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1.
Kidney Int ; 99(1): 22-24, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33390229

RESUMO

Recent advances in material engineering and gene editing techniques have now made it possible to use sheeted stem cells as distributors of therapeutic factors in clinical practice (e.g., as beating sheets for patients with heart failure). In this issue, Park et al. report the effects of sheets of genome-engineered human umbilical cord-derived mesenchymal stem cells in preserving kidney function after ischemia-reperfusion injury, demonstrating a possible application for acute kidney injury treatment.


Assuntos
Lesão Renal Aguda , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismo por Reperfusão , Lesão Renal Aguda/terapia , Animais , Humanos , Traumatismo por Reperfusão/terapia , Cordão Umbilical
2.
Arthroscopy ; 37(1): 359-361, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33384092

RESUMO

The efficacy of mesenchymal stem cells regarding clinical outcomes and cartilage regeneration in knee osteoarthritis remains unclear; however, their theoretical role in multilineage cellular differentiation and immunomodulation of the arthritic cascade has been investigated. Several studies have reported that the use of stem cell therapy for knee osteoarthritis helps in pain improvement, but its effect on cartilage regeneration has not yet been explored. Moreover, numerous studies have reported high heterogeneity in the cell sources, as well as methods of culture expansion or cell concentration, and differences in delivery methods, assessment tools, and concomitant surgical procedures, which could affect the clinical outcomes or evaluation of cartilage regeneration potency. Furthermore, future studies are warranted to examine these factors in detail to interpret the results of mesenchymal stem cell treatment for knee osteoarthritis.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite do Joelho , Cartilagem , Humanos , Injeções Intra-Articulares , Osteoartrite do Joelho/terapia , Manejo da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Regeneração
3.
Arthroscopy ; 37(1): 379-380, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33384093

RESUMO

Mesenchymal stem cells (MSCs) have been investigated for the treatment of knee osteoarthritis because of their unique properties, including self-renewal, multi-linear cellular differentiation, and immunomodulatory capacity. However, the efficacy of MSCs for positive clinical outcomes in the treatment of knee osteoarthritis remains controversial. Because clinical studies in general have high variability, the heterogeneity in the sources of the stem cells used, efficacy of delivery methods, and concomitant surgery should be carefully considered to interpret the benefits of MSC therapy for knee osteoarthritis.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite do Joelho , Humanos , Injeções Intra-Articulares , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia
4.
Environ Sci Pollut Res Int ; 28(2): 2019-2030, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32865681

RESUMO

Liver fibrosis occurs in most types of chronic liver diseases and can develop into cirrhosis and liver failure. Bone marrow-derived mesenchymal stem cells (BMSCs) showed promising effects in the treatment of fibrosis. This study evaluated the possible role of Nrf2/HO-1 signaling in the ameliorative effect of BMSCs against carbon tetrachloride (CCl4)-induced liver fibrosis, oxidative stress, and inflammation in rats. Hepatic fibrosis was induced by subcutaneous injection of CCl4 twice per week for 6 consecutive weeks and rat BMSCs were administered intravenously. After 4 weeks, the rats were sacrificed, and samples were collected for analysis. CCl4-intoxicated rats showed elevated serum transaminases, ALP, γGT, bilirubin and pro-inflammatory cytokines, and decreased albumin. Hepatic NF-κB p65 and malondialdehyde (MDA) were significantly increased, and cellular antioxidants were decreased in CCl4-intoxicated rats. BMSCs ameliorated liver function markers, suppressed MDA, NF-κB p65, and inflammatory cytokines, and enhanced antioxidants in the liver of CCl4-intoxicated rats. BMSCs were engrafted within the liver tissue and prevented histological alterations and collagen accumulation induced by CCl4. In addition, BMSCs upregulated hepatic Nrf2 and HO-1 expression in CCl4-intoxicated rats. In conclusion, this study provides evidence that BMSCs suppress oxidative stress, inflammation, and liver fibrosis through a mechanism involving activation of the Nrf2/HO-1 signaling.


