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<t>MSC-derived</t> sEV treatment decreases clinical severity scores in murine sepsis (A) Diagram of murine cecal slurry model. Mice were injected with cecal slurry IP, to induce polymicrobial sepsis. At 6 h post-injection, MSC-derived <t>sEVs</t> or sEV-depleted media were administered via tail vein injection. When mice reached a sepsis score of 15 or above or at 24 h post-IP injection, the brain tissue was harvested. (B) MSC-derived sEV treatment ( n = 26) in mice 6 h after the onset of sepsis resulted in improved disease overall severity score as compared with the untreated septic mice ( n = 19) (∗∗∗ p = 0.0005) and lower peak scores (∗∗∗∗ p < 0.0001). (C) MSC-derived sEV treatment improved scores at 24 h in neurological-only parameters (i.e., level of consciousness, activity, response to stimulus) as compared with the untreated septic mice (∗ p = 0.01). Data are represented as mean ± SEM, one-way ANOVA. ANOVA: Analysis of Variance, IP: intraperitoneally, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant.

Msc Derived Sevs, supplied by ZenBio, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Average 90 stars, based on 1 article reviews

msc-derived sevs - by Bioz Stars, 2026-07

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Article Title: Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy

Journal: iScience

doi: 10.1016/j.isci.2024.110573

MSC-derived sEV treatment decreases clinical severity scores in murine sepsis (A) Diagram of murine cecal slurry model. Mice were injected with cecal slurry IP, to induce polymicrobial sepsis. At 6 h post-injection, MSC-derived sEVs or sEV-depleted media were administered via tail vein injection. When mice reached a sepsis score of 15 or above or at 24 h post-IP injection, the brain tissue was harvested. (B) MSC-derived sEV treatment ( n = 26) in mice 6 h after the onset of sepsis resulted in improved disease overall severity score as compared with the untreated septic mice ( n = 19) (∗∗∗ p = 0.0005) and lower peak scores (∗∗∗∗ p < 0.0001). (C) MSC-derived sEV treatment improved scores at 24 h in neurological-only parameters (i.e., level of consciousness, activity, response to stimulus) as compared with the untreated septic mice (∗ p = 0.01). Data are represented as mean ± SEM, one-way ANOVA. ANOVA: Analysis of Variance, IP: intraperitoneally, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant.

Figure Legend Snippet: MSC-derived sEV treatment decreases clinical severity scores in murine sepsis (A) Diagram of murine cecal slurry model. Mice were injected with cecal slurry IP, to induce polymicrobial sepsis. At 6 h post-injection, MSC-derived sEVs or sEV-depleted media were administered via tail vein injection. When mice reached a sepsis score of 15 or above or at 24 h post-IP injection, the brain tissue was harvested. (B) MSC-derived sEV treatment ( n = 26) in mice 6 h after the onset of sepsis resulted in improved disease overall severity score as compared with the untreated septic mice ( n = 19) (∗∗∗ p = 0.0005) and lower peak scores (∗∗∗∗ p < 0.0001). (C) MSC-derived sEV treatment improved scores at 24 h in neurological-only parameters (i.e., level of consciousness, activity, response to stimulus) as compared with the untreated septic mice (∗ p = 0.01). Data are represented as mean ± SEM, one-way ANOVA. ANOVA: Analysis of Variance, IP: intraperitoneally, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant.

