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1.
Zhonghua Shao Shang Za Zhi ; 35(9): 645-654, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594182

RESUMO

Objective: To investigate whether adipose-derived stem cells (ASCs) from allogeneic diabetic rats can promote wound healing in diabetic rats or not and the mechanism. Methods: (1) Fifty-six male Wistar rats aged 12-16 weeks were divided into diabetic group and healthy group according to the random number table (the same grouping method below), with 28 rats in each group. Rats in healthy group were not treated with any treatment. Rats in diabetic group were injected with 10 g/L streptozotocin 60 mg/kg intraperitoneally in one time to establish the diabetic model. Four rats in diabetic group and 4 rats in healthy group were selected according to the random number table, and the adipose tissue in the inguinal region was taken to culture and purify ASCs, so as to obtain healthy rat-derived ASCs (hereinafter referred to as nASCs) and diabetic rat-derived ASCs (hereinafter referred to as dASCs). The third passage of nASCs (n=3) and dASCs (n=3) were taken, and the positive expression rates of cell surface differentiation antigens CD105, CD31, CD34, and CD44 were detected with flow cytometer for defining ASCs purity. (2) The rest 24 rats in healthy group and 24 rats in diabetic group were used to make three round full-thickness skin defect wounds with a diameter of 12 mm on the back of each rat. Immediately after injury, phosphate buffer saline (PBS), nASCs of 2×10(7)/mL, and dASCs of 2×10(7)/mL each in the volume of 0.5 mL were subcutaneously injected into three wounds and their margins of each rat, respectively. On post injury day (PID) 1, 3, 7, and 12, 6 rats in each group were selected according to the random number table to calculate the wound area, and the wound tissue was stained with hematoxylin-eosin to observe the histological morphology of the wound. (3) Human ASCs (hASCs) were subcultured, and the 4th to 7th passage of cells were used for the subsequent experiments. The hASCs were divided into 7 groups, with 12 samples in each group. Cells in blank control group were cultured with mesenchymal stem cell culture medium, and cells in simple advanced glycation end products (AGEs) group, simple protein group, simple high glucose group, simple high osmotic pressure group, AGEs-high glucose combination group, and protein-high osmotic pressure combination group were cultured with mesenchymal stem cell culture medium containing a final mass concentration of 100 mg/L AGEs, 100 mg/L bovine serum albumin (BSA), 28 mmol/L D-glucose, 28 mmol/L mannitol, 100 mg/L AGEs+ 28 mmol/L D-glucose, 100 mg/L BSA+ 28 mmol/L mannitol, respectively. Cell proliferation was detected by cell counting kit 8 at post culture hour (PCH) 2 and on post culture day (PCD) 2, 4 and 6. (4) The hASCs were divided into blank control group, simple AGE group, simple high glucose group, and AGE-high glucose combination group, with 12 samples in each group, which were treated the same as corresponding groups in experiment (3). On PCD 0, 2, 4, and 6, the positive expression rates of cell surface differentiation antigens CD105, CD44, and CD45 were detected by flow cytometer to estimate their homeostasis. (5) The hASCs were divided into AGE-high glucose combination group and protein-high osmotic pressure combination group, with 9 samples in each group, which were treated the same as corresponding groups in experiment (3). On PCD 2, 4, and 6, the expression of intracellular protein was detected by cyanine 3-streptavidin double-antibody sandwich technique. Data were processed with analysis of variance for factorial design, least significant difference test, and Bonferroni correction. Results: (1) The positive expression rates of CD44 in nASCs and dASCs were both higher than 96%, the positive expression rates of CD31 and CD34 were low, and the positive expression rates of CD105 were about 40%, which basically met the purity requirements. (2) The areas of wounds treated by three methods in rats of healthy group and diabetic group were similar on PID 1 (P>0.05). In healthy group, compared with (0.682 1±0.078 9), (0.314 3±0.113 7), and (0.064 3±0.002 1) cm(2) of the PBS-treated wounds in rats, the area of nASCs-treated wounds in rats decreased significantly on PID 3, 7, and 12 [(0.464 1±0.092 6), (0.223 9±0.072 7), and (0.034 3±0.012 5) cm(2), P<0.05], the area of dASCs-treated wounds in rats decreased significantly on PID 3 and 12 [(0.514 1±0.124 1) and (0.043 7±0.032 8) cm(2), P<0.05] but was