Assuntos
Células-Tronco Mesenquimais , Fator 2 Relacionado a NF-E2 , Animais , Tetracloreto de Carbono , Inflamação/metabolismo , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
5.
Chem Phys Lipids ; 234: 105009, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33189639

RESUMO

There are no commercially available effective antiviral medications or vaccines to deal with novel coronavirus disease (COVID-19). Hence there is a substantial unmet medical need for new and efficacious treatment options for COVID-19. Most COVID-19 deaths result from acute respiratory distress syndrome (ARDS). This virus induces excessive and aberrant inflammation so it is important to control the inflammation as soon as possible. To date, results of numerous studies have been shown that mesenchymal stem cells and their derivatives can suppress inflammation. Exosomes function as intercellular communication vehicles to transfer bioactive molecules (based on their origins), between cells. In this review, the recent exosome-based clinical trials for the treatment of COVID-19 are presented. Potential therapy may include the following items: First, using mesenchymal stem cells secretome. Second, incorporating specific miRNAs and mRNAs into exosomes and last, using exosomes as carriers to deliver drugs.


Assuntos
/terapia , Sistemas de Liberação de Medicamentos/métodos , Exossomos/transplante , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais , Antivirais/administração & dosagem , Antivirais/uso terapêutico , /imunologia , Ensaios Clínicos como Assunto , Exossomos/química , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Resultado do Tratamento
6.
Biochim Biophys Acta Mol Basis Dis ; 1867(2): 166014, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33232817

RESUMO

The coronavirus disease 2019 (COVID-19) has been threatening the globe since the end of November 2019. The disease revealed cracks in the health care system as health care providers across the world were left without guidelines on definitive usage of pharmaceutical agents or vaccines. The World Health Organization (WHO) declared COVID-19 as a pandemic on the 11th of March 2020. Individuals with underlying systemic disorders have reported complications, such as cytokine storms, when infected with the virus. As the number of positive cases and the death toll across the globe continue to rise, various researchers have turned to cell based therapy using stem cells to combat COVID-19. The field of stem cells and regenerative medicine has provided a paradigm shift in treating a disease with minimally invasive techniques that provides maximal clinical and functional outcome for patients. With the available evidence of immunomodulatory and immune-privilege actions, mesenchymal stem cells (MSCs) can repair, regenerate and remodulate the native homeostasis of pulmonary parenchyma with improved pulmonary compliance. This article revolves around the usage of novel MSCs therapy for combating COVID-19.


Assuntos
/epidemiologia , Síndrome da Liberação de Citocina/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Pandemias , /imunologia , /imunologia , Síndrome da Liberação de Citocina/epidemiologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/patologia
7.
Hum Cell ; 34(1): 1-13, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33033884

RESUMO

The COVID-19 pandemic has placed an unprecedented burden on health care systems and economies around the globe. Clinical evidences demonstrate that SARS-CoV-2 infection produces detrimental levels of pro-inflammatory cytokines and chemokines that can lead to acute respiratory distress syndrome (ARDS) and significant systemic organ damage. Currently, there is no definitive therapy for COVID-19 or associated complications, and with the hope of a safe and effective vaccine in the distant future, the search for an answer is paramount. Mesenchymal stem cells (MSCs) provide a viable option due to their immunomodulatory effects and tissue repair and regeneration abilities. Studies have demonstrated that compassionate use of MSCs can reduce symptoms associated with SARS-CoV-2 infection, eliminate fluid buildup, and act as a regenerative technique for alveolar damage; all in a safe and effective way. With multiple autologous sources available for MSCs, each with their own respective limitations, allogenic umbilical cord (UC) and/or UC-derived Wharton's jelly (WJ) seem to be best positioned source to harvest MSCs to treat COVID-19 and associated symptoms. As an allogenic source, UC is readily available, easily obtainable, and is rich in immunomodulatory and regenerative factors. In this manuscript, we reviewed the current evidences and explored the potential therapeutic use of allogenic UC and/or WJ-derived MSCs for the treatment of COVID-19. Although, preliminary preclinical and clinical studies indicate that their use is safe and potentially effective, more multi-center, randomized, controlled trials are needed to adequately assess the safety and efficacy of UC and/or WJ-derived MSCs for the treatment of COVID-19.


