scholarly journals Reproducible Large-Scale Isolation of Exosomes from Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Application in Acute Kidney Injury

2020 ◽  
Vol 21 (13) ◽  
pp. 4774 ◽  
Author(s):  
Jun Ho Lee ◽  
Dae Hyun Ha ◽  
Hyeon-kyu Go ◽  
Jinkwon Youn ◽  
Hyun-keun Kim ◽  
...  

Acute kidney injury (AKI) is a fatal medical episode caused by sudden kidney damage or failure, leading to the death of patients within a few hours or days. Previous studies demonstrated that exosomes derived from various mesenchymal stem/stromal cells (MSC-exosomes) have positive effects on renal injuries in multiple experimental animal models of kidney diseases including AKI. However, the mass production of exosomes is a challenge not only in preclinical studies with large animals but also for successful clinical applications. In this respect, tangential flow filtration (TFF) is suitable for good manufacturing practice (GMP)-compliant large-scale production of high-quality exosomes. Until now, no studies have been reported on the use of TFF, but rather ultracentrifugation has been almost exclusively used, to isolate exosomes for AKI therapeutic application in preclinical studies. Here, we demonstrated the reproducible large-scale production of exosomes derived from adipose tissue-derived MSC (ASC-exosomes) using TFF and the lifesaving effect of the ASC-exosomes in a lethal model of cisplatin-induced rat AKI. Our results suggest the possibility of large-scale stable production of ASC-exosomes without loss of function and their successful application in life-threatening diseases.

2020 ◽  
Vol 21 (24) ◽  
pp. 9689
Author(s):  
Angela Casas ◽  
Adrián Mallén ◽  
Arnau Blasco-Lucas ◽  
Fabrizio Sbraga ◽  
Jordi Guiteras ◽  
...  

Cardiovascular mortality increases with decreasing renal function although the cause is yet unknown. Here, we have investigated whether low chronic inflammation in chronic kidney diseases (CKD) could contribute to increased risk for coronary artery diseases (CAD). Thus, a prospective case–control study was conducted in patients with CAD and CKD undergoing coronary artery bypass graft surgery with the aim of detecting differences in cardiovascular outcomes, epicardial adipose tissue volume, and inflammatory marker activity associated with renal dysfunction. Expression of membrane CD14 and CD16, inflammatory cytokines and chemokines, mitogen-activated protein (MAP) kinases and hsa-miR-30a-5p were analyzed in peripheral blood mononuclear cells (PBMCs). Epicardial fat volume and tissue inflammation in perivascular adipose tissue and in the aorta were also studied. In the present study, 151 patients were included, 110 with CAD (51 with CKD) and 41 nonCAD controls (15 with CKD). CKD increased the risk of cardiac surgery–associated acute kidney injury (CSA-AKI) as well as the 30-day mortality after cardiac surgery. Higher counts of CD14++CD16+ monocytes were associated with vascular inflammation, with an increased expression of IL1β, and with CKD in CAD patients. Expression of hsa-miR-30a-5p was correlated with hypertension. We conclude that CKD patients show an increased risk of CSA-AKI and mortality after cardiovascular surgery, associated with the expansion of the CD14++CD16+ subset of proinflammatory monocytes and with IL1β expression. We propose that inflammation associated with CKD may contribute to atherosclerosis (ATH) pathogenesis.


2008 ◽  
pp. 110306231138043
Author(s):  
Francesco D'andrea ◽  
Francesco De Francesco ◽  
Giuseppe A. Ferraro ◽  
Vincenzo Desiderio ◽  
Virginia Tirino ◽  
...  

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 411 ◽  
Author(s):  
Daniela Lisini ◽  
Sara Nava ◽  
Simona Frigerio ◽  
Simona Pogliani ◽  
Guido Maronati ◽  
...  

Mesenchymal stromal cells (MSCs) prepared as advanced therapies medicinal products (ATMPs) have been widely used for the treatment of different diseases. The latest developments concern the possibility to use MSCs as carrier of molecules, including chemotherapeutic drugs. Taking advantage of their intrinsic homing feature, MSCs may improve drugs localization in the disease area. However, for cell therapy applications, a significant number of MSCs loaded with the drug is required. We here investigate the possibility to produce a large amount of Good Manufacturing Practice (GMP)-compliant MSCs loaded with the chemotherapeutic drug Paclitaxel (MSCs-PTX), using a closed bioreactor system. Cells were obtained starting from 13 adipose tissue lipoaspirates. All samples were characterized in terms of number/viability, morphology, growth kinetics, and immunophenotype. The ability of MSCs to internalize PTX as well as the antiproliferative activity of the MSCs-PTX in vitro was also assessed. The results demonstrate that our approach allows a large scale expansion of cells within a week; the MSCs-PTX, despite a different morphology from MSCs, displayed the typical features of MSCs in terms of viability, adhesion capacity, and phenotype. In addition, MSCs showed the ability to internalize PTX and finally to kill cancer cells, inhibiting the proliferation of tumor lines in vitro. In summary our results demonstrate for the first time that it is possible to obtain, in a short time, large amounts of MSCs loaded with PTX to be used in clinical trials for the treatment of patients with oncological diseases.


2013 ◽  
Vol 22 (2) ◽  
pp. 287-297 ◽  
Author(s):  
Takayuki Katsuno ◽  
Takenori Ozaki ◽  
Yosuke Saka ◽  
Kazuhiro Furuhashi ◽  
Hangsoo Kim ◽  
...  

2008 ◽  
Vol 14 (3) ◽  
pp. 233-242 ◽  
Author(s):  
Francesco D'Andrea ◽  
Francesco De Francesco ◽  
Giuseppe A. Ferraro ◽  
Vincenzo Desiderio ◽  
Virginia Tirino ◽  
...  

1993 ◽  
Vol 32 (1) ◽  
pp. 129-131
Author(s):  
Naureen Talha

The literature on female labour in Third World countries has become quite extensive. India, being comparatively more advanced industrially, and in view of its size and population, presents a pictures of multiplicity of problems which face the female labour market. However, the author has also included Mexico in this analytical study. It is interesting to see the characteristics of developing industrialisation in two different societies: the Indian society, which is conservative, and the Mexican society, which is progressive. In the first chapter of the book, the author explains that he is not concerned with the process of industrialisation and female labour employed at different levels of work, but that he is interested in forms of production and women's employment in large-scale production, petty commodity production, marginal small production, and self-employment in the informal sector. It is only by analysis of these forms that the picture of females having a lower status is understood in its social and political setting.


Sign in / Sign up

Export Citation Format

Share Document