not obviously changed on PID 7 [(0.274 2±0.062 5) cm(2), P>0.05]. Compared with those of the dASCs-treated wounds of rats within the same group, the area of the nASCs-treated wounds of rats in healthy group decreased significantly on PID 3 and 7 (P<0.05) but was not obviously changed on PID 12 (P>0.05). In diabetic group, compared with (0.853 5±0.204 8), (0.670 5±0.164 8), and (0.131 4±0.074 4) cm(2) of the PBS-treated wounds in rats, the area of nASCs-treated wounds in rats decreased significantly on PID 3, 7, and 12 [(0.633 4±0.132 5), (0.331 8±0.023 5), and (0.074 2±0.003 8) cm(2), P<0.05], the area of dASCs-treated wounds in rats decreased significantly on PID 3 [(0.773 6±0.182 2) cm(2), P<0.05] but was not obviously changed on PID 7 and 12 [(0.510 6±0.192 2) and (0.114 4±0.003 1) cm(2), P>0.05]. Compared with the dASCs-treated wounds of rats within the same group, the area of the nASCs-treated wounds of rats in diabetic group was not obviously changed on PID 3 and 7 (P>0.05) but decreased significantly on PID 12 (P<0.05). There was no obvious difference in histological morphology of the wounds treated with three methods in rats of each group on PID 1. On PID 3, a small amount of microvessels were formed in the wounds treated with nASCs and dASCs of rats in both groups, but microvessel formation was almost undetected in the PBS-treated wounds. On PID 7, more small blood vessels and fibroblasts (Fbs) were observed in the wounds treated with nASCs and dASCs of rats in both groups, but the small blood vessels and Fbs were slightly less in the PBS-treated wounds. On PID 12, the wounds treated with nASCs and dASCs of rats in the two groups were covered by epithelial tissue, the granulation tissue in the PBS-treated wounds of rats in healthy group was not obvious, and the PBS-treated wounds of rats in diabetic group were not completely epithelialized. (3) Compared with those of blank control group, the cell number of hASCs in simple AGEs group decreased significantly on PCD 2, 4, and 6 (P<0.05), which increased significantly on PCD 2 and 4 in simple high glucose group (P<0.05), and that in AGEs-high glucose combination group decreased significantly on PCD 4 and 6 (P<0.05). (4) Compared with that on PCD 4 within the same group, the positive expression rate of CD105 in hASCs decreased significantly in blank control group, simple AGEs group, and AGEs-high glucose combination group on PCD 6 (P<0.05). The positive expression rate of CD44 was higher than 95%, and that of CD45 was less than 2% in hASCs of each group at each time point. (5) Detection values of 7 proteins were located in the confidence interval. The expression levels of basic fibroblast growth factor and tissue inhibitor of metalloproteinase-1 in hASCs of AGEs-high glucose combination group and protein-high osmotic pressure combination group showed increasing trend with the prolongation of culture time. The expression level of human monocyte chemoattractant protein 1 (MCP-1) in hASCs of AGEs-high glucose combination group showed increasing trend with the prolongation of culture time, while the expression level of growth-regulated oncogene (GRO) on PCD 6 was significantly higher than that on PCD 4 within the same group (P<0.05); the expression levels of MCP-1 and GRO in hASCs of protein-high osmotic pressure combination group showed decreasing trend with the prolongation of culture time. The expression level of follistatin in hASCs of protein-high osmotic pressure combination group decreased obviously on PCD 4, while that in hASCs of AGEs-high glucose combination group was significantly lower on PCD 6 than that on PCD 4 (P<0.05). The expression level of vascular endothelial growth factor (VEGF) in hASCs of protein-high osmotic pressure combination group decreased gradually with the prolongation of culture time, while that in hASCs of AGEs-high glucose combination group on PCD 4 decreased significantly as compared with that on PCD 2 (P<0.05). The expression level of urokinase-type plasminogen activator receptor in hASCs of protein-high osmotic pressure combination group on PCD 6 was significantly higher than that on PCD 4 within the same group (P<0.05) and that of AGEs-high glucose combination group on PCD 6 (P<0.05). Conclusions: Both nASCs and dASCs can promote wound healing in rats with simple defect injury, but dASCs have no significant effect on wound healing in rats with diabetes mellitus, which may be related to the inhibition of ASCs proliferation and the influence of high glucose and AGEs intervention on their homeostasis and secretory function.