Assuntos
/terapia , Transplante de Células-Tronco Mesenquimais , Cordão Umbilical/citologia , Geleia de Wharton/citologia , Ensaios Clínicos como Assunto , Humanos , Imunomodulação , Células-Tronco Mesenquimais , Pandemias , /virologia
8.
Lab Med ; 52(1): 24-35, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-32729620

RESUMO

The COVID-19 pandemic has led to a major setback in both the health and economic sectors across the globe. The scale of the problem is enormous because we still do not have any specific anti-SARS-CoV-2 antiviral agent or vaccine. The human immune system has never been exposed to this novel virus, so the viral interactions with the human immune system are completely naive. New approaches are being studied at various levels, including animal in vitro models and human-based studies, to contain the COVID-19 pandemic as soon as possible. Many drugs are being tested for repurposing, but so far only remdesivir has shown some positive benefits based on preliminary reports, but these results also need further confirmation via ongoing trials. Otherwise, no other agents have shown an impactful response against COVID-19. Recently, research exploring the therapeutic application of mesenchymal stem cells (MSCs) in critically ill patients suffering from COVID-19 has gained momentum. The patients belonging to this subset are most likely beyond the point where they could benefit from an antiviral therapy because most of their illness at this stage of disease is driven by inflammatory (over)response of the immune system. In this review, we discuss the potential of MSCs as a therapeutic option for patients with COVID-19, based on the encouraging results from the preliminary data showing improved outcomes in the progression of COVID-19 disease.


Assuntos
/patologia , Síndrome da Liberação de Citocina/prevenção & controle , Transplante de Células-Tronco Mesenquimais/métodos , /patogenicidade , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , /mortalidade , Estado Terminal , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Progressão da Doença , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
9.
Life Sci ; 265: 118821, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33275988

RESUMO

Liver regeneration after partial hepatectomy (PH) is a complex and well-orchestrated process involving multiple factors such as cytokines, growth factors, and signaling pathways. MicroRNAs (miRNAs) participate in various biological processes including liver regeneration after PH. In the current study, we investigated the expression and function of human umbilical cord blood mesenchymal stem cell (hUCB-MSC) derived exosomal miRNAs on liver regeneration using a rat PH model. We found that hUCB-MSC derived exosomes promoted rat liver regeneration and ameliorated liver injury after PH. MicroRNA microarray was performed to identify the differentially expressed miRNAs in hUCB-MSC derived exosomes involving in liver regeneration after PH. We demonstrated that hUCB-MSC derived exosomal miR-124 could promote liver regeneration and prevent against liver injury after PH in rats. Inhibition of miR-124 abrogated the protective role of hUCB-MSC derived exosome in rat liver regeneration after PH. In addition, we identified that transcription factor Foxg1 was a direct target of miR-124 and miR-124 promoted rat liver cell proliferation via suppressing Foxg1 expression. Furthermore, we demonstrated that hUCB-MSC derived exosomal miR-124 enhanced liver regeneration via inhibiting Foxg1 in rats after PH. In summary, our findings suggest that hUCB-MSC-derived exosomal miR-124 could promote rat liver regeneration after PH via downregulating Foxg1.


Assuntos
Hepatectomia , Regeneração Hepática/genética , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Animais , Proliferação de Células/genética , Regulação para Baixo , Exossomos/metabolismo , Sangue Fetal/citologia , Humanos , Regeneração Hepática/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genética
10.
Life Sci ; 265: 118861, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33301811

