Pathogenic or Therapeutic Extracellular Vesicles in Rheumatic Diseases: Role of Mesenchymal Stem Cell-Derived Vesicles

Cosenza, Stella; Ruiz, Maxime; Maumus, Marie; Jørgensen, Christian; Noël, Danièle

doi:10.3390/ijms18040889

Cited by 81 publications

(66 citation statements)

References 93 publications

(101 reference statements)

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“…Yet, microvesicles but not exosomes derived from pathfinder cells, another cell type used in cell‐based therapies isolated from the pancreas, were shown to stimulate functional recovery of the pancreas in STZ induced T1DM mice . On the other hand, ameliorative effect of treatment with exosomes derived from MSCs in different autoimmune experimental models including osteoarthritis, systemic lupus erythematosus, rheumatoid arthritis in concordance with the results of the current study may be indicative of the importance of different sources of exosomes and even the source of the MSCs, and the importance of dominant microenvironment …”

Section: Discussionsupporting

confidence: 84%

“…48 On the other hand, ameliorative effect of treatment with exosomes derived from MSCs in different autoimmune experimental models including osteoarthritis, systemic lupus erythematosus, rheumatoid arthritis in concordance with the results of the current study may be indicative of the importance of different sources of exosomes and even the source of the MSCs, and the importance of dominant microenvironment. 49,50…”

Section: Discussionmentioning

confidence: 99%

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Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes

Nojehdehi

Soudi

Hesampour

et al. 2018

J of Cellular Biochemistry

207

142

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Exosomes derived from adipose tissue-derived mesenchymal stem cells (AD-MSCs) have immunomodulatory effects of T-cell inflammatory response and reduction of clinical symptoms on streptozotocin-induced of the type-1 diabetes mellitus (T1DM). Beside control group and untreated T1DM mice, a group of T1DM mice was treated with intraperitoneal injections of characterized exosomes derived from autologous AD-MSCs. Body weight and blood glucose levels were measured during the procedure. Histopathology and immunohistochemistry were used for evaluation of pancreatic islets using hemotoxylin and eosin (H&E) staining and anti-insulin antibody. Isolated splenic mononuclear cells (MNCs) were subjected to splenocytes proliferation assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, immunophenotyping of regulatory T cells and cytokines. A significant increase in the levels of interleukin-4 (IL-4), IL-10, and transforming growth factor-β, and a decrease in the levels of IL-17 and interferon-γ in concordance with the significant increase in the Treg cell ratio in splenic MNCs (P < 0.05) was shown in T1DM mice treated with AD-MSC's exosomes as compared to T1DM untreated mice. This amelioration of autoimmune reaction after treatment of T1DM mice with the AD-MSC exosomes was confirmed with a significant increase in islets using H&E staining and Immunohistochemistry analyses. As expected, body weight, blood glucose levels in a survival of T1DM mice treated with AD-MSC's exosomes were maintained stable in comparison to untreated T1DM mice. It can be concluded that AD-MSC's exosomes exert ameliorative effects on autoimmune T1DM through increasing regulatory T-cell population and their products without a change in the proliferation index of lymphocytes, which makes them more effective and practical candidates.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes

Nojehdehi

Soudi

Hesampour

et al. 2018

J of Cellular Biochemistry

207

142

View full text Add to dashboard Cite

show abstract

“…They contain mRNAs, microRNAs, proteins, and DNA fragments, which are shuttled from donor cells to recipient cells [14]. Many types of cells, such as mesenchymal cells, immune cells, and cancer cells release exosomes [27]. Cancer-derived exosomes contribute to the constituents associated with the tumor environment.…”

Section: Discussionmentioning

confidence: 99%

Mifepristone Inhibits the Migration of Cervical Cancer Cells by Inhibiting Exocrine Secretion

Sang¹,

Wang²,

Zhao³

2018

Pharmacology

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Cervical cancer (CC) is one of the most common gynecological malignancies, and metastasis limits the use of surgical resection. Metapristone (MIF) was reported to suppress the proliferation and migration of several cancer cells. Exosomes play a variety of roles in cellular biological processes. The relation of exosomes and CC is less studied. Cell viability, apoptosis assay and migration assay was conducted in HeLa cells treated by MIF by CCK-8 kit, staining by Annexin V-fluorescein isothiocyanate and propidium iodide, and wound test respectively. ISG15 expression level was examined in MIF-treated HeLa cells by Western blot. The migration of HeLa cells treated by MIF/GW4869 was measured by wound test. MIF suppressed the growth and migration, as well as induced apoptosis of CC cells. MIF inhibited the exocrine secretion of CC cells by upregulating ISG15, while treating CC cells by ISG15 stimulus, IFN, inhibited the secretion of exosomes. The inhibition of exocrine secretion by GW4869 enhanced the migration inhibition of MIF on CC cells. This study demonstrates that MIF suppresses the CC cell migration by inhibiting exocrine secretion through upregulating ISG1.

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“…EVs from both IFN-γ and TNF-α/IFN-γ preconditioned MSCs have previously been observed with larger size distributions tending towards the microvesicle size range (22,49). The biogenesis of microvesicles differs from that of exosomes, and their immunomodulatory potency has been shown to be less than that of exosomes (50).…”

Section: Discussionmentioning

confidence: 99%

Priming of MSCs with inflammation-relevant signals affects extracellular vesicle biogenesis, surface markers, and modulation of T cell subsets

Andrews¹,

Maughon²,

Marklein³

et al. 2020

Preprint

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Although considerable evidence exists supporting the use of mesenchymal stromal cells (MSCs) for treating immune diseases, successful clinical translation has been challenging and has led researchers to investigate cell-free alternatives. MSC-derived extracellular vesicles (MSC-EVs) have been shown to mediate a significant portion of the observed therapeutic effect, including immunosuppression. MSCs have been shown to respond to different aspects of the injury microenvironment such as inflammatory cytokines and hypoxia, although acidosis has not been investigated and different conditions have not been assessed in terms of their effects on MSC-EV function. This study investigated the effects of acidosis, hypoxia, and inflammatory cytokine priming on MSCs and MSC-EVs.We cultured MSCs in the presence of acidosis, hypoxia, or inflammatory cytokines (Interferon-gamma and Tumor Necrosis Factor-alpha) and compared the characteristics of their EVs as well as their uptake by and suppression of different T cell subsets. MSCs showed a greater effect on suppressing activated CD4 + and CD8 + T cells than MSC-EVs.However, MSC-EVs from MSCs primed with acidosis increased CD4 + and CD8 + regulatory T cell frequency in vitro. This functional response was reflected by MSC-EV uptake. MSC-EVs from acidosis-primed MSCs were taken up by CD4 + and CD8 + regulatory T cells at a significantly higher level than MSC-EVs from control, hypoxic, and inflammatory cytokine groups. These data suggest that a simple low-cost alteration in MSC culture conditions, acidosis, can generate extracelluar vesicles that have a desirable influence on anti inflammatory T cell subtypes.

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Pathogenic or Therapeutic Extracellular Vesicles in Rheumatic Diseases: Role of Mesenchymal Stem Cell-Derived Vesicles

Cited by 81 publications

References 93 publications

Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes

Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes

Mifepristone Inhibits the Migration of Cervical Cancer Cells by Inhibiting Exocrine Secretion

Priming of MSCs with inflammation-relevant signals affects extracellular vesicle biogenesis, surface markers, and modulation of T cell subsets

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