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1.
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
2.
Medicine (Baltimore) ; 99(49): e23343, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285713

RESUMO

OBJECTIVE: To evaluate the effects and safety of intra-articular injection of mesenchymal stem cells on patients with knee osteoarthritis by a systematic review and meta-analysis. METHODS: PubMed, EMBASE, and Cochrane Library were retrieved. An assessment of the risk of bias was done through the Cochrane Collaborative Bias Risk Tool, publication bias was assessed by plotting funnel plots and Egger tests. Pain and functional improvements in patients with knee osteoarthritis were determined by changes in VAS scores and WOMAC scores at baseline and follow-up endpoints. For the evaluation of MRI, the WORMS score and changes in cartilage volume were used. In addition, the number of adverse events in the intervention group and the control group were counted to explore the safety. RESULTS: A total of 10 randomized controlled trials involving 335 patients were included. In the pooled analysis, compared with the control groups, the VAS scores of MSC groups decreased significantly (MD,-19.24; 95% CI: -26.31 to -12.18, P < .00001. All of the WOMAC scores also improved significantly: the total scores (SMD, - 0.66; 95% CI: - 1.09 to -0.23, P = .003), pain scores (SMD, - 0.46; 95% CI: - 0.75 to -0.17, P = .002), stiffness scores (SMD, -0.32; 95% CI: -0.64 to 0.00 P = 0.05), and functional scores (SMD, -0.36; 95% CI: -0.69 to -0.04, P = .03). Two studies with non-double-blind designs were the main source of heterogeneity. In terms of cartilage repair, there was no significant difference in the WORMS score, but there was a significant increase in cartilage volume in the MSC group (SMD, 0.69; 95% CI: 0.25 to 1.13, P = .002). The proportion of patients with adverse events in the MSCs treatment group was significantly higher than that in the control group (OR, 3.20; 95% CI: 1.50 to 6.83, P = .003). CONCLUSIONS: Intra-articular injection of mesenchymal stem cells is effective and safety to relieve pain and improve motor function of patients with knee osteoarthritis in a short term which is different to conclusions of previous study.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite do Joelho/terapia , Humanos , Injeções Intra-Articulares , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Manejo da Dor/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular , Recuperação de Função Fisiológica
3.
J Transl Med ; 18(1): 451, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256746

RESUMO

BACKGROUND: During the coronavirus disease-2019 (COVID-19) pandemic, Italian hospitals faced the most daunting challenges of their recent history, and only essential therapeutic interventions were feasible. From March to April 2020, the Laboratory of Advanced Cellular Therapies (Vicenza, Italy) received requests to treat a patient with severe COVID-19 and a patient with acute graft-versus-host disease with umbilical cord-derived mesenchymal stromal cells (UC-MSCs). Access to clinics was restricted due to the risk of contagion. Transport of UC-MSCs in liquid nitrogen was unmanageable, leaving shipment in dry ice as the only option. METHODS: We assessed effects of the transition from liquid nitrogen to dry ice on cell viability; apoptosis; phenotype; proliferation; immunomodulation; and clonogenesis; and validated dry ice-based transport of UC-MSCs to clinics. RESULTS: Our results showed no differences in cell functionality related to the two storage conditions, and demonstrated the preservation of immunomodulatory and clonogenic potentials in dry ice. UC-MSCs were successfully delivered to points-of-care, enabling favourable clinical outcomes. CONCLUSIONS: This experience underscores the flexibility of a public cell factory in its adaptation of the logistics of an advanced therapy medicinal product during a public health crisis. Alternative supply chains should be evaluated for other cell products to guarantee delivery during catastrophes.