RESUMO

AIMS: LncRNAs are involved in many biological processes, and hypoxia contributed to the alterations of lncRNAs. Hypoxic preconditioned olfactory mucosa mesenchymal stem cells (OM-MSCs) exerted stronger anti-apoptotic ability in models of disease, but the molecules that controlled different biological characteristics of human OM-MSCs between hypoxic and normoxic conditions were unclear. The present study was aimed to explore the molecules that controlled different biological characteristics of human OM-MSCs between hypoxic and normoxic conditions. MAIN METHODS: LncRNAs and mRNAs expression profiles of human OM-MSCs between hypoxic (3%) and normoxic conditions were analyzed by Next-Generation Sequencing (NGS) analysis, bioinformatics analysis on these data were further performed. Moreover, loss-of function assay was conducted to investigate the impact of hypoxic condition on the proliferation and apoptosis of OM-MSCs. KEY FINDINGS: Through the comparative analysis and bioinformatics analysis, a total of 1741 lncRNAs and 1603 mRNAs were significant differentially expressed in the hypoxia group compared with normoxia group. Enrichment analysis revealed that differentially expressed genes of human OM-MSCs mainly participated in cell cycle regulation, secretin of cytokines and so on. Meanwhile, hypoxic condition significantly promoted proliferation and inhibited apoptosis of human OM-MSCs, following loss-of-function assays confirmed that lncRNA DARS-AS1 were involved in this regulatory process by hypoxic condition. Further prediction of targeted genes and the construction of lncRNA-miRNA-mRNA interaction network enriched the significance regarding the mechanism of DARS-AS1. SIGNIFICANCE: Altogether, these findings provided a new perspective for understanding the molecules expression patterns in hypoxia that contributed to corresponding phenotype alterations of OM-MSCs.


Assuntos
Proliferação de Células/fisiologia , Células-Tronco Mesenquimais/citologia , Mucosa Olfatória/citologia , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Apoptose/fisiologia , Hipóxia Celular/fisiologia , Células Cultivadas , Regulação da Expressão Gênica , Humanos , MicroRNAs/genética
11.
Curr Opin Crit Care ; 27(1): 20-28, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278121

RESUMO

PURPOSE OF REVIEW: Advances in our understanding of the pathophysiology and biology of ARDS has identified a number of promising cellular and pharmacological therapies. These emerging therapeutics can modulate the immune response, reduce epithelial injury, target endothelial and vascular dysfunction, have anticoagulant effects, and enhance ARDS resolution. RECENT FINDINGS: Mesenchymal stromal cell therapy shows promise in earlier phase clinical testing, whereas a number of issues regarding clinical translation, such as donor and effect variability, are currently being optimized to enable larger scale clinical trials. Furthermore, a number of promising mesenchymal stromal cell therapy clinical studies for COVID-19-induced ARDS are underway. Recent studies provide support for several emerging ARDS pharmacotherapies, including steroids, statins, vitamins, anticoagulants, interferons, and carbon monoxide. The history of unsuccessful clinical trials of potential therapies highlights the challenges to successful translation for this heterogeneous clinical syndrome. Given this, attention has focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies, i.e. 'precision medicines'. SUMMARY: Mesenchymal stromal cells, steroids, statins, vitamins, anticoagulants, interferons and carbon monoxide have therapeutic promise for ARDS. Identifying ARDS sub-populations most likely to benefit from targeted therapies may facilitate future advances.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Células-Tronco Mesenquimais , /complicações , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , /tratamento farmacológico
12.
Life Sci ; 264: 118502, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33031825

RESUMO

Bone tissue engineering compasses the use of mesenchymal stem cells (MSCs) along with engineered biomaterial construct to augment bone regeneration. Till now, MSCs were isolated from various sources and used in cellular constructs. For the first time, in this study, MSCs were isolated from human Ovarian Follicular Fluid (OFF) and characterized by CD 44+ and CD 105+ markers via confocal microscopy and flow cytometry. Additionally, MSCs stemness, proliferation and colony-forming unit ability, multi-lineage differentiation potential were also studied. To test its suitability for bone tissue engineering applications, we grew the MSCs with the conditioned medium obtained from biocomposite scaffold by fusing a natural polymer, Chitosan (CS) and a synthetic polymer, Polycaprolactone (PCL) and the scaffold were coated with Zinc divalent ions to impart osteogenic properties. The physico-chemical characterization of scaffold, such as FTIR, XRD, and SEM studies was carried out. The biological characterization showed that the scaffolds were compatible with MSCs and promoted osteoblast differentiation which was confirmed at both cellular and molecular levels. The cellular construct increased calcium deposition, analyzed by alizarin red staining and ALP activity at cellular level. At the molecular level, the osteoblast markers expression such as Runx2 and type 1 collagen mRNAs, and osteonectin (ON) and osteocalcin (OC) secretory proteins were increased in the presence of scaffold. Overall, the current study recommends that MSCs can be easily obtained from human waste OFF, and grown in standard in vitro conditions. Successful growth of such MSCs with CS/PCL/Zn scaffold opens new avenues in utilizing the cell source for bone tissue engineering.