Assuntos
Diabetes Mellitus Experimental/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Cicatrização , Tecido Adiposo/citologia , Animais , Células Cultivadas , Diabetes Mellitus Experimental/complicações , Humanos , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
2.
J Agric Food Chem ; 67(41): 11464-11473, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31532211

RESUMO

The intestinal epithelium is derived from intestinal stem cells (ISCs) and has direct contact with nutrients and toxins. However, whether methionine (Met) or a methionine hydroxyl analogue (2-hydroxy-4-(methylthio)butanoic acid (HMB)) can alleviate deoxynivalenol (DON)-induced intestinal injury remains unknown. Mice were treated orally with Met or HMB on days 1-11 and with DON on days 4-8. On day 12, the mice were sacrificed, and the jejunum was collected for crypt isolation and culture. Mouse enteroids were treated with DON and Met or HMB ex vivo. The results showed that Met and HMB increased the average daily feed intake and average daily gain of the mice. Met and HMB also improved the jejunal structure and barrier integrity and promoted ISC expansion, as indicated by the increased enteroid formation efficiency and area, under DON-induced injury conditions. In addition, DON-induced decreases in ISC activity were rescued Wnt/ß-catenin signaling reactivation by Met or HMB in vivo and ex vivo. Collectively, our findings reveal that Met and HMB alleviated DON-induced intestinal injury by improving ISC expansion and reactivating Wnt/ß-catenin signaling. Our study thus provides a nutritional intervention for intestinal diseases involving Wnt/ß-catenin signaling.


Assuntos
Enteropatias/tratamento farmacológico , Metionina/análogos & derivados , Metionina/administração & dosagem , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Tricotecenos/toxicidade , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Humanos , Enteropatias/genética , Enteropatias/metabolismo , Enteropatias/fisiopatologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/lesões , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Células-Tronco/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
3.
Life Sci ; 236: 116861, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513815

RESUMO

Osteoarthritis is a prevalent worldwide joint disease, which demonstrates a remarkable adverse effect on the patients' life modality. Medicinal agents, exclusively nonsteroidal anti-inflammatory drugs (NSAIDs), have been routinely applied in the clinic. But, their effects are restricted to pain control with insignificant effects on cartilage renovation, which would finally lead to cartilage destruction. In the field of regenerative medicine, many researchers have tried to use stem cells to repair tissues and other human organs. However, in recent years, with the discovery of extracellular microvesicles, especially exosomes, researchers have been able to offer more exciting alternatives on the subject. Exosomes and microvesicles are derived from different types of bone cells such as mesenchymal stem cells, osteoblasts, and osteoclasts. They are also recognized to play substantial roles in bone remodeling processes including osteogenesis, osteoclastogenesis, and angiogenesis. Specifically, exosomes derived from a mesenchymal stem cell have shown a great potential for the desired purpose. Exosomal products include miRNA, DNA, proteins, and other factors. At present, if it is possible to extract exosomes from various stem cells effectively and load certain products or drugs into them, they can be used in diseases, such as rheumatoid arthritis, osteoarthritis, bone fractures, and other diseases. Of course, to achieve proper clinical use, advances have to be made to establish a promising regenerative ability for microvesicles for treatment purposes in the orthopedic disorders. In this review, we describe the exosomes biogenesis and bone cell derived exosomes in the regenerate process of bone and cartilage remodeling.


Assuntos
Cartilagem Articular/citologia , Exossomos/transplante , Osteoartrite/terapia , Osteogênese , Células-Tronco/citologia , Humanos , Osteoartrite/complicações , Osteoartrite/patologia , Medicina Regenerativa
4.
Adv Exp Med Biol ; 1169: 55-62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487018

RESUMO

Sweat glands play an important role in skin physiology and are an integral part of the natural skin barrier. In order to maintain functionality throughout life, sweat glands make use of several types of stem cells. This chapter focuses on the classification of different types of stem cells found in the sweat gland and their physiological roles. First, sweat gland formation during skin maturation is addressed in order to give an overview of sweat gland origin and formation in vivo. Then, different kinds of adult sweat gland stem cells are introduced and classified between different potency levels and corresponding physiological roles. Finally, the importance of these cell sources for future developments, including applications in wound healing and cosmetics research, is discussed.


