which leads to bone marrow hyperplasia, pancytopenia, and aggravated tissue formation in bone marrow. Studies have shown that Toll-like receptor 4 (TLR4) has a protective effect against irradiation, but the underlying mechanism remains unclear. In this study, we used a TLR4 knockout (TLR4-/-) mouse irradiation model and found that the white blood cell and platelet counts in the peripheral blood of TLR4-/- mice recovered slowly after irradiation, with bone marrow hyperplasia and increased mortality. Additionally, we found that the proportion of CD11b+Gr1+ granulocytes in the peripheral blood and bone marrow of TLR4-/- mice was lower than that of wild-type mice after irradiation. Further, we found that the expression of NADPH Oxidases (NOXs) in the bone marrow was down-regulated after irradiation of TLR4-/- mice, and administration of the NOXs inhibitor VAS2870 reduced the proportion of CD11b+Gr1+ cells in the bone marrow and peripheral blood of wild-type mice after irradiation. Irradiation induced severe marrow adipocytes accumulation in TLR4-/- mice, TLR4 ligand lipopolysaccharide promoted proliferation and inhibited adipogenic differentiation of mesenchymal stromal cells. In summary, our data suggest that TLR4 promotes myeloid hyperplasia by up-regulating the expression of NOXs after irradiation, prohibits marrow adipogensis and increases the tolerance of mice to irradiation.


Assuntos
Adipogenia/efeitos da radiação , Lesões Experimentais por Radiação/patologia , Receptor 4 Toll-Like/metabolismo , Irradiação Corporal Total/efeitos adversos , Animais , Benzoxazóis/farmacologia , Medula Óssea/metabolismo , Medula Óssea/efeitos da radiação , Diferenciação Celular , Células Cultivadas , Granulócitos/patologia , Hematopoese/efeitos da radiação , Lipopolissacarídeos/farmacologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos da radiação , Camundongos Endogâmicos C57BL , Camundongos Mutantes , NADPH Oxidases/metabolismo , Lesões Experimentais por Radiação/metabolismo , Receptor 4 Toll-Like/genética , Triazóis/farmacologia
4.
Transfusion ; 59(3): 1069-1079, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30793328

RESUMO

BACKGROUND: Human platelet lysate (hPL) represents a powerful medium supplement for human mesenchymal stromal cell (hMSC) expansion. The recently published general chapters of the Pharmacopeia require the addition of a step of viral inactivation during the production process of such raw biological material used for cell-based medicinal products. STUDY DESIGN AND METHODS: The ability of gamma irradiation to inactivate viruses from a panel representative of the virus diversity was evaluated. The impact of gamma irradiation on hPL composition and efficiency as a supplement for hMSC culture was evaluated. RESULTS: An efficient inactivation of all the viruses tested was demonstrated, with the minimum reduction factors obtained being superior to 4.5 log10 for human immunodeficiency virus (HIV) and hepatitis A virus (HAV) and superior to 5 log10 for bovine viral diarrhea virus (BVDV), pseudorabies virus (PRV) and porcine parvovirus (PPV). The gamma irradiation did not affect the content in interesting biochemical factors for cell culture or in growth factors (GF), except to basic fibroblast GF (bFGF) whereas it highly impacted the contents in the factors involved in the coagulation cascade. Finally, gamma irradiated hPL remained as efficient as non-irradiated hPL for the proliferation, clonogenic potential, differentiation potential, and immunosuppressive properties of hMSCs. CONCLUSION: The feasibility of using gamma irradiation to efficiently inactivate viruses in hPL while maintaining its optimal efficacy as a supplement for hMSC expansion was demonstrated. Such an inactivated hPL represents a very attractive raw material for the efficient production of safe cellular therapy products.