Assuntos
/terapia , Assistência à Saúde/organização & administração , Gelo-Seco , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Sistemas Automatizados de Assistência Junto ao Leito/organização & administração , Transportes , Doença Aguda , /patologia , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Assistência à Saúde/normas , Equipamentos e Provisões Hospitalares/normas , Equipamentos e Provisões Hospitalares/provisão & distribução , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Itália/epidemiologia , Administração de Materiais no Hospital/organização & administração , Administração de Materiais no Hospital/normas , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/normas , Células-Tronco Mesenquimais/fisiologia , Organização e Administração/normas , Pandemias , Fenótipo , Sistemas Automatizados de Assistência Junto ao Leito/normas , Índice de Gravidade de Doença , Transportes/métodos , Transportes/normas
4.
PLoS One ; 15(11): e0235239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33166292

RESUMO

Although rotator cuff disease is a common cause of shoulder pain, there is still no treatment method that could halt or reveres its development and progression. The purpose of this study was to investigate the efficacy of umbilical cord-derived mesenchymal stem cells (UC MSCs) on the regeneration of a full-thickness rotator cuff defect (FTD) in a rat model. We injected either UC MSCs or saline to the FTD and investigated macroscopic, histological and biomechanical results and cell trafficking. Treatment with UC MSCs improved macroscopic appearance in terms of tendon thickness at two weeks, and inflammation, defect size, swelling/redness and connection surrounding tissue and slidability at four weeks compared to the saline group. Histologically, UC MSCs induced the tendon matrix formation recovering collagen organization, nuclear aspect ratio and orientation angle of fibroblast as well as suppressing cartilage-related glycosaminoglycan compared to saline group at four weeks. The UC MSCs group also improved ultimate failure load by 25.0% and 19.0% and ultimate stress by 27.3% and 26.8% at two and four weeks compared to saline group. UC MSCs labeled with PKH26 exhibited 5.3% survival at four weeks compared to three hours after injection. This study demonstrated that UC MSCs regenerated the FTD with tendon tissue similar properties to the normal tendon in terms of macroscopic, histological and biomechanical characteristics in a rat model.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Regeneração , Lesões do Manguito Rotador/terapia , Traumatismos dos Tendões/terapia , Animais , Fenômenos Biomecânicos , Masculino , Ratos , Ratos Sprague-Dawley , Lesões do Manguito Rotador/patologia , Traumatismos dos Tendões/patologia
5.
Int J Nanomedicine ; 15: 9181-9195, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33239875

RESUMO

Purpose: Stem cell therapy for ischemic stroke has shown success in experimental settings, but its translation into clinical practice is challenging. The choroid plexus (CP) plays a regulatory role in neural regeneration. Mesenchymal stem cells (MSCs) promote neurogenesis in the ventricular-subventricular zone. However, it is unclear whether MSCs interact with the CP in brain tissue repair. Methods: Rat (r)MSCs were labeled with iron oxide nanoparticles (IONs) and transduced with red fluorescent protein, and then injected into the brain of rats with ischemic stroke and monitored over time by magnetic resonance imaging. The functional recovery of rats was determined by the corner test score, Modified Neurological Severity score, and stroke volume. MSCs and CP were also co-cultured for 14 days, and the medium was analyzed with a cytokine array. Results: In vivo imaging and histologic analysis revealed that ION-labeled MSCs were mainly located at the injection site and migrated to the infarct area and to the CP. Functional recovery was greater in rats treated with MSCs as compared to those that received mock treatment. Bidirectional enhancement of proliferation in MSCs and CP was observed in the co-culture; moreover, MSCs migrated to the CP. Cytokine analysis revealed elevated levels of proliferation- and adhesion-related cytokines and chemokines in the culture medium. Wikipathway predictions indicated that insulin-like growth factor 1/Akt signaling (WP3675), chemokine signaling pathway (WP2292), and spinal cord injury (WP2432) are involved in the increased proliferation and migration of MSCs co-cultured with the CP. Conclusion: Crosstalk with the CP enhances MSC proliferation and migration in a transwell assay. Moreover, MRI reveals MSC migration towards the CP in an ischemic stroke model. The secreted factors resulting from this interaction have therapeutic potential for promoting functional recovery in the brain after ischemic stroke.