Assuntos
Células-Tronco , Glândulas Sudoríparas , Humanos , Pele/citologia , Pele/crescimento & desenvolvimento , Células-Tronco/citologia , Glândulas Sudoríparas/citologia , Cicatrização
5.
Adv Exp Med Biol ; 1169: 95-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487021

RESUMO

Epithelial stem cells reside within multiple regions of the lung where they renew various region-specific cells. In addition, there are multiple routes of regeneration after injury through built-in heterogeneity within stem cell populations and through a capacity for cellular plasticity among differentiated cells. These processes are important facets of respiratory tissue resiliency and organism survival. However, this regenerative capacity is not limitless, and repetitive or chronic injuries, environmental stresses, or underlying factors of disease may ultimately lead to or contribute to tissue remodeling and end-stage lung disease. This chapter will review stem cell heterogeneity among pulmonary epithelia in the lower respiratory system, discuss recent findings that may challenge long-held scientific paradigms, and identify several clinically relevant research opportunities for regenerative medicine.


Assuntos
Pulmão , Células-Tronco , Animais , Diferenciação Celular , Humanos , Pulmão/citologia , Células-Tronco/citologia
6.
Adv Exp Med Biol ; 1169: 119-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487022

RESUMO

Adult female mammals are endowed with the unique ability to produce milk for nourishing their newborn offspring. Milk is secreted on demand by the mammary gland, an organ which develops during puberty, further matures during pregnancy and lactation, but reverts to a resting state after weaning. The glandular tissue (re)generated through this series of structural and functional changes is finely sourced by resident stem cells under the control of systemic hormones and local stimuli.Over the past decades a plethora of studies have been carried out in order to identify and characterize mammary stem cells, primarily in mice and humans. Intriguingly, it is now emerging that multiple mammary stem cell pools (co)exist and are characterized by distinctive molecular markers and context-dependent functions.This chapter reviews the heterogeneity of the mammary stem cell compartment with emphasis on the key properties and molecular regulators of distinct stem cell populations in both the mouse and human glands.


Assuntos
Glândulas Mamárias Animais , Glândulas Mamárias Humanas , Células-Tronco , Animais , Diferenciação Celular , Feminino , Humanos , Lactação , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Humanas/citologia , Gravidez , Células-Tronco/citologia
7.
Adv Exp Med Biol ; 1169: 179-193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487024

RESUMO

Tissue-specific stem cells contribute to adult tissue maintenance, repair, and regeneration. In skeletal muscle, many different mononuclear cell types are capable of giving rise to differentiated muscle. Of these tissue stem-like cells, satellite cells (SCs) are the most studied muscle stem cell population and are widely considered the main cellular source driving muscle repair and regeneration in adult tissue. Within the satellite cell pool, many distinct subpopulations exist, each exhibiting differential abilities to exit quiescence, expand, differentiate, and self-renew. In this chapter, we discuss the different stem cell types that can give rise to skeletal muscle tissue and then focus on satellite cell heterogeneity during the process of myogenesis/muscle regeneration. Finally, we highlight emerging opportunities to better characterize muscle stem cell heterogeneity, which will ultimately deepen our appreciation of stem cells in muscle development, repair/regeneration, aging, and disease.


Assuntos
Músculo Esquelético , Células-Tronco , Adulto , Diferenciação Celular , Humanos , Desenvolvimento Muscular , Músculo Esquelético/citologia , Células-Tronco/citologia
8.
Yi Chuan ; 41(8): 686-702, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447420

RESUMO

Spermatogonial stem cells (SSCs) are male germline stem cells that reside in the basement membrane of the seminiferous tubule in the testis. SSCs are characterized by their capability of self-renewal to maintain the stem cell pool throughout the lifespan and commitments to germ line after puberty, thus transmitting the genetic information from parents to the SSC-derived progenies. SSCs can be isolated from testis, propagated in vitro, and induced to differentiate into varied germ cells. Although significant progress has been made in the field of rodent SSCs, the SSCs of large animals have advanced slowly. Studies on SSCs of large animal models can offer insights into the physiological and pathological mechanism of human reproduction. Moreover, SSCs of agricultural large animals can be used as an essential tool for multiplication of elite animal individuals, and generation of genetically modified livestock with valuable economic traits. In this review, we summarize the recent progress on SSCs of large animal models for agricultural and medical purposes, and discuss the present problems and future prospects. This review can give an overall view of large animal SSCs as respect to their applications in novel alternative reproductive technologies, generation of transgenic animals, treatment of male infertility and regenerative medicine.


