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1.
Int J Mol Sci ; 25(15)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39125748

RESUMO

Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) have been increasingly investigated for cancer therapy and drug delivery, and they offer an advanced cell-free therapeutic option. However, their overall effects and efficacy depend on various factors, including the MSC source and cargo content. In this study, we isolated EVs from the conditioned medium of human immature dental pulp stem cells (hIDPSC-EVs) and investigated their effects on two papillary thyroid cancer (PTC) cell lines (BCPAP and TPC1). We observed efficient uptake of hIDPSC-EVs by both PTC cell lines, with a notable impact on gene regulation, particularly in the Wnt signaling pathway in BCPAP cells. However, no significant effects on cell proliferation were observed. Conversely, hIDPSC-EVs significantly reduced the invasive capacity of both PTC cell lines after 120 h of treatment. These in vitro findings suggest the therapeutic potential of hIDPSC-EVs in cancer management and emphasize the need for further research to develop novel and effective treatment strategies. Furthermore, the successful internalization of hIDPSC-EVs by PTC cell lines underscores their potential use as nanocarriers for anti-cancer agents.


Assuntos
Proliferação de Células , Polpa Dentária , Vesículas Extracelulares , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Polpa Dentária/citologia , Vesículas Extracelulares/metabolismo , Câncer Papilífero da Tireoide/terapia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Linhagem Celular Tumoral , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Via de Sinalização Wnt , Meios de Cultivo Condicionados/farmacologia
2.
Biotechnol Lett ; 46(5): 907-924, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38900338

RESUMO

Mesenchymal stem/stromal cells (MSC) play a pivotal role in regenerative therapies. Recent studies show that factors secreted by MSC can replicate their biological activity, driving the emergence of cell-free therapy, likely to surpass stem cell therapy. Patents are an objective measure of R&D and innovation activities, and patent mapping allows us to verify the state of the art and technology, anticipate trends, and identify emerging lines of research. This review performed a search on Derwent World Patents Index™ and retrieved 269 patent families related to the MSC-derived cell-free products. Analysis reveals an exponential increase in patents from the mid-2010s, primarily focusing on exosomes. The patent's contents offer a great diversity of applications and associated technologies by using the products as medicinal agents or drug delivery systems. Nevertheless, numerous application branches remain unexplored, suggesting vast potential for cell-free technologies alone or combined with other approaches.


Assuntos
Células-Tronco Mesenquimais , Patentes como Assunto , Células-Tronco Mesenquimais/citologia , Humanos , Exossomos , Sistema Livre de Células , Medicina Regenerativa/métodos , Animais
3.
Int J Mol Sci, v. 25, n. 15, 8178, jul. 2024
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5455

RESUMO

Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) have been increasingly investigated for cancer therapy and drug delivery, and they offer an advanced cell-free therapeutic option. However, their overall effects and efficacy depend on various factors, including the MSC source and cargo content. In this study, we isolated EVs from the conditioned medium of human immature dental pulp stem cells (hIDPSC-EVs) and investigated their effects on two papillary thyroid cancer (PTC) cell lines (BCPAP and TPC1). We observed efficient uptake of hIDPSC-EVs by both PTC cell lines, with a notable impact on gene regulation, particularly in the Wnt signaling pathway in BCPAP cells. However, no significant effects on cell proliferation were observed. Conversely, hIDPSC-EVs significantly reduced the invasive capacity of both PTC cell lines after 120 h of treatment. These in vitro findings suggest the therapeutic potential of hIDPSC-EVs in cancer management and emphasize the need for further research to develop novel and effective treatment strategies. Furthermore, the successful internalization of hIDPSC-EVs by PTC cell lines underscores their potential use as nanocarriers for anti-cancer agents.

4.
World J Stem Cells ; 15(5): 453-465, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37342215

RESUMO

Extracellular vesicles (EVs) are nanometric particles that enclose cell-derived bioactive molecules in a lipid bilayer and serve as intercellular communication tools. Accordingly, in various biological contexts, EVs are reported to engage in immune modulation, senescence, and cell proliferation and differentiation. Therefore, EVs could be key elements for potential off-the-shelf cell-free therapy. Little has been studied regarding EVs derived from human pluripotent stem cells (hPSC-EVs), even though hPSCs offer good opportunities for induction of tissue regeneration and unlimited proliferative ability. In this review article, we provide an overview of studies using hPSC-EVs, focusing on identifying the conditions in which the cells are cultivated for the isolation of EVs, how they are characterized, and applications already demonstrated. The topics reported in this article highlight the incipient status of the studies in the field and the significance of hPSC-EVs' prospective applications as PSC-derived cell-free therapy products.