Assuntos
Plexo Corióideo/citologia , /química , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/química , Animais , Proliferação de Células , Quimiocinas/metabolismo , Plexo Corióideo/metabolismo , Técnicas de Cocultura , Citocinas/metabolismo , Modelos Animais de Doenças , Células HEK293 , Humanos , /patologia , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Imagem por Ressonância Magnética , Masculino , Células-Tronco Mesenquimais/citologia , Regeneração Nervosa , Ratos , Traumatismo por Reperfusão
6.
Mol Biol Rep ; 47(12): 9939-9949, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33185828

RESUMO

The outbreak of a novel coronavirus namely SARS-CoV-2, which first emerged from Wuhan, China, has wreaked havoc not only in China but the whole world that now has been engulfed in its wrath. In a short lapse of time, this virus was successful in spreading at a blistering pace throughout the globe, hence raising the flag of pandemic status. The mounting number of deaths with each elapsing day has summoned researchers from all around the world to play their part in driving this SARS-CoV-2 pandemic to an end. As of now, multiple research teams are immersed in either scrutinizing various antiviral drugs for their efficacy or developing different types of vaccines that will be capable of providing long-term immunity against this deadly virus. The mini-review sheds light on the possible approaches that can be undertaken to curb the COVID-19 spread. Possible strategies comprise viral vector-based, nucleic acid-based, protein-based, inactivated and weakened virus vaccines; COVID-19 vaccine being developed by deploying Hyleukin-7 technology; plant-based chimeric protein and subunit vaccines; humanized nano-bodies and human antibodies; intravenous immunoglobulin (IVIG) infusion therapy; inhibitors for ACE-2, Angiotensin 1 receptor (AT1R), complement system, viral proteins, host cell protease and endocytosis; shield immunity; IL-6R, NKG2A and hACE2-SARS-CoV-2-RBD interaction blocking monoclonal antibodies; SARS-CoV RdRp-based drugs, traditional Chinese medicine, repositioned and anti-viral drugs. These vaccines and drugs are currently being screened in the clinical trials as several of them have manifested positive results, hence increasing the probability of becoming one of the potential treatments for this disease.


Assuntos
Antivirais/farmacologia , /tratamento farmacológico , /prevenção & controle , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Anticorpos Monoclonais/farmacologia , Ensaios Clínicos como Assunto , Reposicionamento de Medicamentos , Humanos , Vírus da Bronquite Infecciosa/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , RNA Mensageiro/imunologia , Proteínas Recombinantes/genética , Anticorpos de Domínio Único/farmacologia , Vacinas Atenuadas/farmacologia , Vacinas de Subunidades/farmacologia , Vacinas Sintéticas/farmacologia
7.
Stem Cell Res Ther ; 11(1): 437, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059757

RESUMO

The COVID-19 pandemic has negatively impacted the global public health and the international economy; therefore, there is an urgent need for an effective therapy to treat COVID-19 patients. Mesenchymal stem cells (MSCs) have been proposed as an emerging therapeutic option for the SARS-CoV-2 infection. Recently, numerous clinical trials have been registered to examine the safety and efficacy of different types of MSCs and their exosomes for treating COVID-19 patients, with less published data on the mechanism of action. Although there is no approved effective therapy for COVID-19 as of yet, MSC therapies showed an improvement in the treatment of some COVID-19 patients. MSC's therapeutic effect is displayed in their ability to reduce the cytokine storm, enhance alveolar fluid clearance, and promote epithelial and endothelial recovery; however, the safest and most effective route of MSC delivery remains unclear. The use of poorly characterized MSC products remains one of the most significant drawbacks of MSC-based therapy, which could theoretically promote the risk for thromboembolism. Optimizing the clinical-grade production of MSCs and establishing a consensus on registered clinical trials based on cell-product characterization and mode of delivery would aid in laying the foundation for a safe and effective therapy in COVID-19. In this review, we shed light on the mechanistic view of MSC therapeutic role based on preclinical and clinical studies on acute lung injury and ARDS; therefore, offering a unique correlation and applicability in COVID-19 patients. We further highlight the challenges and opportunities in the use of MSC-based therapy.