Assuntos
Espermatogônias/citologia , Células-Tronco/citologia , Animais , Animais Geneticamente Modificados , Humanos , Infertilidade Masculina , Masculino , Modelos Animais , Testículo/citologia
9.
Adv Exp Med Biol ; 1165: 661-670, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399989

RESUMO

Renal failure is one of the most important causes of mortality and morbidity all over the world. Acute kidney injury (AKI) is a major clinical problem that affects up to 5% of all hospitalized patients. Although the kidney has a remarkable capacity for regeneration after acute injury, the mortality among patients with severe AKI remains dismally high, and in clinical practice, most patients cannot be cured completely and suffer from chronic kidney disease (CKD). Recently, the incidence and prevalence of CKD have increased, largely as a result of the enhanced prevalence of diabetes and obesity. The progressive nature of CKD and the ensuing end-stage renal disease (ESRD) place a substantial burden on global healthcare resources. Currently, dialysis and transplantation remain the only treatment options. Finding new therapeutic methods to fight AKI and CKD remains an ongoing quest. Although the human renal histological structure is complex, stem cell therapies have been applied to repair injured kidneys. The curative effects of mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), and nephron progenitor cells (NPCs) on renal repair have also been reported by researchers. This review focuses on stem cell therapy and mechanisms for renal injury repair.


Assuntos
Lesão Renal Aguda/terapia , Terapia Baseada em Transplante de Células e Tecidos , Células-Tronco/citologia , Humanos , Rim , Falência Renal Crônica/terapia , Néfrons , Insuficiência Renal Crônica/terapia
10.
Cytogenet Genome Res ; 158(3): 133-144, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31272101

RESUMO

Bone morphogenetic protein 2 (BMP2) can mediate the signaling of R-Smads and regulate different biological functions, including adipocyte differentiation. Long noncoding RNAs (lncRNAs) can be involved in many important biological processes, including fat metabolism, as miRNA sponges. This study aimed to investigate the molecular mechanism of fat deposition and to provide useful information for the prevention and treatment of lipid-related diseases. lncRNA sequencing was performed to compare and analyze, for the first time, the expression of lncRNAs in BMP2-induced and non-BMP2-induced preadipocytes from Junmu1 pigs. In addition, functional annotation and enrichment analysis of differentially expressed lncRNA target genes were carried out. lncRNAs and mRNAs were compared and analyzed. lncRNAs were identified that may regulate adipogenesis and lipid metabolism. The results give a theoretical basis for further studies on fat deposition mechanisms and provide potential therapeutic targets for metabolic diseases.


Assuntos
Adipócitos/efeitos dos fármacos , Proteína Morfogenética Óssea 2/farmacologia , Diferenciação Celular/efeitos dos fármacos , RNA Longo não Codificante/análise , Células-Tronco/efeitos dos fármacos , Suínos/genética , Transcriptoma/genética , Adipócitos/citologia , Adipócitos/metabolismo , Animais , RNA Longo não Codificante/genética , Análise de Sequência de RNA , Células-Tronco/citologia , Células-Tronco/metabolismo , Triglicerídeos/metabolismo
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(3): 291-299, 2019 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-31282321

RESUMO

Objective To induce adipose-derived stem cells (ADSCs) to differentiate into intermediate mesoderm (IM)-like cells in vitro,with IM-like cells for recellularizing kidney scaffolds,and then to obtain a tissue-engineering kidney with renal structures and functions through co-culture.Methods After inguinal fat pads of Wistar rats were surgically harvested,the primary ADSCs were isolated,induced,and cultured for stem cell identification. ADSCs were inducted to differentiate into IM-like cells by adding glycogen synthase kinase-3 inhibitor (CHIR99021) and fibroblast growth factor 9 (FGF9) at different stages. Seven days later,the IM-like cells were identified. The induced IM-like cells and well-prepared kidney decellularized scaffolds were co-cultured for 10 days to obtain recellularized tissue-engineered kidneys and their differentiation was identified.Results The ADSCs harvested had osteogenic and adipogenic abilities and could express the stem cell surface markers. After 7 days of in vitro induction,the positive expressions of odd-skipped related 1 and paired-box 2 were observed in IM-like cells by immunofluorescence technique. After 10 days of co-culture with kidney decellularized scaffolds,the positive expressions of Wilms'tumor 1,GATA-binding protein-3,and E-cadherin were observed by immunofluorescence technique.Conclusion ADSCs can be induced into IM-like cells,and renal cell differentiation can be observed through combining the induced IM-like cells with kidney decellularized scaffolds.


