Efficacy of Mesenchymal Stem Cells Therapy in Parasitic Infections: Are Anti-parasitic Drugs Combined with MSCs More Effective?

Kian, Mehdi; Mirzavand, Somayeh; Sharifzadeh, Sedigheh; Kalantari, Tahereh; Ashrafmansouri, Marzieh; Nasri, Fatemeh

doi:10.1007/s11686-022-00620-7

Cited by 5 publications

(4 citation statements)

References 74 publications

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“…Likewise, exosomes produced from various cells among nanocargo carrier candidate structures, which have superior properties in terms of size and structure, can also carry active substances with antileishmanial activity. It has also been observed that combination treatments of cells and chemotherapeutic agents have more successful results in terms of antileishmanial effect compared to stem cell alone or chemical-based treatment options alone [112]. Immunotherapy, which is an emerging trend, has added a different perspective to parasitic diseases such as leishmaniasis as a different and personalized medicine.…”

Section: Discussionmentioning

confidence: 99%

Modern Aspects of Leishmaniasis: Basis of Development New Approaches against Infection

Pinar Zorba Yildiz,

Yildirim Koken,

Yavuz

et al. 2024

Current Topics in Zoonoses

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In this review, the basic principles of developing new approaches to leishmaniasis have been stated contrary to the available literature on Leishmania. In general, the morphology of parasites, life cycle, clinical forms, correspondence to epidemiology, and distribution according to species in the world were described. It has been expressed in various aspects of the interaction between host and parasite cell receptors. This plays an extremely important role in vaccine and drug development against leishmaniasis. Immunologically, natural immunocytes emphasize the importance of macrophages and dendritic cells in the Leishmania parasites’ immunopathology. This review will also discourse on the possibilities and necessity for the generation of new treatment technologies for leishmaniasis.

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Section: Discussionmentioning

confidence: 99%

Modern Aspects of Leishmaniasis: Basis of Development New Approaches against Infection

Pinar Zorba Yildiz,

Yildirim Koken,

Yavuz

et al. 2024

Current Topics in Zoonoses

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“…In clinical practice, bone hydatid disease manifests when hydatid lesions infiltrate the bones, predominantly affecting the spine, pelvis, and femur, thereby significantly impairing patient health and functionality ( Monge-Maillo et al, 2017 ). MSCs, known for their application in orthopedics and cardiovascular diseases, have shown potential therapeutic value through their immunomodulatory effects in parasitic infections, aiding in the efficacy of anthelmintic drugs via multiple pathways ( Kian et al, 2022 ). Given that bone tissue harbors a rich supply of MSCs alongside diverse immune cells, previous studies have highlighted the close interaction between MSCs and immune cells ( Fernández-Francos et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of hydatid antigens on mesenchymal stem cells: gene expression alterations and functional consequences

Wang,

Mijiti,

et al. 2024

Front. Microbiol.

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BackgroundCystic echinococcosis, caused by the larval stage of Echinococcus granulosus, remains a global health challenge. Mesenchymal stem cells (MSCs) are renowned for their regenerative and immunomodulatory properties. Given the parasite’s mode of establishment, we postulate that MSCs likely play a pivotal role in the interaction between the parasite and the host. This study aims to explore the response of MSCs to antigens derived from Echinococcus granulosus, the etiological agent of hydatid disease, with the hypothesis that exposure to these antigens may alter MSC function and impact the host’s immune response to the parasite.MethodsMSCs were isolated from mouse bone marrow and co-cultured with ESPs, HCF, or pLL antigens. We conducted high-throughput sequencing to examine changes in the MSCs’ mRNA expression profile. Additionally, cell cycle, migration, and secretory functions were assessed using various assays, including CCK8, flow cytometry, real-time PCR, Western blot, and ELISA.ResultsOur analysis revealed that hydatid antigens significantly modulate the mRNA expression of genes related to cytokine and chemokine activity, impacting MSC proliferation, migration, and cytokine secretion. Specifically, there was a downregulation of chemokines (MCP-1, CXCL1) and pro-inflammatory cytokines (IL-6, NOS2/NO), alongside an upregulation of anti-inflammatory mediators (COX2/PGE2). Furthermore, all antigens reduced MSC migration, and significant alterations in cellular metabolism-related pathways were observed.ConclusionHydatid disease antigens induce a distinct immunomodulatory response in MSCs, characterized by a shift towards an anti-inflammatory phenotype and reduced cell migration. These changes may contribute to the parasite’s ability to evade host defenses and persist within the host, highlighting the complex interplay between MSCs and hydatid disease antigens. This study provides valuable insights into the pathophysiology of hydatid disease and may inform the development of novel therapeutic strategies.