Assuntos
Raios gama , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos da radiação , Inativação de Vírus/efeitos da radiação , Adipogenia/efeitos da radiação , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos da radiação , Técnicas de Cultura de Células , Proliferação de Células/fisiologia , Humanos , Osteogênese/efeitos da radiação
5.
Int J Mol Sci ; 19(9)2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30208657

RESUMO

Radiotherapy is a widely used treatment option for cancer patients as well as for patients with musculoskeletal disorders. Adipocytes, the dominant cell type of adipose tissue, are known to constitute an active part of the tumor microenvironment. Moreover, adipocytes support inflammatory processes and cartilage degradation in chronic inflammatory diseases, i.e., rheumatoid and osteoarthritis. Since the production of inflammatory factors is linked to their differentiation stages, we set out to explore the radiation response of pre-adipocytes that may influence their inflammatory potential and differentiation capacity. This is the first study investigating the effects of X-ray irradiation on the proliferation and differentiation capacity of human primary pre-adipocytes, in comparison to Simpson⁻Golabi⁻Behmel Syndrome (SGBS) pre-adipocytes, an often-used in vitro model of human primary pre-adipocytes. Our results demonstrate a dose-dependent reduction of the proliferation capacity for both cell strains, whereas the potential for differentiation was mostly unaffected by irradiation. The expression of markers of adipogenic development, such as transcription factors (PPARγ, C/EBPα and C/EBPß), as well as the release of adipokines (visfatin, adiponectin and leptin) were not significantly changed upon irradiation. However, after irradiation with high X-ray doses, an increased lipid accumulation was observed, which suggests a radiation-induced response of adipocytes related to inflammation. Our results indicate that pre-adipocytes are radio-resistant, and it remains to be elucidated whether this holds true for the overall inflammatory response of adipocytes upon irradiation.


Assuntos
Adipócitos/efeitos da radiação , Adipogenia/efeitos da radiação , Proliferação de Células/efeitos da radiação , Adipócitos/citologia , Adipócitos/metabolismo , Adipocinas/metabolismo , Arritmias Cardíacas/metabolismo , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Gigantismo/metabolismo , Cardiopatias Congênitas/metabolismo , Humanos , Deficiência Intelectual/metabolismo , Raios X
6.
Biol Blood Marrow Transplant ; 24(3): 443-451, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29155314

RESUMO

Bone marrow mesenchymal stromal cells (MSCs) are precursors of adipocytes and osteoblasts and key regulators of hematopoiesis. Irradiation is widely used in conditioning regimens. Although MSCs are radio-resistant, the effects of low-dose irradiation on their behavior have not been extensively explored. Our aim was to evaluate the effect of 2.5 Gy on MSCs. Cells from 25 healthy donors were either irradiated or not (the latter were used as controls). Cells were characterized following International Society for Cellular Therapy criteria, including in vitro differentiation assays. Apoptosis was evaluated by annexin V/7-amino-actinomycin staining. Gene expression profiling and reverse transcriptase (RT)-PCR of relevant genes was also performed. Finally, long-term bone marrow cultures were performed to test the hematopoietic-supporting ability. Our results showed that immunophenotypic characterization and viability of irradiated cells was comparable with that of control cells. Gene expression profiling showed 50 genes differentially expressed. By RT-PCR, SDF-1 and ANGPT were overexpressed, whereas COL1A1 was downregulated in irradiated cells (P = .015, P = .007, and P = .031, respectively). Interestingly, differentiation of irradiated cells was skewed toward osteogenesis, whereas adipogenesis was impaired. Higher expression of genes involved in osteogenesis as SPP1 (P = .039) and lower of genes involved in adipogenesis, CEBPA and PPARG (P = .003 and P = .019), together with an increase in the mineralization capacity (Alizarin Red) was observed in irradiated cells. After differentiation, adipocyte counts were decreased in irradiated cells at days 7, 14, and 21 (P = .018 P = .046, and P = .018, respectively). Also, colony-forming unit granulocyte macrophage number in long-term bone marrow cultures was significantly higher in irradiated cells after 4 and 5 weeks (P = .046 and P = .007). In summary, the irradiation of MSCs with 2.5 Gy improves their hematopoietic-supporting ability by increasing osteogenic differentiation and decreasing adipogenesis.