Assuntos
Lesão Pulmonar Aguda/terapia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/terapia , Exossomos/transplante , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Lesão Pulmonar Aguda/virologia , Betacoronavirus , Terapia Baseada em Transplante de Células e Tecidos/métodos , Humanos , Células-Tronco Mesenquimais/metabolismo , Pandemias
8.
Life Sci ; 263: 118588, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049279

RESUMO

The severe acute respiratory syndrome-novel coronavirus mediated COVID-19 has been recently declared a pandemic by the World Health Organization. The primary target of the SARS-CoV-2 virus is the human lungs governed by the ACE-2 receptor of epithelial type II cells/endothelial cells, which promote modulation of the immune response of host cells through generating cytokine storm, inflammation, severe pneumonia symptoms, and secondary complications such as acute respiratory distress syndrome. Although numerous antiviral and anti-parasitic drugs are under clinical trials to combat this pandemic, to date, neither a specific treatment nor any successful vaccine has been established, urging researchers to identify any potential candidate for combating the disease. Mesenchymal stem cells own self-renewal, differentiation, homing, immunomodulation and remains unaffected by the coronavirus on the virtue of the absence of ACE-2 receptors, indicating that MSC's could be used an ameliorative approach for COVID-19. MSCs have shown to combat the disease via various pathways such as repairing the lung epithelial and endothelial cells, reducing hyperimmune response, maintaining the renin-angiotensin system. Although MSCs-based treatment approaches for COVID-19 is still under consideration with limited data, many human clinical trials of MSC's has been initiated to explore their potential for COVID 19 treatment. The current review summarizes and emphasizes on how MSC's modulate the immune response, can repair the lungs from the impact of the virus, and various aspects of MSC's as a remedial source for COVID-19, to provide better insight for biomedical researchers and for those who are fascinated by stem cells as a therapeutic approach.


Assuntos
/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Animais , Células Endoteliais/imunologia , Células Epiteliais/imunologia , Humanos , Imunomodulação/fisiologia , Pulmão/imunologia , Pulmão/virologia , Células-Tronco Mesenquimais/imunologia , Regeneração/fisiologia , /isolamento & purificação
9.
Cell Prolif ; 53(12): e12939, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33098357

RESUMO

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 mainly causes damage to the lung, as well as other organs and systems such as the hearts, the immune system and so on. Although the pathogenesis of COVID-19 has been fully elucidated, there is no specific therapy for the disease at present, and most treatments are limited to supportive care. Stem cell therapy may be a potential treatment for refractory and unmanageable pulmonary illnesses, which has shown some promising results in preclinical studies. In this review, we systematically summarize the pathogenic progression and potential mechanisms underlying stem cell therapy in COVID-19, and registered COVID-19 clinical trials. Of all the stem cell therapies touted for COVID-19 treatment, mesenchymal stem cells (MSCs) or MSC-like derivatives have been the most promising in preclinical studies and clinical trials so far. MSCs have been suggested to ameliorate the cytokine release syndrome (CRS) and protect alveolar epithelial cells by secreting many kinds of factors, demonstrating safety and possible efficacy in COVID-19 patients with acute respiratory distress syndrome (ARDS). However, considering the consistency and uniformity of stem cell quality cannot be quantified nor guaranteed at this point, more work remains to be done in the future.


Assuntos
/tratamento farmacológico , Transplante de Células-Tronco Mesenquimais , /patogenicidade , /virologia , Humanos , Pulmão/virologia , Transplante de Células-Tronco Mesenquimais/métodos
10.
Cell Prolif ; 53(12): e12938, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33124125

RESUMO

OBJECTIVE: Premature ovarian insufficiency (POI) is a refractory disease that seriously affects female fertility. Growing body of evidence has indicated mesenchymal stem cells (MSCs) as promising resources in regenerative medicine. In this study, we treated POI patients with umbilical cord-derived MSCs (UCMSCs) and then investigated the restoration of ovarian function and clinical outcomes through follow-ups. MATERIALS AND METHODS: Sixty-one patients diagnosed with POI participated in this study. UCMSCs were isolated and cultured according to GMP standards, and then transplanted to the patients' ovary by orthotopic injection under the guidance of vaginal ultrasound. We monitored side effects, vital signs and changes in clinical and collected haematological and imaging parameters during the follow-ups. RESULTS: All patients showed normal clinical behaviour without serious side effects or complications relevant to the treatment. Transplantation of UCMSCs rescued the ovarian function of POI patients, as indicated by increased follicular development and improved egg collection. POI patients who experienced shorter amenorrhoea durations (<1 year) seemed to obtain mature follicles more easily after stem cell therapy, and patients with better ovarian conditions (pre-operative antral follicles) were more likely to derive the better outcomes by UCMSC injection. Four successful clinical deliveries were obtained from POI patients after UCMSC transplantation, and all of these babies are developed normally. CONCLUSIONS: The clinical trial result sugggests a possible therapy for POI by UCMSC transplantation.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Insuficiência Ovariana Primária/terapia , Cordão Umbilical/citologia , Apoptose/fisiologia , Feminino , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Ovário/citologia , Pacientes
11.
J Vis Exp ; (163)2020 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-33016944