Assuntos
Rim/crescimento & desenvolvimento , Mesoderma/citologia , Regeneração , Células-Tronco/citologia , Engenharia Tecidual , Tecido Adiposo , Animais , Diferenciação Celular , Células Cultivadas , Ratos , Ratos Wistar , Tecidos Suporte
12.
Cell Mol Life Sci ; 76(20): 4043-4070, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31317205

RESUMO

Stem cells give rise to all cells and build the tissue structures in our body, and heterogeneity and plasticity are the hallmarks of stem cells. Epigenetic modification, which is associated with niche signals, determines stem cell differentiation and somatic cell reprogramming. Stem cells play a critical role in the development of tumors and are capable of generating 3D organoids. Understanding the properties of stem cells will improve our capacity to maintain tissue homeostasis. Dissecting epigenetic regulation could be helpful for achieving efficient cell reprograming and for developing new drugs for cancer treatment. Stem cell-derived organoids open up new avenues for modeling human diseases and for regenerative medicine. Nevertheless, in addition to the achievements in stem cell research, many challenges still need to be overcome for stem cells to have versatile application in clinics.


Assuntos
Epigênese Genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Organoides/metabolismo , Células-Tronco/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Diferenciação Celular , Transdiferenciação Celular , Reprogramação Celular , Transição Epitelial-Mesenquimal , Histonas/genética , Histonas/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Células-Tronco Neoplásicas/patologia , Organoides/patologia , Medicina Regenerativa/métodos , Nicho de Células-Tronco/genética , Transplante de Células-Tronco/métodos , Células-Tronco/classificação , Células-Tronco/citologia
13.
Int J Nanomedicine ; 14: 4709-4721, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308654

RESUMO

Objectives: Using dental Ti implants has become a well-accepted and used method for replacing missing dentition. It has become evident that in many cases peri-implant inflammation develops. The objective was to create and evaluate the antibacterial effect of silver nanoparticle (Ag-NP) coated Ti surfaces that can help to prevent such processes if applied on the surface of dental implants. Methods: Annealing I, Ag ion implantation by the beam of an Electron Cyclotron Resonance Ion Source (ECRIS), Ag Physical Vapor Deposition (PVD), Annealing II procedures were used, respectively, to create a safely anchored Ag-NP layer on 1x1 cm2 Grade 2 titanium samples. The antibacterial effect was evaluated by culturing Staphylococcus aureus (ATCC 29213) on the surfaces of the samples for 8 hours, and comparing the results to that of glass as control and of pure titanium samples. Alamar Blue assay was carried out to check cytotoxicity. Results: It was proved that silver nanoparticles were present on the treated surfaces. The average diameter of the particles was 58 nm, with a 25 nm deviation and Gaussian distribution, the the filling factor was 25%. Antibacterial evaluation revealed that the nanoparticle covered samples had an antibacterial effect of 64.6% that was statistically significant. Tests also proved that the nanoparticles are safely anchored to the titanium surface and are not cytotoxic. Conclusion: Creating a silver nanoparticle layer can be an option to add antibacterial features to the implant surface and to help in the prevention of peri-implant inflammatory processes. Recent studies demonstrated that silver nanoparticles can induce pathology in mammal cells, thus safe fixation of the particles is essential to prevent them from getting into the circulation.


Assuntos
Implantação Dentária/métodos , Nanopartículas Metálicas/química , Prata/farmacologia , Titânio/farmacologia , Animais , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Íons , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Staphylococcus aureus/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/ultraestrutura , Propriedades de Superfície
14.
Expert Opin Drug Saf ; 18(8): 651-677, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31268355

RESUMO

INTRODUCTION: Historically, drug development and marketing failures have been experienced by pharma organizations largely from insufficient human-predictability of biological data. AREAS COVERED: Organs-on-chips (OOCs) are emerging, cutting edge microphysiology systems for in vitro production of microengineered three-dimensional, miniature organotypic constructs obtained by cultivating small amounts of human primary, or induced pluripotent stem, cells in native-like microhabitats. These preparations circumvent experimental limitations inherent to animal assays and two-dimensional monolayers, the mainstay core biological assays of traditional drug research. This report reviews the fundamental tenets, key components (chip plate, biomaterials, cell differentiation approaches, and monitoring sensors) and issues concerning OOC systems (engineered top-down and bottom-up strategies for tissue/organ assembly, public aids to OOC development, regulatory validation, advantages, limitations, prospective and perspective of OOCs, ethics). Examples of OOC platforms (cancer-, lung-, blood-brain barrier-, heart-, intestine-, kidney-, liver-, pharmacokinetics-, placenta and vessel-on-chip) and their importance for drug research and development are presented. EXPERT OPINION: OOC device-generated bioconstructs hold great promise as experimental human tissue and organ platforms for generating human-pertinent knowledge on drug candidates for clinical assessment and reducing reliance on animal models. MPS technologies currently enable ready-to-assemble tissue patches and, hopefully, in coming decades, full-size, patient-personalized organs for regenerative medical interventions.