Assuntos
Adipogenia/efeitos da radiação , Diferenciação Celular/efeitos da radiação , Raios gama , Hematopoese/efeitos da radiação , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos da radiação , Adulto , Idoso , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade
7.
J Nutr Sci Vitaminol (Tokyo) ; 63(3): 161-166, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28757529

RESUMO

To explore the protective effects of 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) on the bone marrow microenvironment in mice after irradiation and the underlying molecular mechanisms, a total of 150 7-wk-old male BALB/c mice were randomly divided into a normal group, an irradiation (IR) group and an irradiation+1,25-(OH)2D3 (IR+VD3) group. The mice in the IR+VD3 group were treated with 6.0 Gy 60Coγ rays, and 1,25-(OH)2D3 (dissolved in DMSO, 2.5 µg/kg) was administered once per day from 2 d before to 8 d after irradiation. Mice in the IR group were treated with the same dose of γ rays and an equal volume of DMSO. Subsequently, the body weights and the numbers of peripheral white blood cells (WBCs) were measured. Histological analysis of femur bone marrow was conducted to determine the proportion of adipose area as well. Finally, the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) in bone marrow was detected by immunohistochemistry. After irradiation, the percentage of adipose area in the bone marrow was significantly increased, and the WBC number and body weight were markedly reduced. Compared with irradiation alone, the co-administration of 1,25-(OH)2D3 with irradiation markedly attenuated radiation-induced adipogenesis in bone marrow, resulted in fewer bone marrow stromal cells expressing PPARγ and enhanced the recovery of body weight and WBCs. These results indicate that 1,25-(OH)2D3 could accelerate the recovery of body weight and WBCs in irradiated mice and protect the bone marrow by inhibiting radiation-induced adipogenesis via the down-regulation of PPARγ expression.


Assuntos
Adipogenia/efeitos dos fármacos , Adipogenia/efeitos da radiação , Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos da radiação , Raios gama/efeitos adversos , Vitamina D/análogos & derivados , Adipócitos/efeitos dos fármacos , Adipócitos/efeitos da radiação , Animais , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Regulação da Expressão Gênica , Contagem de Leucócitos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , PPAR gama/genética , PPAR gama/metabolismo , Vitamina D/farmacologia
8.
Sci Rep ; 7(1): 909, 2017 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-28424532

RESUMO

Ultraviolet A (UVA) irradiation exerts negative effects on stemness and differentiation potential of stem cells. This study aimed to explore the effect of sinapic acid on UVA-irradiation-induced damages to stemness and differentiation potential of human-adipose-tissue-derived mesenchymal stem cells (hAMSCs) and its UVA-antagonist mechanisms. Sinapic acid attenuated UVA-induced reduction in the proliferative potential and stemness by upregulating OCT4, SOX2, and NANOG. In addition, sinapic acid significantly recovered UVA-induced reduction in expression level of hypoxia-inducible factor (HIF)-1α. The antagonist effect of sinapic acid against stemness damage was mediated by reduceing PGE2 production through inhibition of p38 MAPK and NF-κB. Moreover, sinapic acid attenuated UVA-induced reduction in differentiation potential by downregulating the expression of macrophage migration inhibitory factor (MIF) and Kruppel-like factor (KLF) 2 gene while activating AMP-activated protein kinase (AMPK). UVA-induced inhibition of adipogenic differentiation was mediated by reducing MIF production through suppression of NF-κB. Taken together, these findings suggest that sinapic acid may ameliorate UVA-irradiation-induced reduced stemness and differentiation potential of hAMSCs. Therefore, sinapic acid might have potential as an antagonist agent to attenuate damages caused by UVA.


Assuntos
Adipogenia/efeitos dos fármacos , Adipogenia/efeitos da radiação , Tecido Adiposo/citologia , Ácidos Cumáricos/farmacologia , Dano ao DNA/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/efeitos da radiação , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos da radiação , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Stem Cell Res Ther ; 8(1): 71, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28320453

RESUMO

BACKGROUND: While it is known that irradiation can induce local and systemic bone loss over time, how focal irradiation induces systemic bone complications remains unclear. Immune cells are thought to be crucial to bone homeostasis, and abnormal immune cells lead to serious disruption of bone homeostasis, such as in acute lymphoblastic leukaemia. This disruption primarily occurs due to inhibition of the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). METHODS: In this study, we detected local and systemic bone loss in trabecular bone by micro-computed tomography (micro-CT) and measurement of peroxisome proliferator-activated receptor gamma (PPARγ) and runt-related transcription factor 2 (RUNX2) expression in BMSCs using real-time polymerase chain reaction and western blotting. Additionally, changes in lymphocytes (B cells and CD4+ and CD8+ T cells) in the peripheral blood and bone marrow were analysed by flow cytometry. BMSC-derived osteoblasts and adipocytes, cultured in osteogenic or adipogenic media or co-cultured with lymphocytes, were detected by BCIP/NBT, Alizarin Red S and Oil Red O staining. RESULTS: Focal irradiation induced local and systemic bone loss in trabecular bone. Increased PPARγ expression and decreased RUNX2 expression were observed, accompanied by upregulated adipogenesis and downregulated osteogenesis of BMSCs. B cells and CD8+ T lymphocytes were increased in the blood and bone marrow after irradiation, while CD4+ T lymphocytes were decreased in the blood. Inhibition of RUNX2 expression and reduction of alkaline phosphatase activity and mineralization deposits were observed in lymphocyte-co-cultured BMSCs, accompanied by an increase in PPARγ expression and in the number of lipid droplets. CONCLUSIONS: Focal irradiation induced local and systemic bone loss in trabecular bone. Increased B cells and CD8+ T lymphocytes led to systemic bone loss by decreasing BMSC osteogenesis.