5.
Int Immunopharmacol ; 118: 110076, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37030123

RESUMO

Inflammatory bowel diseases (IBD), including ulcerative colitis, are chronic and idiopathic inflammations of the gastrointestinal tract. A disruption of the epithelial barrier and an imbalance between Th1 and Th2 subsets are associated with the onset and progression of these diseases. Mesenchymal stromal cells (MSC) are a promising therapy for IBD. However, cell-tracking studies have shown that intravenously infused MSC localize to the lungs and present short-term survival. To reduce practical complexities arising from living cells, we generated membrane particles (MP) from MSC membranes, which possess some of the immunomodulatory properties of MSC. This study investigated the effect of MSC-derived MP and conditioned media (CM) as cell-free therapies in the dextran sulfate sodium (DSS)-induced colitis model. Acute colitis was induced in C57BL/6 mice by oral administration of 2% DSS in drinking water ad libitum from days 0 to 7. Mice were treated with MP, CM, or living MSC on days 2 and 5. Our findings revealed that MP, CM, and living MSC ameliorated DSS-induced colitis by reducing colonic inflammation, the loss of colonic goblet cells, and intestinal mucosa permeability, preventing apoptosis of damaged colonic cells and balancing Th1 and Th2 activity. Therefore, MSC-derived MP have high therapeutic potential for treating IBD, overcoming the deficiencies of living MSC therapy, and opening novel frontiers in inflammatory diseases medicine.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Células-Tronco Mesenquimais , Animais , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Sulfato de Dextrana , Doenças Inflamatórias Intestinais/terapia , Colite/terapia , Colite/tratamento farmacológico , Colo , Inflamação , Meios de Cultivo Condicionados/farmacologia , Citocinas/uso terapêutico
6.
Cells ; 12(4)2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36831304

RESUMO

Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI.


Assuntos
Amiodarona , Doença Hepática Induzida por Substâncias e Drogas , Fígado Gorduroso , Células-Tronco Mesenquimais , Camundongos , Animais , Humanos , Tamoxifeno , Amiodarona/metabolismo , Secretoma , Camundongos Endogâmicos C57BL , Células-Tronco Mesenquimais/metabolismo , Fígado Gorduroso/metabolismo , Fatores Imunológicos/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo
7.
Front Cell Infect Microbiol ; 12: 980817, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467728

RESUMO

Extracellular vesicles (EVs) include a heterogeneous group of particles. Microvesicles, apoptotic bodies and exosomes are the most characterized vesicles. They can be distinguished by their size, morphology, origin and molecular composition. To date, increasing studies demonstrate that EVs mediate intercellular communication. EVs reach considerable interest in the scientific community due to their role in diverse processes including antigen-presentation, stimulation of anti-tumoral immune responses, tolerogenic or inflammatory effects. In pathogens, EV shedding is well described in fungi, bacteria, protozoan and helminths parasites. For Trypanosoma cruzi EV liberation and protein composition was previously described. Dendritic cells (DCs), among other cells, are key players promoting the immune response against pathogens and also maintaining self-tolerance. In previous reports we have demonstrate that T. cruzi downregulates DCs immunogenicity in vitro and in vivo. Here we analyze EVs from the in vitro interaction between blood circulating trypomastigotes (Tp) and bone-marrow-derived DCs. We found that Tp incremented the number and the size of EVs in cultures with DCs. EVs displayed some exosome markers and intracellular RNA. Protein analysis demonstrated that the parasite changes the DC protein-EV profile. We observed that EVs from the interaction of Tp-DCs were easily captured by unstimulated-DCs in comparison with EVs from DCs cultured without the parasite, and also modified the activation status of LPS-stimulated DCs. Noteworthy, we found protection in animals treated with EVs-DCs+Tp and challenged with T. cruzi lethal infection. Our goal is to go deep into the molecular characterization of EVs from the DCs-Tp interaction, in order to identify mediators for therapeutic purposes.


Assuntos
Doença de Chagas , Exossomos , Vesículas Extracelulares , Trypanosoma cruzi , Animais , Comunicação Celular , Doença de Chagas/terapia
8.
Front Bioeng Biotechnol ; 10: 882545, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35497332

RESUMO

Cancer is the second leading cause of death worldwide, with 10.0 million cancer deaths in 2020. Despite advances in targeted therapies, some pharmacological drawbacks associated with anticancer chemo and immunotherapeutic agents include high toxicities, low bioavailability, and drug resistance. In recent years, extracellular vesicles emerged as a new promising platform for drug delivery, with the advantage of their inherent biocompatibility and specific targeting compared to artificial nanocarriers, such as liposomes. Particularly, mesenchymal stem/stromal cells were proposed as a source of extracellular vesicles for cancer therapy because of their intrinsic properties: high in vitro self-renewal and proliferation, regenerative and immunomodulatory capacities, and secretion of extracellular vesicles that mediate most of their paracrine functions. Moreover, extracellular vesicles are static and safer in comparison with mesenchymal stem/stromal cells, which can undergo genetic/epigenetic or phenotypic changes after their administration to patients. In this review, we summarize currently reported information regarding mesenchymal stem/stromal cell-derived extracellular vesicles, their proper isolation and purification techniques - from either naive or engineered mesenchymal stem/stromal cells - for their application in cancer therapy, as well as available downstream modification methods to improve their therapeutic properties. Additionally, we discuss the challenges associated with extracellular vesicles for cancer therapy, and we review some preclinical and clinical data available in the literature.