Assuntos
Desenvolvimento de Medicamentos/métodos , Dispositivos Lab-On-A-Chip , Modelos Biológicos , Alternativas aos Testes com Animais , Animais , Humanos , Pesquisa Farmacêutica/métodos , Células-Tronco/citologia
15.
Cell Biochem Funct ; 37(6): 452-458, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31318072

RESUMO

Autophagy is an evolutionarily conserved process that degrades and recycles defective organelles, toxic proteins, and various other aggregates on the cytoplasmic surface by sequestering them into autophagosomes which, then, fuse with lysosomes which degrade them. If these aggregates are not cleared, they accumulate and damage the cell resulting in cellular senescence and aging. Stem cells, with their capacity to differentiate, are crucial for tissue homeostasis. In addition to differentiation, the stemness of stem cells must be preserved. Recent studies in stem cells show the importance of autophagy in evading cellular senescence. In this review, we describe the conservative nature of the autophagy process, carried out throughout evolution. In particular, we highlight the role of autophagy in various evolutionarily diverse species and how it evolved to maintain tissue homeostasis and regulate aging and cellular senescence in stem cells.


Assuntos
Envelhecimento , Autofagia , Senescência Celular , Células-Tronco/citologia , Animais , Humanos
16.
Int J Nanomedicine ; 14: 4849-4866, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308662

RESUMO

Stem cells possess a promising potential in the clinical field. The application and effective delivery of stem cells to the desired target organ or site of injury plays an important role. This review describes strategies on understanding the effective delivery of stem cells labeled with superparamagnetic iron oxide nanoparticles (SPION) using an external magnet to enhance stem cell migration in vivo and in vitro. Fourteen total publications among 174 articles were selected. Stem cell type, SPION characteristics, labeling time, and magnetic force in vivo are considered important factors affecting the effective delivery of stem cells to the homing site. Most papers reported that the efficiency was increased when magnet is applied compared to those without. Ten studies analyzed the homing competency of SPION-labeled MSCs in vitro by observing the migration of the cell toward the external magnet. In cell-based experiments, the mechanism of magnetic attraction, the kind of nanoparticles, and various stem cells were studied well. Meta-analysis has shown the mean size of nanoparticles and degree of recovery or regeneration of damaged target organs upon in vivo studies. This strategy may provide a guideline for designing studies involving stem cell homing and further expand stem cell.


Assuntos
Magnetismo/métodos , Nanopartículas de Magnetita/química , Coloração e Rotulagem , Células-Tronco/metabolismo , Animais , Movimento Celular , Humanos , Hidrodinâmica , Tamanho da Partícula , Células-Tronco/citologia
17.
Cell Mol Life Sci ; 76(20): 4071-4102, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254043

RESUMO

Mammalian spermatogenesis is a highly complex multi-step process sustained by a population of mitotic germ cells with self-renewal potential known as spermatogonial stem cells (SSCs). The maintenance and regulation of SSC function are strictly dependent on a supportive niche that is composed of multiple cell types. A detailed appreciation of the molecular mechanisms underpinning SSC activity and fate is of fundamental importance for spermatogenesis and male fertility. However, different models of SSC identity and spermatogonial hierarchy have been proposed and recent studies indicate that cell populations supporting steady-state germline maintenance and regeneration following damage are distinct. Importantly, dynamic changes in niche properties may underlie the fate plasticity of spermatogonia evident during testis regeneration. While formation of spermatogenic colonies in germ-cell-depleted testis upon transplantation is a standard assay for SSCs, differentiation-primed spermatogonial fractions have transplantation potential and this assay provides readout of regenerative rather than steady-state stem cell capacity. The characterisation of spermatogonial populations with regenerative capacity is essential for the development of clinical applications aimed at restoring fertility in individuals following germline depletion by genotoxic treatments. This review will discuss regulatory mechanisms of SSCs in homeostatic and regenerative testis and the conservation of these mechanisms between rodent models and man.