Assuntos
Adipogenia/efeitos da radiação , Células da Medula Óssea/citologia , Raios gama , Linfócitos/citologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos da radiação , Osteogênese/efeitos da radiação , Adipócitos/metabolismo , Adipócitos/efeitos da radiação , Animais , Células da Medula Óssea/efeitos da radiação , Relação Dose-Resposta à Radiação , Citometria de Fluxo , Contagem de Linfócitos , Linfócitos/efeitos da radiação , Masculino , Osteoblastos/metabolismo , Osteoblastos/efeitos da radiação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley
10.
Stem Cell Res ; 17(3): 646-653, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27865162

RESUMO

Pre-transplant myeloablation is associated with marrow adipogenesis, resulting in delayed engraftment of hematopoietic stem cells (HSCs). This is strongly undesirable, especially when the donor HSCs are fewer in numbers or have compromised functionality. The molecular mechanisms behind irradiation-induced marrow adipogenesis have not been extensively investigated. Here we show that bone marrow (BM) cells, especially T-cells and stromal cells, express and secrete copious amounts of BMP4 in response to irradiation, which causes the bone marrow stromal cells to commit to adipocyte lineage, thereby contributing to an increase in bone marrow adipogenesis. We further demonstrate that Simvastatin inhibits the BMP4-mediated adipogenic commitment of marrow stromal cells by inhibiting Ppar-γ expression. Importantly, Simvastatin does not prevent BMP4 secretion by the BM cells, and thus does not interfere with its salutary role in post-transplant hematopoietic regeneration. Our data identify previously unknown mechanisms operative in marrow adipogenesis post-myeloablation. They also reveal the molecular mechanisms behind the advantage of using Simvastatin as a niche-targeting agent to improve HSC engraftment.


Assuntos
Adipogenia/efeitos da radiação , Células da Medula Óssea/efeitos da radiação , Proteína Morfogenética Óssea 4/metabolismo , Adipócitos/citologia , Adipócitos/efeitos da radiação , Adipogenia/fisiologia , Animais , Células da Medula Óssea/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/biossíntese , Taxa Secretória/efeitos dos fármacos , Taxa Secretória/efeitos da radiação , Sinvastatina/farmacologia , Células Estromais/metabolismo , Células Estromais/efeitos da radiação , Linfócitos T/metabolismo , Linfócitos T/efeitos da radiação , Irradiação Corporal Total
11.
Stem Cell Res Ther ; 7(1): 117, 2016 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-27530249

RESUMO

BACKGROUND: Adipose-derived stem cells (ASCs) are important to homeostasis and the regeneration of subcutaneous fat. Hence, we examined the proliferation and differentiation capacity of irradiated ASCs over time. METHODS: Two female pigs received a single 18 Gy dose of ionizing radiation to an 18 × 8 cm area on the dorsal body skin via a 6 MeV electron beam. After irradiation, the ASCs were cultured from adipose tissue harvested from a non-irradiated area and an irradiated area at 2, 4, and 6 weeks. The proliferation capacity of ASCs was evaluated by a colony-forming units-fibroblasts (CFUs-Fs) assay, a cholecystokinin (CCK) test with 10 % fetal bovine serum (FBS), and a 1 % FBS culture test. The senescence of ASCs was evaluated through morphological examination, immunophenotyping, and ß-galactosidase activity, and the multipotent differentiation potential of ASCs was evaluated in adipogenic, osteogenic, and chondrogenic differentiation media. RESULTS: Irradiated ASCs demonstrated significantly decreased proliferative capacity 6 weeks after irradiation. As well, the cells underwent senescence, which was confirmed by blunted morphology, weak mesenchymal cell surface marker expression, and elevated ß-galactosidase activity. Irradiated ASCs also exhibited significant losses in the capacity for adipocyte and chondrocyte differentiation. In contrast, osteogenic differentiation was preserved in irradiated ASCs. CONCLUSIONS: We observed decreased proliferation and senescence of irradiated ASCs compared to non-irradiated ASCs 6 weeks after irradiation. Furthermore, irradiated ASCs demonstrated impaired adipocyte and chondrocyte differentiation but retained their osteogenic differentiation capacity. Our results could shed light on additional pathogenic effects of late irradiation, including subcutaneous fibrosis and calcinosis.