RESUMO

One of the major issues facing current cardiac stem cell therapies for preventing postinfarct heart failure is the low retention and survival rates of transplanted cells within the injured myocardium, limiting their therapeutic efficacy. Recently, the use of scaffolding biomaterials has gained attention for improving and maximizing stem cell therapy. The objective of this protocol is to introduce a simple and straightforward technique to transplant bone marrow-derived mesenchymal stem cells (MSCs) using injectable hydroxyphenyl propionic acid (GH) hydrogels; the hydrogels are favorable as a cell delivery platform for cardiac tissue engineering applications due to their ability to be cross-linked in situ and high biocompatibility. We present a simple method to fabricate MSC-loading GH hydrogels (MSC/hydrogels) and evaluate their survival and proliferation in three-dimensional (3D) in vitro culture. In addition, we demonstrate a technique for intramyocardial transplantation of MSC/hydrogels in mice, describing a surgical procedure to induce myocardial infarction (MI) via left anterior descending (LAD) coronary artery ligation and subsequent MSC/hydrogels transplantation.


Assuntos
Hidrogéis , Transplante de Células-Tronco Mesenquimais/métodos , Infarto do Miocárdio/terapia , Animais , Materiais Biocompatíveis , Modelos Animais de Doenças , Injeções , Camundongos , Engenharia Tecidual
12.
Life Sci ; 263: 118600, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33068598

RESUMO

MATERIALS AND METHODS: In this study, 10 male Shall sheep were used in two groups and bone marrow samples were collected and BM-MSCs isolated. Then experimental model of ARDS was induced by intrapulmonary injection of LPS to dose of 400 µg/kg. Twenty-four hours after LPS injection, 5 × 107 cells of BM-MSCs were autologous transferred in the group of treatment and 1 ml PBS was infused in the group of control as intrapulmonary. Then, the symptoms of clinical, complete blood count, analysis of arterial blood gases and the concentrations of IL6,IL10,TNF-α,total protein, Ig M and albumin BAL were determined before and at times of 3,6,12,24,48,72, and 168 after transplantation/infusion. KEY FINDINGS: The results of the investigations 24 h post-LPS injection(time 0) indicated the occurrence of acute inflammation which confirmed ARDS model. These changes included increase in RR, HR and RT, decrease in PO2 and SatO2 and increase in PCO2, WBC, neutrophils, macrophages, total protein,IL6,IL10, TNF-α,Ig M and albumin. But the stem/stromal cells transplantation reduced the severity of clinical signs induced by LPS, caused significant increase in PO2, SatO2 and IL-10 and significant decrease in PCO2, the total protein, TNF-α,IL-6, Ig M, albumin, WBCs, neutrophils and macrophages at different times of sampling both in compared with before transplantation(time 0) and in compared with the group of control. While in the control group, inflammation continued until the end of the study. SIGNIFICANCE: These results showed that BM-MSCs are able to reduce inflammation and have an important role in reconstruction of the damaged lung.


Assuntos
Inflamação/terapia , Macrófagos/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , /prevenção & controle , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/patologia , Lipopolissacarídeos , Masculino , Neutrófilos/metabolismo , Ovinos
13.
Cytotherapy ; 22(11): 602-605, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32933835

