Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders

Shomali, Navid; Gharibi, Tohid; Vahedi, Ghasem; Mohammed, Rebar N.; Mohammadi, Hamed; Salimifard, Sevda; Marofi, Faroogh

doi:10.1002/jcp.29324

Cited by 29 publications

(26 citation statements)

References 108 publications

(182 reference statements)

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“…However, either mesenchymal stromal/stem cells or IL-37 showed limited roles to relieve intestinal IRI [25,26,39]…”

Section: Discussionmentioning

confidence: 99%

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IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

Kong

et al. 2020

Preprint

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Background: Ischemia reperfusion injury (IRI) is the major cause of intestinal damage in clinic. Although either mesenchymal stromal cells (MSCs) or interleukin 37 (IL-37) showed some beneficial roles to ameliorate IRI, their effects are limited. In this study, the protective effects of IL-37 gene-modified MSCs (IL-37-MSCs) for better prevention of intestinal IRI are investigated.Methods: Intestinal IRI model was established by occluding the superior mesenteric artery for 30min and then reperfusing for 72 hours in rats. Forty adult male SD rats were randomly divided into sham control, IL-37-MSC-treated, MSC-treated, recombinant IL-37 (rIL-37)-treated and untreated groups. Intestinal damage was assessed by H&E staining. The levels of gut barrier function factors (diamine oxidase and D-Lactate) and inflammation reactivity cytokine IL-1β were assayed by ELISA. The expressions of tissue damage-related NLRP3 inflammasome and relative proteins including clevead caspase-1, IL-1β and IL-18 were detected by western blot. As downstream of IL-1β and IL-18, the mRNA levels of proinflammatory mediators IL-6 and TNF-α were determined by qPCR. Data were analyzed by one-way analysis of variance among groups.Results: IL-37-MSCs were able to migrate to the damaged tissue and significantly inhibit intestinal IRI. As compared with MSCs or rIL-37 monotherapy group, IL-37-MSC treatment not only improved gut barrier function but also decreased local and systemic inflammation reactivity cytokine IL-1β level in IRI rats. In addition, tissue damage-related NLRP3 and relative proteins (cleaved caspase-1, IL-1β and 4 IL-18) were significantly decreased in IRI rats treated with IL-37-MSCs. Furthermore, IL-1β and IL-18 related proinflammatory mediators IL-6 and TNF-α mRNA expressions were markedly decreased following IL-37-MSC treatment.Conclusion: The results suggest that IL-37 gene modification significantly enhance the protective effects of MSCs against intestinal IRI. In addition, NLRP3-related signaling pathways could be associated with IL-37-MSC mediated protection.

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“…However, either mesenchymal stromal/stem cells or IL-37 showed limited roles to relieve intestinal IRI [25,26,39]…”

Section: Discussionmentioning

confidence: 99%

“…Although MSCs and IL-37 could protect organs against IRI, their roles were limited for many reasons [25,26]. Thus, it is necessary to combine them together to enhance their therapeutic effects.…”

Section: Irimentioning

confidence: 99%

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

Kong

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…However, either mesenchymal stromal cells or IL-37 showed limited roles to relieve intestinal IRI [25,26,39]…”