Assuntos
Adipócitos/efeitos da radiação , Tecido Adiposo/efeitos da radiação , Diferenciação Celular/fisiologia , Diferenciação Celular/efeitos da radiação , Proliferação de Células/fisiologia , Proliferação de Células/efeitos da radiação , Células-Tronco/efeitos da radiação , Adipócitos/metabolismo , Adipócitos/fisiologia , Adipogenia/fisiologia , Adipogenia/efeitos da radiação , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiologia , Animais , Células Cultivadas , Condrócitos/metabolismo , Condrócitos/fisiologia , Condrócitos/efeitos da radiação , Condrogênese/fisiologia , Condrogênese/efeitos da radiação , Feminino , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Fibroblastos/efeitos da radiação , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Células-Tronco Mesenquimais/efeitos da radiação , Osteogênese/fisiologia , Osteogênese/efeitos da radiação , Radiação Ionizante , Células-Tronco/metabolismo , Células-Tronco/fisiologia , Gordura Subcutânea/metabolismo , Suínos , beta-Galactosidase/metabolismo
12.
Mol Med Rep ; 13(4): 3377-83, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26936439

RESUMO

Combined radiation and wound injury (CRWI) occurs following nuclear explosions and accidents, radiological or nuclear terrorism, and radiation therapy combined with surgery. CRWI is complicated and more difficult to heal than single injuries. Stem cell­based therapy is a promising treatment strategy for CRWI, however, sourcing stem cells remains a challenge. In the present study, the granulation tissue-derived cells (GTCs) from the skin wounds (SWs) of CRWI mice (C­GTCs) demonstrated a higher radioresistance to the damage caused by combined injury, and were easier to isolate and harvest when compared with bone marrow­derived mesenchymal stromal cells (BMSCs). Furthermore, the C-GTCs exhibited similar stem cell-associated properties, such as self-renewal and multilineage differentiation capacity, when compared with neonatal dermal stromal cells (DSCs) and GTCs from unirradiated SWs. Granulation tissue, which is easy to access, may present as an optimal autologous source of stem/progenitor cells for therapeutic applications in CRWI.


Assuntos
Tecido de Granulação/citologia , Pele/lesões , Irradiação Corporal Total , Adipogenia/efeitos da radiação , Animais , Células da Medula Óssea/citologia , Adesão Celular/efeitos da radiação , Diferenciação Celular/efeitos da radiação , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Células Cultivadas , Senescência Celular/efeitos da radiação , Feminino , Raios gama , Tecido de Granulação/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Osteogênese/efeitos da radiação , Tolerância a Radiação , Pele/citologia , Pele/efeitos da radiação
13.
Oncotarget ; 7(6): 6410-23, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26843618

RESUMO

Extracorporeal shock wave therapy (ESWT) is a non-invasive and innovative technology for the management of specific tendinopathies. In order to elucidate the ESWT-mediated clinical benefits, human Tendon-derived Stem/Progenitor cells (hTSPCs) explanted from 5 healthy semitendinosus (ST) and 5 ruptured Achilles (AT) tendons were established. While hTSPCs from the two groups showed similar proliferation rates and stem cell surface marker profiles, we found that the clonogenic potential was maintained only in cells derived from healthy donors. Interestingly, ESWT significantly accelerated hTSPCs differentiation, suggesting that the clinical benefits of ESWT may be ascribed to increased efficiency of tendon repair after injury.