RESUMO

The serious consequences of the global coronavirus disease 2019 (COVID-19) pandemic have prompted a rapid global response to develop effective therapies that can lessen disease severity in infected patients. Cell-based approaches, primarily using mesenchymal stromal cells (MSCs), have demonstrated a strong safety profile and possible efficacy in patients with acute respiratory distress syndrome (ARDS), but whether these therapies are effective for treating respiratory virus-induced ARDS is unknown. According to the World Health Organization International Clinical Trials Registry Platform and the National Institutes of Health ClinicalTrials.gov databases, 27 clinical investigations of MSC-based cell therapy approaches have begun in China since the onset of the COVID-19 outbreak, with a growing number of academic and industry trials elsewhere as well. Several recent published reports have suggested potential efficacy; however, the available data presented are either anecdotal or from incomplete, poorly controlled investigations. Therefore, although there may be a potential role for MSCs and other cell-based therapies in treatment of COVID-19, these need to be investigated in a rationally designed, controlled approach if safety and efficacy are to be demonstrated accurately. The authors urge that the field proceed by finding a balance between swift experimentation and communication of results and scientifically coherent generation and analysis of clinical data.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , /terapia , Betacoronavirus , China , Humanos , Células-Tronco Mesenquimais/citologia , Pandemias
14.
Am J Physiol Lung Cell Mol Physiol ; 319(6): L908-L925, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32901521

RESUMO

Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical bronchoalveolar lavage fluid (BALF) samples, as a surrogate for the in vivo clinical lung environment, on MSC viability, gene expression, secreted cytokines, and mitochondrial function were compared with effects of BALF collected from healthy volunteers. CF BALF samples that cultured positive for Aspergillus sp. (Asp) induced rapid MSC death, usually within several hours of exposure. Further analyses suggested the fungal toxin gliotoxin as a potential mediator contributing to CF BALF-induced MSC death. RNA sequencing analyses of MSCs exposed to either Asp+ or Asp- CF BALF samples identified a number of differentially expressed transcripts, including those involved in interferon signaling, antimicrobial gene expression, and cell death. Toxicity did not correlate with bacterial lung infections. These results suggest that the potential use of MSC-based cell therapies for CF or other lung diseases may not be warranted in the presence of Aspergillus.


Assuntos
Anti-Inflamatórios/uso terapêutico , Fibrose Cística/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Líquido da Lavagem Broncoalveolar/microbiologia , Fibrose Cística/metabolismo , Humanos , Pulmão/metabolismo , Pulmão/microbiologia , Transplante de Células-Tronco Mesenquimais/métodos
15.
Int J Mol Sci ; 21(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899381

RESUMO

Respiratory and pulmonary diseases are among the leading causes of death globally. Despite tremendous advancements, there are no effective pharmacological therapies capable of curing diseases such as COPD (chronic obstructive pulmonary disease), ARDS (acute respiratory distress syndrome), and COVID-19. Novel and innovative therapies such as advanced therapy medicinal products (ATMPs) are still in early development. However, they have exhibited significant potential preclinically and clinically. There are several longitudinal studies published, primarily focusing on the use of cell therapies for respiratory diseases due to their anti-inflammatory and reparative properties, thereby hinting that they have the capability of reducing mortality and improving the quality of life for patients. The primary objective of this paper is to set out a state of the art review on the use of aerosolized MSCs and their potential to treat these incurable diseases. This review will examine selected respiratory and pulmonary diseases, present an overview of the therapeutic potential of cell therapy and finally provide insight into potential routes of administration, with a focus on aerosol-mediated ATMP delivery.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Doença Pulmonar Obstrutiva Crônica/terapia , /terapia , Animais , Humanos , Transplante de Células-Tronco Mesenquimais/instrumentação , Nebulizadores e Vaporizadores , Pandemias
16.
Pain Physician ; 23(4S): S391-S420, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32942796