Assuntos
Materiais Biocompatíveis , Regeneração Óssea/fisiologia , Líquido Folicular/fisiologia , Folículo Ovariano/fisiologia , Engenharia Tecidual/métodos , Tecidos Suporte , Adulto , Materiais Biocompatíveis/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/citologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Células Cultivadas , Quitosana/administração & dosagem , Feminino , Líquido Folicular/citologia , Líquido Folicular/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais , Recuperação de Oócitos/métodos , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Folículo Ovariano/efeitos dos fármacos , Poliésteres/administração & dosagem , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos , Zinco/administração & dosagem
13.
Life Sci ; 264: 118684, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129877

RESUMO

AIMS: Fracture site is regionally hypoxic resulting from vasculature disruption. HIF-1αplays an essential role in fracture repair. This study aims to investigate the influence of FG4592 on the femur fracture of SD rats and the proliferation, migration of BMSCs. MATERIALS AND METHODS: After the femoral fracture model was established, computed tomography imaging and histological analyses were used to quantify bone healing and the expression of CD90, HIF-1α, VEGF were observed by means of immunohistochemistry method on Day 10 and Day 20. In addition, CCK-8 assay, transwell, flow cytometric analysis, laser confocal microscopy assay, western blot and rT-PCR were performed to text the proliferation and migration of BMSCs using FG4592. KEY FINDINGS: In vivo, FG4592 facilitated the repair of bone fracture by increasing the number of BMSCs and cartilage formation. In vitro, FG4592 markedly improved the proliferation, migration of BMSCs via upregulation of intracellular Ca2+, NO and concomitant decrease of ROS. Gene silencing of HIF-1α resulted in the opposite phenomenon in BMSCs with the treatment of FG4592. SIGNIFICANCE: The transplantation of BMSCs is the most promising candidate for the treatment of fracture non-union. We illustrated that FG4592 promoted the proliferation, migration of BMSCs via the HIF/Ca2+/NO/ROS pathway and further accelerated fracture healing. These results provide a deeper understanding for the mechanism of HIF in promoting fracture healing.


Assuntos
Fraturas do Colo Femoral/metabolismo , Glicina/análogos & derivados , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoquinolinas/uso terapêutico , Transplante de Células-Tronco Mesenquimais/métodos , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Células da Medula Óssea/metabolismo , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/terapia , Consolidação da Fratura/efeitos dos fármacos , Consolidação da Fratura/fisiologia , Glicina/farmacologia , Glicina/uso terapêutico , Isoquinolinas/farmacologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley
14.
Chem Biol Interact ; 333: 109324, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33212048

RESUMO

Recent evidence has shown that mesenchymal stem cells (MSCs) play vital roles in cell therapy of ischemia/hypoxia damaged tissues. However, after the transplantation, they might undergo apoptosis due to oxidative stress. Thus, some strategies have been developed to support stem cells in harsh conditions, including pre-treatment of the cells with antioxidants. Of various antioxidants, in this study, astaxanthin (ATX) was used to protect adipose-derived MSCs against oxidative stress. The MSCs were exposed to different doses of hydrogen peroxide, and then the expression of key genes involved in the redox signaling pathway was studied, including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH quinine oxidoreductase 1 (NQO1). The balance of intracellular reactive oxygen species was detected with the H2DCFDA molecular probe. Additionally, for the detection of apoptosis and protective effect of ATX, the DAPI/Phallacidin and annexin V cell staining were performed. The results of cellular studies revealed that ATX reduced the H2O2-induced cell apoptosis and oxidative stress. Furthermore, after the induction of oxidative stress, the cells' native antioxidants (HO-1 and NQO1) were overexpressed but they were modulated with ATX treatments (p < 0.023). Based on our findings, ATX could increase the expression of Nrf2 as a key transcription factor of antioxidant enzymes (p < 0.05). These findings support the notion that ATX can act as an effective antioxidant in the pre-treatment of MSCs before cell therapy. Thus, to enhance the viability of stem cells during the transplantation in harsh conditions, the concurrent use of ATX in cell therapy modalities is proposed.


