Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts

2021 ◽  
Author(s):  
Lei Zhang ◽  
Qinghai Wang ◽  
Hang Su ◽  
Jiaxiang Cheng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Diabetic Osteoporosis

scholarly journals Heat Shock Preconditioning Mesenchymal Stem Cells Attenuate Acute Lung Injury via Reducing NLRP3 Inflammasome Activation in Macrophages

2021 ◽  
Author(s):  
Haijin Lv ◽  
Xiaofeng Yuan ◽  
Jiebin Zhang ◽  
Tongyu Lu ◽  
Jia Yao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Pathological Changes ◽  
Nlrp3 Inflammasome Activation

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.

scholarly journals The Activation of NLRP3 Inflammasome Potentiates the Immunomodulatory Abilities of Mesenchymal Stem Cells in Murine Colitis Model

2020 ◽  
Author(s):  
Ji-Su Ahn ◽  
Yoojin Seo ◽  
Su-Jeong Oh ◽  
Ji Won Yang ◽  
Ye Young Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nlrp3 Inflammasome ◽  
Adult Stem Cells ◽  
In Vivo Studies ◽  
Human Umbilical Cord Blood ◽  
Inflammasome Activation ◽  
Human Umbilical Cord ◽  
Nlrp3 Inflammasome Activation

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.

scholarly journals Heat shock preconditioning mesenchymal stem cells attenuate acute lung injury via reducing NLRP3 inflammasome activation in macrophages

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haijin Lv ◽  
Xiaofeng Yuan ◽  
Jiebin Zhang ◽  
Tongyu Lu ◽  
Jia Yao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Pathological Changes ◽  
Nlrp3 Inflammasome Activation

Abstract Objectives Acute lung injury (ALI) remains a common cause of morbidity and mortality worldwide, and to date, there is no effective treatment for ALI. Previous studies have revealed that topical administration of mesenchymal stem cells (MSCs) can attenuate the pathological changes in experimental acute lung injury. Heat shock (HS) pretreatment has been identified as a method to enhance the survival and function of cells. The present study aimed to assess whether HS-pretreated MSCs could enhance immunomodulation and recovery from ALI. Materials and methods HS pretreatment was performed at 42 °C for 1 h, and changes in biological characteristics and secretion functions were detected. In an in vivo mouse model of ALI, we intranasally administered pretreated umbilical cord-derived MSCs (UC-MSCs), confirmed their therapeutic effects, and detected the phenotypes of the macrophages in bronchoalveolar lavage fluid (BALF). To elucidate the underlying mechanisms, we cocultured pretreated UC-MSCs with macrophages in vitro, and the expression levels of inflammasome-related proteins in the macrophages were assessed. Results The data showed that UC-MSCs did not exhibit significant changes in viability or biological characteristics after HS pretreatment. The administration of HS-pretreated UC-MSCs to the ALI model improved the pathological changes and lung damage-related indexes, reduced the proinflammatory cytokine levels, and modulated the M1/M2 macrophage balance. Mechanistically, both the in vivo and in vitro studies demonstrated that HS pretreatment enhanced the protein level of HSP70 in UC-MSCs, which negatively modulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in alveolar macrophages. These effects were partially reversed by knocking down HSP70 expression. Conclusion HS pretreatment can enhance the beneficial effects of UC-MSCs in inhibiting NLRP3 inflammasome activation in macrophages during ALI. The mechanism may be related to the upregulated expression of HSP70. Graphical abstract

scholarly journals Mesenchymal stem cell transplantation inhibited high salt-induced activation of the NLRP3 inflammasome in the renal medulla in Dahl S rats

2016 ◽  
Vol 310 (7) ◽  
pp. F621-F627 ◽  
Author(s):  
Qing Zhu ◽  
Xiao-Xue Li ◽  
Weili Wang ◽  
Junping Hu ◽  
Pin-Lan Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nlrp3 Inflammasome ◽  
Renal Medulla ◽  
High Salt ◽  
Inflammasome Activation ◽  
Mesenchymal Stem Cell Transplantation ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory ◽  
Inflammatory Action

Inflammasomes activate caspase-1 to produce interleukin (IL)-1β. Activation of the NLRP3 inflammasome is involved in various renal pathological conditions. It remains unknown whether the NLRP3 inflammasome activation participates in the abnormal renal response to high-salt (HS) diet in Dahl salt-sensitive (S) rats. In addition, our lab recently showed that transplantation of mesenchymal stem cells (MSCs) attenuated HS-induced inflammation in the renal medulla in Dahl S rat. However, it is unclear whether the anti-inflammatory action of MSCs is associated with inhibition of the NLRP3 inflammasome. The present study determined the response of the NLRP3 inflammasome to HS intake and the effect of MSC transplantation on the NLRP3 inflammasome in the renal medulla in Dahl S rats. Immunostaining showed that the inflammasome components NLRP3, ASC, and caspase-1 were mainly present in distal tubules and collecting ducts. Interestingly, the renal medullary levels of these inflammasome components were remarkably increased after a HS diet in Dahl S rats, while remaining unchanged in normal rats. This HS-induced activation of the NLRP3 inflammasome was significantly blocked by MSC transplantation into the renal medulla in Dahl S rats. Furthermore, infusion of a caspase-1 inhibitor into the renal medulla significantly attenuated HS-induced hypertension in Dahl S rats. These data suggest that HS-induced activation of the NLRP3 inflammasome may contribute to renal medullary dysfunction in Dahl S rats and that inhibition of inflammasome activation may be one of the mechanisms for the anti-inflammatory and anti-hypertensive effects of stem cells in the renal medulla in Dahl S rats.

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