RESUMO

BACKGROUND: Although only a small percentage of patients with COVID-19 deteriorate to a critical condition, because of the associated high mortality rate and the sheer number of cases, it imposes a tremendous burden on the society and unprecedented strains the health care resources. Albeit lung is the primary organ involved resulting in acute respiratory distress syndrome (ARDS), many patients additionally present with secondary multiorgan failure. Unfortunately, there is no definitive or curative treatment for this condition, and the management has been predominantly confined to supportive care, which necessitates an urgent need for novel therapies. Mesenchymal stem cell (MSC) therapy has a vast array of preclinical data and early, preliminary clinical data that suggests its potential to regenerate and restore the function of damaged tissues and organs. To date, there has been no review of all the clinical trials that have assessed the safety and efficacy of MSC therapy in organ failure commonly seen in seriously complicated COVID-19 patients. OBJECTIVES: To evaluate the effectiveness of MSC therapy in managing multiorgan failure, utilizing currently available literature. STUDY DESIGN: A review of human randomized controlled trials (RCTs) and observational studies assessing the role of MSC therapy in managing multiorgan failure. METHODS: PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1990 through May 2020. Studies that included embryonic stem cells, induced pluripotent stem cells, differentiated MSCs into specific lineage cells, and hematopoietic stem cells were excluded. Trials with intraorgan infiltration of MSC were also excluded. OUTCOME MEASURES: The primary outcome evaluated the improvement in clinical assessment scores and indices of organ function. The secondary outcome assessed the safety of MSC therapy in the clinical trials. RESULTS: Based on search criteria, 12 studies were found for lung, 52 for heart, 23 for liver, 16 for stroke, and 9 for kidney. Among the 6 studies that specifically assessed the effectiveness of MSC therapy in ARDS, 4 showed positive outcomes. Forty-one of the 52 trials that examined ischemic and nonischemic heart failure reported beneficial effects. Twenty of 23 trials for liver failure from different etiologies revealed favorable outcomes. Nine out of the 15 studies evaluating stroke had satisfactory effects. However, only 3 out of the 9 studies for kidney failure showed positive results. Nonexpanded bone marrow mononuclear cells were used in most of the negative studies. The incidence of disease worsening or major complications was extremely rare from MSC therapy. LIMITATIONS: Among the studies evaluated, although there were many RCTs, there were also numerous case series. Additionally, most recruited a small number of patients. CONCLUSIONS: MSC therapy seems to be promising to treat multiorgan failure from COVID-19. More studies are urgently needed to assess both safety and efficacy.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Insuficiência de Múltiplos Órgãos/terapia , Insuficiência de Múltiplos Órgãos/virologia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Betacoronavirus , Humanos , Estudos Observacionais como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Pain Physician ; 23(4S): S421-S432, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32942797

RESUMO

OBJECTIVE: There are as yet no effective strategies to treat the novel COVID-19 and to stem its symptoms, including ARDS. This review examines recent research studies in humans to determine whether mesenchymal stem cells (MSCs) may be used effectively and safely to target potentially deadly lung damage that may follow infection. METHODS: A literature search was conducted to find published manuscripts on the treatment of ARDS and COVID-19 symptoms, disease presentation, and available treatment regimens. Electronic data bases of scientific articles and records of printed documents of JAMA journals were searched to find research publications on MSC treatment of ARDS and COVID-19. Outcome variables included mortality over varying time periods, hospital days, days on ventilator, and biological factors. RESULTS: Two randomized double-blind clinical trials, 2 pilot studies, and 2 case reports described MSC use to treat ARDS with specific focus on COVID-19 and lung symptoms of cytokine storm. The MSCs were well-tolerated across studies. No significant differences in treatment outcome were found in randomized double-blind trials; however, results of 1 pilot study and 1 case report showed that MSCs led to lung symptom resolution and survival in severely ill treatment patients. CONCLUSIONS: There is little published research on disease and survival outcomes among patients suffering severe lung disease associated with ARDS and COVID-19, and studies available are limited by lack of consistency in design and numerous flaws and limitations. Comparisons across studies are difficult. Nevertheless, it is documented that 8 ARDS patients with COVID-19 experienced symptom recovery and survival subsequent to MSC administration. MSCs are potentially life-saving treatment approaches for some patients who exhibit severe lung distress and have not responded to standard treatments. This is an obviously exciting research and treatment option for COVID-19 and other life-threatening diseases.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/complicações , Pneumonia Viral/terapia , /virologia , Betacoronavirus , Feminino , Humanos , Pandemias , Resultado do Tratamento
18.
J Int Med Res ; 48(9): 300060520955063, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32972277