Assuntos
Citoproteção/efeitos dos fármacos , Depuradores de Radicais Livres/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tecido Adiposo/citologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/farmacologia
15.
Life Sci ; 264: 118658, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33115604

RESUMO

Sepsis occurs due to a damaging host response to infection and is the chief cause of death in most intensive care units. Mesenchymal stem cells (MSCs) exhibit immunomodulatory properties and can modulate key cells of the innate and adaptive immune systems through various effector mechanisms, such as exosomes. Exosomes and their microRNA (miRNA or miR) cargo including miR-21 can initiate profound phenotypic changes in the tumor microenvironment due to their intercellular communication transmitting the pleiotropic messages between different cell types, tissues, and body fluids. Here, we aimed to characterize the effect of miR-21 delivered from MSC-derived exosomes on the polarization of macrophages in a mouse sepsis model. First, we isolated exosomes from interleukin-1ß (IL-1ß)-pretreated murine MSCs (ßMSCs) and injected them into cecal ligation and puncture (CLP) septic models. We found that ßMSCs-derived exosomes could more effectively induce M2-like polarization of macrophages in vitro and in vivo. Administration of ßMSCs-derived exosomes attenuated the symptoms in septic mice more effectively and increased their survival rate as compared to exosomes released by naïve MSCs. Importantly, we found that miR-21 was abundantly upregulated in MSCs upon IL-1ß stimulation and packaged into exosomes. This exosomal miR-21 was transferred to macrophages, leading to M2 polarization in vitro and in vivo. The therapeutic efficacy of ßMSC-derived exosomes was partially lost upon miR-21 inhibition by its specific inhibitors. More specifically, we demonstrated ßMSCs-derived exosomes inhibited the effects of PDCD4, the target gene of miR-21, on macrophage polarization and sepsis. In conclusion, exosomal miR-21 emerged as a key mediator of IL-1ß pretreatment induced immunomodulatory properties of MSCs. The study indicated a novel basis for therapeutic application of MSCs in sepsis.


Assuntos
Polaridade Celular , Exossomos/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Sepse/genética , Sepse/patologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Sequência de Bases , Células HEK293 , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Fenótipo , Proteínas de Ligação a RNA/metabolismo
16.
Ann Hematol ; 100(1): 105-116, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33089365

RESUMO

Mesenchymal stromal cells (MSCs) represent an essential component of the bone marrow (BM) niche and display disease-specific alterations in several myeloid malignancies. The aim of this work was to study possible MSC abnormalities in Philadelphia-negative myeloproliferative neoplasms (MPNs) in relationship to the degree of BM fibrosis. MSCs were isolated from BM of 6 healthy donors (HD) and of 23 MPN patients, classified in 3 groups according to the diagnosis and the grade of BM fibrosis: polycythemia vera and essential thrombocythemia (PV/ET), low fibrosis myelofibrosis (LF-MF), and high fibrosis MF (HF-MF). MSC cultures were established from 21 of 23 MPN patients. MPN-derived MSCs did not exhibit any functional impairment in their adipogenic/osteogenic/chondrogenic differentiation potential and displayed a phenotype similar to HD-derived MSCs but with a decreased expression of CD146. All MPN-MSC lines were negative for the patient-specific hematopoietic clone mutations (JAK2, MPL, CALR). MSCs derived from HF-MF patients displayed a reduced clonogenic potential and a lower growth kinetic compared to MSCs from HD, LF-MF, and PV/ET patients. mRNA levels of hematopoiesis regulatory molecules were unaffected in MSCs from HF-MF compared to HD. Finally, in vitro ActivinA secretion by MSCs was increased in HF-MF compared to LF-MF patients, in association with a lower hemoglobin value. Increased ActivinA immunolabeling on stromal cells and erythroid precursors was also observed in HF-MF BM biopsies. In conclusion, higher grade of BM fibrosis is associated with functional impairment of MSCs and the increased secretion of ActivinA may represent a suitable target for anemia treatment in MF patients.