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“…Chemokine expression plays a crucial role in parasite immunity by recruiting multiple immune cells and is one of the main immunomodulatory mechanisms of MSCs ( Yao et al, 2021 ; Zhang et al, 2023 ). Furthermore, in vivo experiments have revealed that transplantation of MSCs can improve the prognosis of hydatid disease by mitigating tissue damage and modulating the immune response, underscoring the significance of MSCs in the parasite–host interaction ( Kian et al, 2022 ). Osteogenic differentiation is an important pathway involved in maintaining physiological bone homeostasis in bone marrow MSCs.…”

Section: Introductionmentioning

confidence: 99%

Exploration of altered miRNA expression and function in MSC-derived extracellular vesicles in response to hydatid antigen stimulation

Wang,

Mijiti,

Jia

et al. 2024

Front. Microbiol.

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BackgroundHydatid disease is caused by Echinococcus parasites and can affect various tissues and organs in the body. The disease is characterized by the presence of hydatid cysts, which contain specific antigens that interact with the host’s immune system. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can regulate immunity through the secretion of extracellular vesicles (EVs) containing microRNAs (miRNAs).MethodsIn this study, hydatid antigens were isolated from sheep livers and mice peritoneal cavities. MSCs derived from mouse bone marrow were treated with different hydatid antigens, and EVs were isolated and characterized from the conditioned medium of MSCs. Small RNA library construction, miRNA target prediction, and differential expression analysis were conducted to identify differentially expressed miRNAs. Functional enrichment and network construction were performed to explore the biological functions of the target genes. Real-time PCR and Western blotting were used for miRNA and gene expression verification, while ELISA assays quantified TNF, IL-1, IL-6, IL-4, and IL-10 levels in cell supernatants.ResultsThe study successfully isolated hydatid antigens and characterized MSC-derived EVs, demonstrating the impact of antigen concentration on MSC viability. Key differentially expressed miRNAs, such as miR-146a and miR-9-5p, were identified, with functional analyses revealing significant pathways like Endocytosis and MAPK signaling associated with these miRNAs’ target genes. The miRNA-HUB gene regulatory network identified crucial miRNAs and HUB genes, such as Traf1 and Tnf, indicating roles in immune modulation and osteogenic differentiation. Protein–protein interaction (PPI) network analysis highlighted central HUB genes like Akt1 and Bcl2. ALP activity assays confirmed the influence of antigens on osteogenic differentiation, with reduced ALP activity observed. Expression analysis validated altered miRNA and chemokine expression post-antigen stimulation, with ELISA analysis showing a significant reduction in CXCL1 expression in response to antigen exposure.ConclusionThis study provides insights into the role of MSC-derived EVs in regulating parasite immunity. The findings suggest that hydatid antigens can modulate the expression of miRNAs in MSC-derived EVs, leading to changes in chemokine expression and osteogenic capacity. These findings contribute to a better understanding of the immunomodulatory mechanisms involved in hydatid disease and provide potential therapeutic targets for the development of new treatment strategies.

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Efficacy of Mesenchymal Stem Cells Therapy in Parasitic Infections: Are Anti-parasitic Drugs Combined with MSCs More Effective?

Cited by 5 publications

References 74 publications

Modern Aspects of Leishmaniasis: Basis of Development New Approaches against Infection

Modern Aspects of Leishmaniasis: Basis of Development New Approaches against Infection

Immunomodulatory effects of hydatid antigens on mesenchymal stem cells: gene expression alterations and functional consequences

Exploration of altered miRNA expression and function in MSC-derived extracellular vesicles in response to hydatid antigen stimulation

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