Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells

Yang, Guoqiang; Fan, Xuehui; Liu, Yingchun; Jie, Pingping; Mazhar, Maryam; Liu, Yong; Dechsupa, Nathupakorn; Wang, Li

doi:10.1007/s12015-023-10539-9

Cited by 23 publications

(13 citation statements)

References 191 publications

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“…Numerous studies have reported on the success of the MSC therapeutic effect in inflammatory regulation [ 52 ] as well as the amelioration of neuropathology in HD [ 53 , 54 , 55 ]. We applied bone marrow-derived mouse MSCs for the treatment of R6/2 mice via intravenous administration, which has demonstrated to be the best delivery route of MSCs for improving liver function [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…Quantification of mRNA levels showed that the expression level of the Adgre1 gene (encoding protein F4/80) was slightly increased in R6/2-PBS mice vs. WT-PBS mice ( p = 0.0591), while the reduction in R6/2-MSC mice vs. R6/2-PBS mice was highly significant ( p < 0.0001) ( Figure 4 A,B). Furthermore, we analyzed mRNA levels of Cd206 , Cd68 and Cd163 , markers of the M2-type (anti-inflammation) macrophage, where MSCs promote polarization [ 52 ] and in turn increase the population. In all these markers, we did not find any differences in either the R6/2-PBS mice vs. WT-PBS comparisons or between the two R6/2 treatment groups ( Figure 4 C).…”

Section: Resultsmentioning

confidence: 99%

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Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

Yu-Taeger,

El-Ayoubi,

et al. 2024

Cells

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Huntington’s disease (HD), a congenital neurodegenerative disorder, extends its pathological damages beyond the nervous system. The systematic manifestation of HD has been extensively described in numerous studies, including dysfunction in peripheral organs and peripheral inflammation. Gut dysbiosis and the gut–liver–brain axis have garnered greater emphasis in neurodegenerative research, and increased plasma levels of pro-inflammatory cytokines have been identified in HD patients and various in vivo models, correlating with disease progression. In the present study, we investigated hepatic pathological markers in the liver of R6/2 mice which convey exon 1 of the human mutant huntingtin gene. Furthermore, we evaluated the impact of intravenously administered Mesenchymal Stromal Cells (MSCs) on the liver enzymes, changes in hepatic inflammatory markers, as well as brain pathology and behavioral deficits in R6/2 mice. Our results revealed altered enzyme expression and increased levels of inflammatory mediators in the liver of R6/2 mice, which were significantly attenuated in the MSC-treated R6/2 mice. Remarkably, neuronal pathology and altered motor activities in the MSC-treated R6/2 mice were significantly ameliorated, despite the absence of MSCs in the postmortem brain. Our data highlight the importance of hepatic pathological changes in HD, providing a potential therapeutic approach. Moreover, the data open new perspectives for the search in blood biomarkers correlating with liver pathology in HD.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

Yu-Taeger,

El-Ayoubi,

et al. 2024

Cells

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“…Five decades ago, MSCs were first recognized for their pluripotent potential, and recent findings suggest their regenerative and modulatory properties [ 296 ]. MSCs are the source of a myriad of active molecules [ 297 ]. However, concerns about the safety of cell-based therapies still challenge the applicability of MSCs for use in humans [ 298 ].…”

Section: Pharmacology Of Extracellular Vesiclesmentioning

confidence: 99%

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

Al-Jipouri,

Eritja,

Bozic

2023

IJMS

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Extracellular vesicles (EVs) are nanoparticles released from various cell types that have emerged as powerful new therapeutic option for a variety of diseases. EVs are involved in the transmission of biological signals between cells and in the regulation of a variety of biological processes, highlighting them as potential novel targets/platforms for therapeutics intervention and/or delivery. Therefore, it is necessary to investigate new aspects of EVs’ biogenesis, biodistribution, metabolism, and excretion as well as safety/compatibility of both unmodified and engineered EVs upon administration in different pharmaceutical dosage forms and delivery systems. In this review, we summarize the current knowledge of essential physiological and pathological roles of EVs in different organs and organ systems. We provide an overview regarding application of EVs as therapeutic targets, therapeutics, and drug delivery platforms. We also explore various approaches implemented over the years to improve the dosage of specific EV products for different administration routes.

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“…Several studies have investigated MSCs' immunology and their potential to evade and/or influence the immune system of the host [54]. This is in relation to both immunosuppression and/or immunoprivilege.…”

Section: Msc Immunomodulation and Advanced Medicinal Therapymentioning

confidence: 99%

Mesenchymal Stem Cell in Pancreatic Islet Transplantation

Barachini,

Biso,

Kolachalam

et al. 2023

Biomedicines

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Pancreatic islet transplantation is a therapeutic option for achieving physiologic regulation of plasma glucose in Type 1 diabetic patients. At the same time, mesenchymal stem cells (MSCs) have demonstrated their potential in controlling graft rejection, the most fearsome complication in organ/tissue transplantation. MSCs can interact with innate and adaptive immune system cells either through direct cell-cell contact or through their secretome including exosomes. In this review, we discuss current findings regarding the graft microenvironment of pancreatic islet recipient patients and the crucial role of MSCs operation as cell managers able to control the immune system to prevent rejection and promote endogenous repair. We also discuss how challenging stressors, such as oxidative stress and impaired vasculogenesis, may jeopardize graft outcomes. In order to face these adverse conditions, we consider either hypoxia-exposure preconditioning of MSCs or human stem cells with angiogenic potential in organoids to overcome islets’ lack of vasculature. Along with the shepherding of carbon nanotubes-loaded MSCs to the transplantation site by a magnetic field, these studies look forward to exploiting MSCs stemness and their immunomodulatory properties in pancreatic islet transplantation.

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Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells

Cited by 23 publications

References 191 publications

Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

Mesenchymal Stem Cell in Pancreatic Islet Transplantation

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