Assuntos
Ativinas/metabolismo , Medula Óssea/metabolismo , Células-Tronco Mesenquimais/metabolismo , Transtornos Mieloproliferativos/metabolismo , Mielofibrose Primária/metabolismo , Adulto , Idoso , Medula Óssea/patologia , Diferenciação Celular/fisiologia , Células Cultivadas , Estudos de Coortes , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/patologia , Policitemia Vera/metabolismo , Policitemia Vera/patologia , Mielofibrose Primária/patologia , Trombocitemia Essencial/metabolismo , Trombocitemia Essencial/patologia
17.
Curr Diabetes Rev ; 17(1): 2-10, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32303173

RESUMO

BACKGROUND: Diabetic neuropathies (DN) are the most common complications in diabetic patients, affecting about 70% of them. Patients with DN may lose sensation in certain areas of the body, facilitating the onset of foot ulcers, as well as chronic pain. This is due to the progressive degeneration of nerve fibers, demyelination, and axonopathy. Recent studies about stem cell therapies for the treatment of DN show promising potential for tissue regeneration. Results with mesenchymal stem cells derived from various organs/tissues demonstrate great therapeutic potential considering their easy obtainment, as well as their immunomodulatory and pro-regenerative effects. However, problems such as cell transplant rejection, tumor formation, transplantation safety, and effectiveness still need to be solved. Developmental biology lacks detailed insights into some aspects of cell mechanisms, like the genetic components of cell growth or differentiation. These gaps can limit a rapid advance in stem cell therapy research and put it in the future a little bit farther from the expectations that have emerged in recent media. CONCLUSION: In the present review, we attempt to discuss the potential of most studied types of stem cells, their application for the treatment of experimental diabetic neuropathies and associated clinical manifestations including future perspectives around these themes.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Úlcera do Pé , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Neuropatias Diabéticas/terapia , Humanos , Transplante de Células-Tronco
18.
Life Sci ; 265: 118762, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189825

RESUMO

AIMS: This study is to investigate the role of adenovirus type 36 (Ad36) in inducing differentiation of human adipose-derived stem cells (hADSCs) into brown adipocytes. MAIN METHODS: The hADSCs were induced to differentiate into adipocytes by a cocktail method and Ad36, respectively. They were collected on the 2nd, 4th, 6th, and 8th day, respectively. LncRNA ROR was silenced by siRNA. RT-qPCR and Western-blot were used to detect the mRNA and protein levels. Transmission electron microscopy was used to observe the mitochondria. KEY FINDINGS: The mRNA and protein expression levels of LncRNA ROR, Cidea, Dio2, Fgf21, Ucp1, Prdm16, Cox5b, Atp5o, Atp6, and Nd2 in the Ad36 induction group were significantly higher than those in the cocktail induction group. The expression levels of Leptin mRNA and protein in the Ad36 induction group were significantly lower than those in the cocktail induction group. After siRNA knockdown of LncRNA ROR, mRNA and protein expression levels of Cidea, Dio2, Fgf21, Ucp1, Prdm16, Cox5b, Atp5o, Atp6 and Nd2 were significantly lower than the control group during the induction of hADSC differentiation into adipocytes by Ad36. Additionally, mitochondria in the Ad36 induction group was increased compared to that in the cocktail induction group. SIGNIFICANCE: Ad36 may promote the differentiation of hADSCs into brown adipocytes by up-regulating LncRNA ROR.


Assuntos
Adenoviridae/metabolismo , Infecções por Adenovirus Humanos/metabolismo , Adipócitos Marrons/virologia , Células-Tronco Mesenquimais/metabolismo , RNA Longo não Codificante/metabolismo , Adipócitos Marrons/metabolismo , Adipócitos Marrons/fisiologia , Adipócitos Marrons/ultraestrutura , Western Blotting , Diferenciação Celular , Regulação da Expressão Gênica , Inativação Gênica , Humanos , Microscopia Eletrônica de Transmissão , Mitocôndrias/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
19.
Life Sci ; 265: 118755, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189826