Assuntos
Fertilidade/genética , Infertilidade Masculina/genética , Espermatogênese/genética , Espermatogônias/citologia , Células-Tronco/citologia , Testículo/citologia , Animais , Diferenciação Celular , Regulação da Expressão Gênica , Homeostase/genética , Humanos , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Infertilidade Masculina/terapia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Modelos Genéticos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Espermatogônias/metabolismo , Nicho de Células-Tronco/genética , Células-Tronco/metabolismo , Testículo/metabolismo
18.
Nat Cell Biol ; 21(6): 710-720, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31160709

RESUMO

The capacity of stem cells to self-renew or differentiate has been attributed to distinct metabolic states. A genetic screen targeting regulators of mitochondrial dynamics revealed that mitochondrial fusion is required for the maintenance of male germline stem cells (GSCs) in Drosophila melanogaster. Depletion of Mitofusin (dMfn) or Opa1 led to dysfunctional mitochondria, activation of Target of rapamycin (TOR) and a marked accumulation of lipid droplets. Enhancement of lipid utilization by the mitochondria attenuated TOR activation and rescued the loss of GSCs that was caused by inhibition of mitochondrial fusion. Moreover, constitutive activation of the TOR-pathway target and lipogenesis factor Sterol regulatory element binding protein (SREBP) also resulted in GSC loss, whereas inhibition of SREBP rescued GSC loss triggered by depletion of dMfn. Our findings highlight a critical role for mitochondrial fusion and lipid homeostasis in GSC maintenance, providing insight into the potential impact of mitochondrial and metabolic diseases on the function of stem and/or germ cells.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Membrana/genética , Dinâmica Mitocondrial/genética , Células-Tronco/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/genética , Animais , Diferenciação Celular/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Homeostase , Metabolismo dos Lipídeos/genética , Masculino , Mitocôndrias/genética , Receptores Proteína Tirosina Quinases/genética , Transdução de Sinais/genética , Nicho de Células-Tronco/genética , Células-Tronco/citologia , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
19.
Nat Commun ; 10(1): 2549, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186409

RESUMO

Human adipose tissue (hAT) is constituted of structural units termed lobules, the organization of which remains to be defined. Here we report that lobules are composed of two extracellular matrix compartments, i.e., septa and stroma, delineating niches of CD45-/CD34+/CD31- progenitor subsets characterized by MSCA1 (ALPL) and CD271 (NGFR) expression. MSCA1+ adipogenic subset is enriched in stroma while septa contains mainly MSCA1-/CD271- and MSCA1-/CD271high progenitors. CD271 marks myofibroblast precursors and NGF ligand activation is a molecular relay of TGFß-induced myofibroblast conversion. In human subcutaneous (SC) and visceral (VS) AT, the progenitor subset repartition is different, modulated by obesity and in favor of adipocyte and myofibroblast fate, respectively. Lobules exhibit depot-specific architecture with marked fibrous septa containing mesothelial-like progenitor cells in VSAT. Thus, the human AT lobule organization in specific progenitor subset domains defines the fat depot intrinsic capacity to remodel and may contribute to obesity-associated cardiometabolic risks.


Assuntos
Tecido Adiposo/anatomia & histologia , Tecido Adiposo/citologia , Nicho de Células-Tronco , Células-Tronco/citologia , Adipócitos/metabolismo , Adipogenia , Fosfatase Alcalina , Diferenciação Celular , Matriz Extracelular , Humanos , Gordura Intra-Abdominal/citologia , Miofibroblastos/citologia , Miofibroblastos/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Obesidade , Receptores de Fator de Crescimento Neural/metabolismo , Células-Tronco/metabolismo , Gordura Subcutânea/citologia , Fator de Crescimento Transformador beta1/farmacologia
20.
Mol Biol (Mosk) ; 53(3): 497-501, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31184615

RESUMO

Homeodomain transcription factors play a significant role in adipocyte differentiation. The role of Pbx1 and Prep1, proteins of the TALE family (the three amino acid loop extension), was previously established in adipocyte differentiation of mesenchymal stromal cells and 3T3-L1 cell line. In this study, with the use of RNA interference technology we show that another transcription factor from the same family, Meis1, which is a core protein of mature cardiomyocytes, represses adipogenesis to a greater degree than its paralog Meis2. A number of Meis target genes, markers of adipocytes, are identified. This may indicate the transcriptional mechanism of the effect of Meis1 on the adipocyte differentiation of mouse preadipocytes.


Assuntos
Adipócitos/citologia , Diferenciação Celular , Proteína Meis1/metabolismo , Miócitos Cardíacos/metabolismo , Adipócitos/metabolismo , Animais , Diferenciação Celular/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Células-Tronco/citologia , Células-Tronco/metabolismo
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