RESUMO

At the end of 2019, novel coronavirus (COVID-19) infection was detected in Wuhan City, Hubei Province, China. The COVID-19 infection characteristics include a long incubation period, strong infectivity, and high fatality rate, and it negatively affects human health and social development. COVID-19 has become a common problem in the global medical and health system. It is essentially an acute self-limiting disease. Patients with severe COVID-19 infection usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death within a short period after onset. There remains a lack of effective drugs for such patients clinically. Mesenchymal stem cells (MSCs) are expected to reduce the risk of complications and death in patients because they have strong anti-inflammatory and immunomodulatory capabilities, which can improve the microenvironment, promote neovascularization, and enhance tissue repair capabilities. China is currently conducting several clinical trials on MSCs for the treatment of COVID-19. Here, we review the research progress related to using stem cells to treat patients with COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Pneumonia Viral/terapia , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/virologia , Prognóstico
19.
J Plast Reconstr Aesthet Surg ; 73(11): 2025-2032, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32919950

RESUMO

BACKGROUND: Autologous lipotransfer (AL) is a popular method despite unpredictable retention rates. Higher retention rates have been reported when co-administering adipose-derived stem cells (ASCs), a process called cell-assisted lipotransfer (CAL). Our hypothesis is that CAL might indeed limit volume gain in most women seeking aesthetic breast augmentation because it doubles the amount of fat required without consistently improving the outcome. METHODS: Electronic databases were searched for articles published between January 2008 and October 2019 in English and German. All original articles evaluating fat viability following autologous breast augmentation in vivo were included. Based on the reported retention rates, potential volume gains were estimated for CAL and AL. RESULTS: A total of 23 studies were selected. The AL retention rate varied from 39% to 76%, whereas CAL increased this rate at best by 24%. The body mass index (BMI) ranged from 18.8 to 23.4 (20.4±1.6) in the study population, whereas the BMI of women in the same age group is 28.7 (±8.4). We calculated that, starting from 200 ml of harvested fat and after two sessions of AL of 100 ml each, the volume retained would be at most 152 ml. In contrast, after one session of CAL of 100 ml, while the remaining 100 ml are used to isolate ASCs, a maximum of 95 ml of fat would remain. CONCLUSION: The volume gain after two sessions of AL is far superior to that after one session of CAL for the same volume of harvested fat. This is an important practical consideration for women with low BMI, as the extra fat required to isolate ASCs is not counterbalanced by an increase in the retention rate. Therefore, two sessions of AL may be preferable to maximize the volume gain.


Assuntos
Mamoplastia/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Gordura Subcutânea/transplante , Adulto , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Avaliação de Processos e Resultados em Cuidados de Saúde , Coleta de Tecidos e Órgãos/métodos
20.
Life Sci ; 262: 118385, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926926

RESUMO

Diabetic nephropathy (DN) is a chronic inflammatory complication of diabetes mellitus, which becomes the most common cause of end-stage renal disease (ESRD). Recently, bone marrow mesenchymal stem cells (BMSCs) are considered as a promising therapy for DN. However, the protective mechanism of BMSCs on DN remains unclear. This study was done to explore the effect of a bone marrow stromal cell (BMSCs) transplant on DN rats and rat glomerular mesangial cells in high-glucose concentration. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin (STZ) 65 mg/kg, then 4 × 106 BMSCs were transplanted in diabetic rats as the treatment group. Six weeks after BMSCs transplantation, blood serum creatinine (Scr) and blood urea nitrogen (BUN) were used to test renal function. Renal pathological examination was observed by HE staining, Masson staining, PAS staining and immunohistochemistry. The results demonstrated that BMSCs could dramatically improve renal function and collagen accumulation by reducing Scr, BUN, collagen I and IV expression and histopathological abnormalities in the diabetic kidneys. Furthermore, BMSCs could significantly attenuate the expression of TLR4/NF-κB and MCP-1 in vitro and in vivo (P < 0.05, vs diabetic groups). This study reported a novel finding that BMSCs play a protective role in inhibition of inflammatory and fibrotic cytokines by down-regulating TLR-4/NF-κB expression under diabetic condition.


Assuntos
Diabetes Mellitus Experimental/terapia , Nefropatias Diabéticas/prevenção & controle , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Nitrogênio da Ureia Sanguínea , Células Cultivadas , Creatinina/sangue , Citocinas/metabolismo , Diabetes Mellitus Experimental/complicações , Feminino , Fibrose , Glucose/metabolismo , Células Mesangiais/metabolismo , NF-kappa B/genética , Ratos , Ratos Sprague-Dawley , Estreptozocina , Receptor 4 Toll-Like/genética
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