Section: Discussionmentioning

confidence: 99%

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

Dejun¹,

Hu²,

Li³

et al. 2020

Preprint

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Background : Ischemia reperfusion injury (IRI) is the major cause of intestinal damage in clinic. Although either mesenchymal stromal cells (MSCs) or interleukin 37 (IL-37) showed some beneficial roles to ameliorate IRI, their effects are limited. In this study, the protective effects of IL-37 gene-modified MSCs (IL-37-MSCs) for better prevention of intestinal IRI are investigated. Methods: Intestinal IRI model was established by occluding the superior mesenteric artery for 30min and then reperfusing for 72 hours in rats. Forty adult male SD rats were randomly divided into sham control, IL-37-MSC-treated, MSC-treated, recombinant IL-37 (rIL-37)-treated and untreated groups. Intestinal damage was assessed by H&E staining. The levels of gut barrier function factors (diamine oxidase and D-Lactate) and inflammation reactivity cytokine IL-1β were assayed by ELISA. The expressions of tissue damage-related NLRP3 inflammasome and relative proteins including clevead caspase-1, IL-1β and IL-18 were detected by western blot. As downstream of IL-1β and IL-18, the mRNA levels of proinflammatory mediators IL-6 and TNF-α were determined by qPCR. Data were analyzed by one-way analysis of variance among groups. Results : IL-37-MSCs were able to migrate to the damaged tissue and significantly inhibit intestinal IRI. As compared with MSCs or rIL-37 monotherapy group, IL-37-MSC treatment not only improved gut barrier function but also decreased local and systemic inflammation reactivity cytokine IL-1β level in IRI rats. In addition, tissue damage-related NLRP3 and relative proteins (cleaved caspase-1, IL-1β and IL-18) were significantly decreased in IRI rats treated with IL-37-MSCs. Furthermore, IL-1β and IL-18 related proinflammatory mediators IL-6 and TNF-α mRNA expressions were markedly decreased following IL-37-MSC treatment. Conclusion : The results suggest that IL-37 gene modification significantly enhance the protective effects of MSCs against intestinal IRI. In addition, NLRP3-related signaling pathways could be associated with IL-37-MSC mediated protection.

show abstract

“…Although MSCs and IL-37 could protect organs against IRI, their roles are limited for many reasons [25,26]. Thus, it is necessary to combine them together to enhance their individual therapeutic effects.…”

Section: Introductionmentioning

confidence: 99%

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

Kong

et al. 2020

Stem Cells International

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Background. Ischemia reperfusion injury (IRI) is the major cause of intestinal damage in clinic. Although either mesenchymal stromal cells (MSCs) or interleukin 37 (IL-37) shows some beneficial roles to ameliorate IRI, their effects are limited. In this study, the preventative effects of IL-37 gene-modified MSCs (IL-37-MSCs) on intestinal IRI are investigated. Methods. Intestinal IRI model was established by occluding the superior mesenteric artery for 30 minutes and then reperfused for 72 hours in rats. Forty adult male Sprague-Dawley rats were randomly divided into the sham control, IL-37-MSC-treated, MSC-treated, recombinant IL-37- (rIL-37-) treated, and untreated groups. Intestinal damage was assessed by H&E staining. The levels of gut barrier function factors (diamine oxidase and D-Lactate) and inflammation cytokine IL-1β were assayed using ELISA. The synthesis of tissue damage-related NLRP3 inflammasome and downstream cascade reactions including cleaved caspase-1, IL-1β, and IL-18 was detected by western blot. The mRNA levels of proinflammatory mediators IL-6 and TNF-α, which are downstream of IL-1β and IL-18, were determined by qPCR. Data were analyzed by one-way analysis of variance (ANOVA) after the normality test and followed by post hoc analysis with the least significant difference (LSD) test. Results. IL-37-MSCs were able to migrate to the damaged tissue and significantly inhibit intestinal IRI. As compared with MSCs or the rIL-37 monotherapy group, IL-37-MSC treatment both improved gut barrier function and decreased local and systemic inflammation cytokine IL-1β level in IRI rats. In addition, tissue damage-related NLRP3 and downstream targets (cleaved caspase-1, IL-1β, and IL-18) were significantly decreased in IRI rats treated with IL-37-MSCs. Furthermore, IL-1β- and IL-18-related proinflammatory mediator IL-6 and TNF-α mRNA expressions were all significantly decreased in IRI rats treated with IL-37-MSCs. Conclusion. The results suggest that IL-37 gene modification significantly enhances the protective effects of MSCs against intestinal IRI. In addition, NLRP3-related signaling pathways could be associated with IL-37-MSC-mediated protection.

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Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders

Cited by 29 publications

References 108 publications

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

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