scholarly journals In vitro and in vivo efficacy of Albendazole Chitosan Microspheres with Intensity-modulated Radiation Therapy in the treatment of spinal echinococcosis

2021 ◽  
Author(s):  
Sibo Wang ◽  
Shan Wang ◽  
Weishan Wang ◽  
Yi Dai ◽  
Zhongpeng Qiu ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Intensity Modulated Radiation Therapy ◽  
Confocal Imaging ◽  
Ultrastructural Changes ◽  
Therapeutic Effects ◽  
Inhibition Rate ◽  
Chitosan Microspheres ◽  
Intensity Modulated

Currently, there is a lack of clinically safe and effective treatment for spinal cystic echinococcosis (CE). Recent studies have shown that albendazole chitosan microspheres (ABZ-CS-MPS) and irradiation have certain anti-abdominal echinococcosis ability, so this study aims to compare the in vitro and in vivo therapeutic effects of ABZ-CS-MPs, Intensity-modulated radiation therapy (IMRT) and the combination therapy on spinal echinococcosis. Firstly, protoscolices were processed by different treatments to evaluate their respective anti-echinococcosis effect by monitoring the viability change of protoscoleces. Then, the apoptotic status of protoscoleces was evaluated by detecting the changes of mitochondrial membrane potential, the expression of apoptosis proteins and the ultrastructural alterations of protoscoleces. After that, we constructed a gerbil model of spinal CE and further applied B-ultrasound and magnetic resonance imaging technology to assess the size of hydatid in vivo. Finally, the cysts were obtained and weighed to compare the inhibition rate in different groups. The combined therapy increased protoscoleces mortality to over 90% after 18 days, which showed the highest scolicidal effect. Moreover, confocal imaging, expression of apoptotic proteins and ultrastructural changes of protoscoleces showed the highest apoptotic rate in this group. In vivo, the combination treatment also exhibited the highest cyst inhibition rate (61.4%). In conclusion, our results showed that ABZ-CS-MPs combined with IMRT could be a new treatment option for spinal CE. We also provided a method to evaluate the growth and metastasis of hydatid in animals with B-ultrasound and MRI imaging technologies.

Abstract 15483: Regenerative Effects of Exosomes Secreted by Cardiospheres in a Rat Model of Chronic Myocardial Infarction Are Mimicked by Exosome-primed Fibroblasts

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Eleni Tseliou ◽  
Joseph Fouad ◽  
Geoffrey de Couto ◽  
Ryan Middleton ◽  
Liu Weixin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Tube Formation ◽  
Dermal Fibroblasts ◽  
Confocal Imaging ◽  
Therapeutic Effects ◽  
Chronic Myocardial Infarction ◽  
Self Assembling ◽  
Wistar Kyoto

Background: Multicellular self-assembling cardiospheres (CSps) exert regenerative and anti-fibrotic effects via paracrine mechanisms. CSp-derived cells are known to secrete exosomes which mediate most or all of the beneficial therapeutic effects. Objective: We evaluated the regenerative capacity of CSp-secreted exosomes in a model of chronic myocardial infarction (MI). We also determined whether CSp-exosomes could convert the phenotype of therapeutically-inert cells. Methods: Exosomes were isolated from CSp-conditioned media by adding a precipitation solution followed by centrifugation. One month post-MI, Wistar Kyoto rats (n=46) with permanent LAD ligation were injected intramyocardially with: a) human dermal fibroblasts (DFs), b) CSp exosomes, c) DFs primed with CSp-exosomes, d) CSps only or e) vehicle. Functional and histological analyses were performed 4 weeks after therapy. Mechanisms were also probed in vitro . Results: In vivo, CSp-exosomes and CSps equally increased ejection fraction (EF= 45±1% [CSp-exo], 44±2% [CSps], 33±1% [placebo] and 35±2% [DFs]) and reduced scar mass (48±8mg [CSp-exo], 45±4mg [CSps], 96±12mg [placebo] and 90±6mg [DFS]; both p<0.01 by one way ANOVA). DFs that had been incubated with CSp-exosomes for 24 hours in culture conferred enhanced benefits compared to unprimed DFs (EF= 41±1% [primed-DFs]; p=0.05 vs unprimed DFs; scar mass= 49±5mg [primed-DFs]; p<0.01 vs unprimed DFs). Confocal imaging revealed internalization of fluorescently-labeled CSp-exosomes in exosome-primed DFs. In vitro , exosome-primed DFs increased tube formation by HUVECs and inhibited cardiomyocyte apoptosis. Immunohistochemistry showed increased vessel density in all groups compared to vehicle or unprimed DFs. Conclusions: Administration of CSp-exosomes recapitulates the regenerative potential and functional benefits of CSps themselves. The surprising ability of CSp-exosomes to confer therapeutic efficacy on inert DFs may represent an unanticipated amplification mechanism for exosome-mediated benefits.

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