RESUMO

AIMS: The present study was designed to investigate whether the antinociceptive effect of bone marrow-derived mesenchymal stem/stromal cells (MSC) during oxaliplatin (OXL)-induced sensory neuropathy is related to antioxidant properties. MAIN METHODS: Male mice C57BL/6 were submitted to repeated intravenous administration of OXL (1 mg/kg, 9 administrations). After the establishment of sensory neuropathy, mice were treated with a single intravenous administration of MSC (1 × 106), vehicle or gabapentin. Paw mechanical and thermal nociceptive thresholds were evaluated through von Frey filaments and cold plate test, respectively. Motor performance was evaluated in the rota-rod test. Gene expression profile, cytokine levels, and oxidative stress markers in the spinal cord were evaluated by real-time PCR, ELISA and biochemical assays, respectively. KEY FINDINGS: OXL-treated mice presented behavioral signs of sensory neuropathy, such as mechanical allodynia and thermal hyperalgesia, which were completely reverted by a single administration of MSC. Repeated oral treatment with gabapentin (70 mg/kg) induced only transient antinociception. The IL-1ß and TNF-α spinal levels did not differ between mice with or without sensory neuropathy. MSC increased the levels of anti-inflammatory cytokines, IL-10 and TGF-ß, in the spinal cord of neuropathic mice, in addition to increasing the gene expression of antioxidant factors SOD and Nrf-2. Additionally, nitrite and MDA spinal levels were reduced by the MSC treatment. SIGNIFICANCE: MSC induce reversion of sensory neuropathy induced by OXL possibly by activation of anti-inflammatory and antioxidant pathways, leading to reestablishment of redox homeostasis in the spinal cord.


Assuntos
Transplante de Células-Tronco Mesenquimais , Oxaliplatina/toxicidade , Oxirredução , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Células Receptoras Sensoriais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Animais , Interleucina-1beta/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Nociceptividade , Oxirredução/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/terapia , Reação em Cadeia da Polimerase em Tempo Real , Teste de Desempenho do Rota-Rod , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/fisiologia , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Genes (Basel) ; 12(1)2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374593

RESUMO

The placenta is a temporary organ that is discarded after birth and is one of the most promising sources of various cells and tissues for use in regenerative medicine and tissue engineering, both in experimental and clinical settings. The placenta has unique, intrinsic features because it plays many roles during gestation: it is formed by cells from two individuals (mother and fetus), contributes to the development and growth of an allogeneic fetus, and has two independent and interacting circulatory systems. Different stem and progenitor cell types can be isolated from the different perinatal tissues making them particularly interesting candidates for use in cell therapy and regenerative medicine. The primary source of perinatal stem cells is cord blood. Cord blood has been a well-known source of hematopoietic stem/progenitor cells since 1974. Biobanked cord blood has been used to treat different hematological and immunological disorders for over 30 years. Other perinatal tissues that are routinely discarded as medical waste contain non-hematopoietic cells with potential therapeutic value. Indeed, in advanced perinatal cell therapy trials, mesenchymal stromal cells are the most commonly used. Here, we review one by one the different perinatal tissues and the different perinatal stem cells isolated with their phenotypical characteristics and the preclinical uses of these cells in numerous pathologies. An overview of clinical applications of perinatal derived cells is also described with special emphasis on the clinical trials being carried out to treat COVID19 pneumonia. Furthermore, we describe the use of new technologies in the field of perinatal stem cells and the future directions and challenges of this fascinating and rapidly progressing field of perinatal cells and regenerative medicine.


Assuntos
/terapia , Placenta/citologia , Transplante de Células-Tronco/tendências , Células-Tronco/citologia , Líquido Amniótico/citologia , Ensaios Clínicos como Assunto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/tendências , Síndrome da Liberação de Citocina/terapia , Portadores de Fármacos , Membranas Extraembrionárias/citologia , Feminino , Previsões , Células-Tronco Hematopoéticas/citologia , Humanos , Pulmão/patologia , Ativação de Macrófagos , Células-Tronco Mesenquimais/citologia , Nanopartículas , Gravidez , Preservação Biológica , Medicina Regenerativa/métodos , Transplante de Células-Tronco/métodos , Células-Tronco/imunologia
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