9.
Cells ; 10(10)2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34685596

RESUMO

Cancer is one of the most important health problems and the second leading cause of death worldwide. Despite the advances in oncology, cancer heterogeneity remains challenging to therapeutics. This is because the exosome-mediated crosstalk between cancer and non-cancer cells within the tumor microenvironment (TME) contributes to the acquisition of all hallmarks of cancer and leads to the formation of cancer stem cells (CSCs), which exhibit resistance to a range of anticancer drugs. Thus, this review aims to summarize the role of TME-derived exosomes in cancer biology and explore the clinical potential of mesenchymal stem-cell-derived exosomes as a cancer treatment, discussing future prospects of cell-free therapy for cancer treatment and challenges to be overcome.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Exossomos/fisiologia , Neoplasias , Microambiente Tumoral , Antineoplásicos/uso terapêutico , Transição Epitelial-Mesenquimal , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Células-Tronco Neoplásicas
10.
Cells, v. 10, n. 10, 2617, out. 2021
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-3978

RESUMO

Cancer is one of the most important health problems and the second leading cause of death worldwide. Despite the advances in oncology, cancer heterogeneity remains challenging to therapeutics. This is because the exosome-mediated crosstalk between cancer and non-cancer cells within the tumor microenvironment (TME) contributes to the acquisition of all hallmarks of cancer and leads to the formation of cancer stem cells (CSCs), which exhibit resistance to a range of anticancer drugs. Thus, this review aims to summarize the role of TME-derived exosomes in cancer biology and explore the clinical potential of mesenchymal stem-cell-derived exosomes as a cancer treatment, discussing future prospects of cell-free therapy for cancer treatment and challenges to be overcome.

11.
Cells ; 9(12)2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322404

RESUMO

The aging population has contributed to the rapid rise in the global incidence of neurodegenerative diseases. Despite the medical advances, there are no effective treatments for these disorders. Therefore, there is an urgent need for new treatments for these diseases. In this sense, cell therapy has been recognized as the best candidate for treating incurable diseases, such as neurodegenerative disorders. However, the therapeutic use of these cells can be limited by several factors. Thus, there has been a rediscovery that extracellular vesicles, including exosomes, can be alternatively explored in the treatment of these diseases, overcoming the limits of cell-based therapy. In this sense, this review aims to revisit all areas from biology, including biogenesis and the content of exosomes, to biotechnology, proposing the minimal information required to isolate, characterize, and study the content of these vesicles for scientific and/or clinical purposes.


Assuntos
Exossomos/metabolismo , Doenças Neurodegenerativas/terapia , Biotecnologia , Meios de Cultivo Condicionados/química , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Exossomos/transplante , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Metaloproteases/metabolismo , Doenças Neurodegenerativas/patologia , Ácidos Nucleicos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Cells, v. 9, n. 12, 2663, dez. 2020
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-3415

RESUMO

The aging population has contributed to the rapid rise in the global incidence of neurodegenerative diseases. Despite the medical advances, there are no effective treatments for these disorders. Therefore, there is an urgent need for new treatments for these diseases. In this sense, cell therapy has been recognized as the best candidate for treating incurable diseases, such as neurodegenerative disorders. However, the therapeutic use of these cells can be limited by several factors. Thus, there has been a rediscovery that extracellular vesicles, including exosomes, can be alternatively explored in the treatment of these diseases, overcoming the limits of cell-based therapy. In this sense, this review aims to revisit all areas from biology, including biogenesis and the content of exosomes, to biotechnology, proposing the minimal information required to isolate, characterize, and study the content of these vesicles for scientific and/or clinical purposes.

13.
Neural Regen Res ; 14(9): 1626-1634, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31089063

RESUMO

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment. The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer's disease. Alzheimer's disease mouse models were established by injection of beta amyloid 1-42 aggregates into dentate gyrus bilaterally. Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration. Afterwards, neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies. Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1-42-induced cognitive impairment, and these effects are similar to those shown in the mesenchymal stem cells. These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer's disease. All procedures and experiments were approved by Institutional Animal Care and Use Committee (CICUAL) (approval No. CICUAL 2016-011) on April 25, 2016.

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