Assuntos
Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Ondas de Choque de Alta Energia , Células-Tronco/citologia , Traumatismos dos Tendões/patologia , Tendões/citologia , Adipogenia/efeitos da radiação , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Células Cultivadas , Imunofluorescência , Humanos , Técnicas In Vitro , Osteogênese/efeitos da radiação , Células-Tronco/fisiologia , Células-Tronco/efeitos da radiação , Traumatismos dos Tendões/radioterapia , Tendões/fisiologia , Tendões/efeitos da radiação
14.
Int J Obes (Lond) ; 40(5): 824-32, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26607039

RESUMO

BACKGROUND: Recent studies have led to an expansion of potential factors capable of stimulating obesity. Increasing evidence indicates that environmental factors, including disturbance of circadian rhythms, also contribute to its etiology. OBJECTIVES: To determine the effects of altered circadian rhythms on adipogenesis and to better understand how circadian and adipogenic regulatory pathways are linked, zebrafish larvae were exposed to various light/dark cycles or hypercaloric feeding (HCF). METHODS: Clock and adipogenic gene expression was quantitative real time PCR. Adipogenesis was characterized using coherent anti-Stokes Raman scattering microscopy (CARS) and whole-mount lipid composition was analyzed by gas chromatography. The clock protein Rev-erbα and the adipogenesis-regulating protein Pparγ were localized by immunohistochemistry. RESULTS: Zebrafish larvae exposed to continuous light (LL) had a sevenfold higher prevalence of adipocytes compared with control fish under a 14 h light and 10 h dark cycle. It was also significantly higher compared with that in HCF larvae with control light/dark cycle, which showed a 5.5-fold increase compared with control animals. Although total fatty acid content was unaffected, adipocyte lipid composition was altered in LL zebrafish. In contrast, shifting the onset and duration of the light periods did not affect adipogenesis or total fatty acid content. Gene expression analysis revealed effects of LL and HCF on circadian cyclicity, with increased expression of the clock gene period2 and altered circadian rev-erbα expression in LL larvae. Immunostaining revealed for the first time that Rev-erbα and Pparγ colocalize in adipocytes, which together with the gene expression analysis suggests interplay between Rev-erbα and Ppar isoforms. CONCLUSIONS: The amount of light, but not shifted light/dark cycles, affected adipogenesis and lipid composition, possibly due to increased period2 expression, which, in turn, enhances Rev-erbα-regulated gene expression. As the pparßδ promoter includes three Rev-erbα binding sites, we hypothesize that pparßδ may be a direct target that ultimately activates Pparγ.


Assuntos
Adipócitos/efeitos da radiação , Adipogenia/efeitos da radiação , Proteínas CLOCK/fisiologia , Ritmo Circadiano/efeitos da radiação , Luz , Obesidade/metabolismo , Obesidade/patologia , Adipócitos/citologia , Adipócitos/metabolismo , Adipogenia/fisiologia , Animais , Proteínas CLOCK/genética , Proliferação de Células/efeitos da radiação , Ritmo Circadiano/fisiologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos da radiação , Imuno-Histoquímica , Larva , Luz/efeitos adversos , Fotoperíodo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo , Peixe-Zebra
15.
Nutr Hosp ; 32(2): 545-55, 2015 Aug 01.
Artigo em Espanhol | MEDLINE | ID: mdl-26268082

RESUMO

The main function of the adipocyte is lipid storage when there is a positive energy balance and lipid release when there is and energy deficiency. One characteristic of obesity is an increase in the number and size of adipocytes, which implies pre adipocyte (PAD) differentiation. The adipose tissue (AT) has its origins in the prenatal stage and may continue to expand during adulthood from precursor cells since mature adipocytes cannot multiply by cell division. This study provide updates on the events that occur during the origin and differentiation of PAD, the factors involved in the regulation of adipogenesis and mechanisms that regulate physiological functions of AT.


La principal función de los adipocitos es el almacenamiento de lípidos cuando hay exceso de energía y la movilización de la misma cuando hay deficiencia. Una de las características de la obesidad es el aumento de la cantidad y el tamaño de los adipocitos, lo que implica la diferenciación de preadipocitos (PAD). El tejido adiposo (TA) tiene su origen en la etapa prenatal y puede seguir expandiéndose durante la vida adulta a partir de células precursoras, ya que los adipocitos maduros no pueden multiplicarse por división celular. El presente estudio proveerá información reciente de los eventos que se producen durante el origen y diferenciación de los PAD, así como los factores implicados en la regulación de la adipogénesis y los mecanismos que regulan las funciones fisiológicas del TA.


