scholarly journals Exosomes Derived From Mouse Adipose-derived Mesenchymal Stem Cells Alleviate BAC-induced Mouse Dry Eye Model Via Inhibiting NLRP3 Inflammasome

2021 ◽  
Author(s):  
Guifang Wang ◽  
Honghui Li ◽  
Hongmei Long ◽  
Xileyuan Gong ◽  
Shufang Hu ◽  
...  
BMB Reports ◽  
2020 ◽  
Vol 53 (6) ◽  
pp. 329-334
Author(s):  
Ji-Su Ahn ◽  
Yoojin Seo ◽  
Su-Jeong Oh ◽  
Ji Won Yang ◽  
Ye Young Shin ◽  
...  

2021 ◽  
Author(s):  
Haijin Lv ◽  
Xiaofeng Yuan ◽  
Jiebin Zhang ◽  
Tongyu Lu ◽  
Jia Yao ◽  
...  

Abstract Objectives: Acute lung injury (ALI) remains one of the common causes of morbidity and mortality worldwide, so far, without any effective therapeutic approach. Previous researches have revealed that topical administration of umbilical cord-derived mesenchymal stem cells (UC-MSCs) can attenuate pathological changes in experimental acute lung injury. Heat shock (HS) pretreatment has been identified as a method to enhance survival and function of cells. The present study aimed to assess whether HS-pretreated mesenchymal stem cells (MSCs) could strengthen the immunomodulation and recovery from ALI. Materials and Methods: HS pretreatment was defined 42℃ for 1h, the changes of biological characteristics and the secreted functions were detected. In the mouse model of ALI, we intranasally dripped the pretreated UC-MSCs in vivo, confirmed their therapeutic effects and detected the phenotypes of macrophages in bronchoalveolar lavage fluid (BALF). To elucidate their mechanisms, we co-cultured the pretreated UC-MSCs with macrophages in vitro, and the expression levels of inflammasome-related proteins in macrophages were assessed. Finally, Apoptozole was used for further determine the role of HSP70 in HS-pretreated UC-MSCs-based therapy. Results: The data showed that UC-MSCs did not represented significant changes in viability and biological characterizations after received HS pretreatment. Administration of HS-pretreated UC-MSCs into the ALI model, improved pathological changes and lung damage-related indexes, reduced of the levels of pro-inflammatory cytokines and modulated the balance of M1/M2. Mechanistically, both in vivo and in vitro studies demonstrated that HS pretreatment enhanced the protein level of HSP70 in UC-MSCs and subsequently upregulated the synthesis and secretion of PGE2, which negatively modulated the NLRP3 inflammasome activation of alveolar macrophages. And these effects was partially reversed by Apoptozole. Conclusion: HS pretreatment can strengthen the beneficial effects of UC-MSCs on inhibiting NLRP3 inflammasome activation of macrophages in ALI. The mechanism may be contributed to the upregulated expression of HSP70 to further induce PGE2 synthesis and secretion.


2021 ◽  
Vol 4 (1) ◽  
pp. 42-53
Author(s):  
Chen Mei ◽  
Li Jie ◽  
Peng Jun ◽  
Huang Yu ◽  
Ouyang Weijie ◽  
...  

2021 ◽  
Vol 91 (4) ◽  
pp. 349-358
Author(s):  
Basak Boztok Ozgermen ◽  
◽  
Pinar Can ◽  
İrem Sancak ◽  
Eylul Akpinar ◽  
...  

Keratoconjunctivitis Sicca (KCS), also known as “dry eye syndrome”, is a common ocular disease in dogs, caused by inflammation of the lacrimal gland, resulting in decreased tear production. Efforts are being made to develop alternative therapies in order to prevent lifelong use of drugs for patients with KCS. Mesenchymal stem cells (MSCs) are known to be effective in the treatment of many immune-mediated diseases in human and animal models due to their immunoregulatory properties. The aim of this study was to transplant limbal mesenchymal stem cells (LMSCs) to the ocular surface on contact lenses and to evaluate the therapeutic effects of the LMSCs by clinical examination findings. The animals were randomly divided into study and control groups. The LMSC group (n = 10) received LMSCs (at least 2×106 cells) cultured on contact lenses. The conventional treatment group (n = 10) received artificial tears, topical 0.05% Cs A, and antibiotic eye drops, 3 times a day for 4 weeks. The Schirmer test, tear break-up time, impression cytology, Rose Bengal staining, and tear osmolarity were measured in all patients. The findings of the pre-treatment, two weeks and four weeks after the treatment, were evaluated statistically. In both groups, significant improvement was present compared to the pre-treatment findings. However, there was no significant difference between the groups. KCS treatment using LMSCs produced on contact lenses is promising, with its ease of application, non-immunogenic properties and single dose administration.


2020 ◽  
Author(s):  
Ji-Su Ahn ◽  
Yoojin Seo ◽  
Su-Jeong Oh ◽  
Ji Won Yang ◽  
Ye Young Shin ◽  
...  

Abstract Background Inflammasomes are cytosolic, multiprotein complexes which act at the frontline of the immune responses by recognizing pathogen or danger-associated molecular patterns of pathogens or abnormal host molecules. Mesenchymal stem cells (MSCs) have been reported to possess multipotency to differentiate into various cell types and immunoregulatory effects which make them a promising treatment for regenerative medicine and immune-related diseases, respectively. However, little is known about the expression and role of the inflammasome in adult stem cells. In this study, we investigated the expression and functional regulation of NLRP3 inflammasome in human umbilical cord blood-derived MSCs (hUCB-MSCs). Methods The expression of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome was detected in hUCB-MSCs. Cell proliferation, death and differentiation were analyzed after NLRP3 inflammasome activation. To investigate the changes in immunoregulatory functions of hUCB-MSCs, naïve or NLRP3 inflammasome-stimulated cells were infused into chemically induced colitic mice and symptoms were monitored. Results NLRP3 inflammasome activation suppressed the differentiation of hUCB-MSCs into osteoblasts, which was restored when the expression of adaptor proteins for inflammasome assembly was inhibited. Moreover, the suppressive effects of MSCs on T cell responses and the macrophage activation were augmented in response to NLRP3 activation. In vivo studies using colitic mice revealed that the protective abilities of hUCB-MSCs increased after NLRP3 stimulation. Conclusions Our findings suggest that the NLRP3 inflammasome components are expressed in hUCB-MSCs and its activation can regulate the differentiation capability and the immunomodulatory effects of hUCB-MSCs.


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