Assuntos
Adipogenia/efeitos dos fármacos , Adipogenia/efeitos da radiação , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/efeitos da radiação , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos da radiação , Diferenciação Celular , Metabolismo Energético , Humanos , Obesidade/metabolismo
16.
Orthod Craniofac Res ; 18 Suppl 1: 50-61, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25865533

RESUMO

OBJECTIVES: This study tested whether or not gene expression in human marrow stromal fibroblast (MSF) cells depends on light wavelength and energy density. MATERIALS AND METHODS: Primary cultures of isolated human bone marrow stem cells (hBMSC) were exposed to visible red (VR, 633 nm) and infrared (IR, 830 nm) radiation wavelengths from a light emitting diode (LED) over a range of energy densities (0.5, 1.0, 1.5, and 2.0 Joules/cm2) Cultured cells were assayed for cell proliferation, osteogenic potential, adipogenesis, mRNA and protein content. mRNA was analyzed by microarray and compared among different wavelengths and energy densities. Mesenchymal and epithelial cell responses were compared to determine whether responses were cell type specific. Protein array analysis was used to further analyze key pathways identified by microarrays. RESULT: Different wavelengths and energy densities produced unique sets of genes identified by microarray analysis. Pathway analysis pointed to TGF-beta 1 in the visible red and Akt 1 in the infrared wavelengths as key pathways to study. TGF-beta protein arrays suggested switching from canonical to non-canonical TGF-beta pathways with increases to longer IR wavelengths. Microarrays suggest RANKL and MMP 10 followed IR energy density dose-response curves. Epithelial and mesenchymal cells respond differently to stimulation by light suggesting cell type-specific response is possible. CONCLUSIONS: These studies demonstrate differential gene expression with different wavelengths, energy densities and cell types. These differences in gene expression have the potential to be exploited for therapeutic purposes and can help explain contradictory results in the literature when wavelengths, energy densities and cell types differ.


Assuntos
Fibroblastos/efeitos da radiação , Expressão Gênica/efeitos da radiação , Raios Infravermelhos , Luz , Células-Tronco Mesenquimais/efeitos da radiação , Adipogenia/efeitos da radiação , Técnicas de Cultura de Células , Linhagem Celular , Proliferação de Células/efeitos da radiação , Células Cultivadas , Cor , Relação Dose-Resposta à Radiação , Células Epiteliais/efeitos da radiação , Perfilação da Expressão Gênica , Humanos , Queratinócitos/efeitos da radiação , Metaloproteinase 10 da Matriz/efeitos da radiação , Células-Tronco Mesenquimais/fisiologia , Análise em Microsséries , Osteogênese/efeitos da radiação , Proteínas Proto-Oncogênicas c-akt/efeitos da radiação , Ligante RANK/efeitos da radiação , RNA Mensageiro/efeitos da radiação , Doses de Radiação , Transdução de Sinais/efeitos da radiação , Fator de Crescimento Transformador beta/efeitos da radiação
18.
Bioelectromagnetics ; 35(7): 519-30, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25196555

RESUMO

It was reported that obese (Ob/Ob) mice lose their weight and fat when treated with 0.5 T direct current electromagnetic fields. We also observed that 7.5 Hz, 0.4 T rotation of extremely low frequency magnetic fields (ELF-MF) has an inhibitory effect on obesity. Mesenchymal stem cells (MSCs) are multi-potent cells capable of differentiating to different MSC lineages, including adipose. We hypothesized that inhibitory effects of ELF-MF on obesity may be related to the differentiation of MSCs to adipocytes. In the present study, we investigated the effects of 7.5 Hz, 0.4 T ELF-MF on differentiation of human umbilical cord MSCs. We found that ELF-MF inhibited adipogenic differentiation (exposed 2 h/day for 15 days) of MSCs but had no effect on osteogenic differentiation (exposed 2 h/day for 21 days). Moreover, ELF-MF inhibited adipocyte-specific expression of peroxisome proliferator-activated receptor 2 (PPARγ2). ELF-MF promoted c-Jun N-terminal kinase (JNK)-dependent intracellular signaling in MSCs. Furthermore, activation of the non-canonical Wnt pathway provoked the inhibition of PPARγ2 expression resulting in suppression of adipogenic differentiation. In addition, the effects of ELF-MF on growth and apoptosis of MSCs were not observed. Our data indicated that ELF-MF of 7.5 Hz, 0.4 T inhibited the adipogenic differentiation of MSCs via JNK-dependent Wnt signaling pathway, but had no effect on the growth and function of MSCs, suggesting the inhibitory effect of ELF-MF on obesity may be attributed to the inhibition of differentiation of MSCs into adipocytes. This study may provide a potential approach for the treatment of obesity.


Assuntos
Adipogenia/efeitos da radiação , Campos Magnéticos/efeitos adversos , Células-Tronco Mesenquimais/efeitos da radiação , Osteogênese/efeitos da radiação , Adipogenia/fisiologia , Apoptose/efeitos da radiação , Western Blotting , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Citometria de Fluxo , Imunofluorescência , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Osteogênese/fisiologia , PPAR gama/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Cordão Umbilical/citologia , Cordão Umbilical/fisiologia , Cordão Umbilical/efeitos da radiação , Via de Sinalização Wnt/fisiologia , Via de Sinalização Wnt/efeitos da radiação
19.
Pharm Res ; 31(11): 2952-62, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24805277

RESUMO

PURPOSE: Cerium oxide nanoparticles (nanoceria, NC) have extraordinary antioxidant activity that made them suitable as a therapeutic agent for several diseases where reactive oxygen species (ROS) act by impairing the normal redox balance. Among different functions, it has been proven that ROS are cellular messengers involved in the adipogenesis: we thus investigated the implication of NC administration in the potential inhibition of adipogenic differentiation of mesenchymal stem cells (MSCs) used as a model of adipogenesis. METHODS: We evaluated cytotoxic effects and adipogenic maturation of mesenchymal stem cells following in vitro NC administration, both at gene and at phenotype level. RESULTS: Overall, our results demonstrated that NC efficiently inhibit the maturation of MSCs toward adipocytes owing to their ability to reduce the production of the ROS necessary during adipogenesis. CONCLUSIONS: These findings, even if preliminary, represent an important step toward the potential pharmaceutical application of NC in the treatment of obesity.


Assuntos
Adipogenia/efeitos da radiação , Cério/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas/administração & dosagem , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Ratos , Espécies Reativas de Oxigênio/metabolismo
20.
PLoS One ; 8(8): e73206, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24009740

RESUMO

DNA damage can lead to the induction of cellular senescence. In particular, we showed that exposure to ionizing radiation (IR) leads to the senescence of bone marrow-derived multipotent stromal cells (MSC) and osteoblast-like stromal cells (OB-SC), a phenotype associated with bone loss. The mechanism by which IR leads to bone dysfunction is not fully understood. One possibility involves that DNA damage-induced senescence limits the regeneration of bone progenitor cells. Another possibility entails that bone dysfunction arises from the inability of accumulating senescent cells to fulfill their physiological function. Indeed, we show here that exposure to IR prevented the differentiation and mineralization functions of MSC, an effect we found was limited to this population as more differentiated OB-SC could still form mineralize nodules. This is in contrast to adipogenesis, which was inhibited in both IR-induced senescent MSC and 3T3-L1 pre-adipocytes. Furthermore, we demonstrate that IR-induced loss of osteogenic potential in MSC was p53-dependent, a phenotype that correlates with the inability to upregulate key osteogenic transcription factors. These results are the first to demonstrate that senescence impacts osteogenesis in a cell type dependent manner and suggest that the accumulation of senescent osteoblasts is unlikely to significantly contribute to bone dysfunction in a cell autonomous manner.


Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteócitos/citologia , Osteócitos/metabolismo , Osteogênese/fisiologia , Proteína Supressora de Tumor p53/genética , Adipogenia/fisiologia , Adipogenia/efeitos da radiação , Animais , Diferenciação Celular/efeitos da radiação , Linhagem Celular , Linhagem da Célula/efeitos da radiação , Senescência Celular/efeitos da radiação , Células-Tronco Mesenquimais/efeitos da radiação , Camundongos , Osteogênese/efeitos da radiação , Radiação Ionizante , Proteína Supressora de Tumor p53/metabolismo
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