Techniques Used: Derivative Assay, Injection, Activity Assay

Sepsis-induced cerebellar injury is reversed by MSC-derived sEVs (A–D) Representative photomicrographs of H&E and TUNEL staining in the mouse cerebellum show significant histopathological alterations during sepsis. Compared to controls, which exhibited intact cellular architecture with clear, rounded nuclei, the septic mouse cerebellum displayed (A) significant histopathological alterations including shrunken PCs, pyknotic nuclei (black arrows), perineuronal vacuole formation (Materials and Methods: Tissue processing and histological assessment) and (B) increased TUNEL labeled cells (white arrows) indicating DNA fragmentation and cell death. Overall, sepsis resulted in (C) increased neuropathological score and (D) TUNEL+ cells (∗∗∗∗ p < 0.0001 and ∗∗∗∗ p < 0.0001) which both improved with MSC-derived sEV treatment (∗ p = 0.0155 and ∗∗ p = 0.0063). Data are represented as mean ± SEM, one-way ANOVA. Scale bar = 10 μm, Control ( n = 7), Sepsis+media ( n = 8), Sepsis+MSC-derived sEVs ( n = 8). ANOVA: Analysis of Variance, DNA: Deoxyribonucleic Acid, H&E: Hematoxylin and Eosin, NS: non-significant, PC: Purkinje cells, TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles.

Figure Legend Snippet: Sepsis-induced cerebellar injury is reversed by MSC-derived sEVs (A–D) Representative photomicrographs of H&E and TUNEL staining in the mouse cerebellum show significant histopathological alterations during sepsis. Compared to controls, which exhibited intact cellular architecture with clear, rounded nuclei, the septic mouse cerebellum displayed (A) significant histopathological alterations including shrunken PCs, pyknotic nuclei (black arrows), perineuronal vacuole formation (Materials and Methods: Tissue processing and histological assessment) and (B) increased TUNEL labeled cells (white arrows) indicating DNA fragmentation and cell death. Overall, sepsis resulted in (C) increased neuropathological score and (D) TUNEL+ cells (∗∗∗∗ p < 0.0001 and ∗∗∗∗ p < 0.0001) which both improved with MSC-derived sEV treatment (∗ p = 0.0155 and ∗∗ p = 0.0063). Data are represented as mean ± SEM, one-way ANOVA. Scale bar = 10 μm, Control ( n = 7), Sepsis+media ( n = 8), Sepsis+MSC-derived sEVs ( n = 8). ANOVA: Analysis of Variance, DNA: Deoxyribonucleic Acid, H&E: Hematoxylin and Eosin, NS: non-significant, PC: Purkinje cells, TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles.

Techniques Used: Derivative Assay, TUNEL Assay, Staining, Labeling, Control, End Labeling

RNA-seq reveals MSC-derived sEV-induced changes in cerebellar transcriptome following sepsis (A and B) Predicted activated (green) and inhibited (gray) causal networks and canonical pathways (determined by directional z-scores) in septic mice treated with MSC-derived sEVs compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. (C) Predicted increases (green) and decreases (gray) in cell and molecular functions (determined by directional z-scores) in septic mice treated with MSC-derived sEVs compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. (D) Predicted activated (green) and inhibited (gray) upstream regulators (determined by directional z-scores) in in septic mice treated with MSC-derived sEVs compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. (E) Heatmap of most significantly predicted upstream regulators when septic mice treated with MSC-derived sEVs are compared to untreated septic mice. Boxes are colorized with z-scores (green = activated, gray = inactivated). Source data are provided as a source data file.

Figure Legend Snippet: RNA-seq reveals MSC-derived sEV-induced changes in cerebellar transcriptome following sepsis (A and B) Predicted activated (green) and inhibited (gray) causal networks and canonical pathways (determined by directional z-scores) in septic mice treated with MSC-derived sEVs compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. (C) Predicted increases (green) and decreases (gray) in cell and molecular functions (determined by directional z-scores) in septic mice treated with MSC-derived sEVs compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. (D) Predicted activated (green) and inhibited (gray) upstream regulators (determined by directional z-scores) in in septic mice treated with MSC-derived sEVs compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. (E) Heatmap of most significantly predicted upstream regulators when septic mice treated with MSC-derived sEVs are compared to untreated septic mice. Boxes are colorized with z-scores (green = activated, gray = inactivated). Source data are provided as a source data file.

Techniques Used: RNA Sequencing Assay, Derivative Assay

MSC-derived sEVs affect cytokine concentration in septic mouse cerebellum TNF-α and IL-17α assessed by immunofluorescence. (A) Representative photomicrograph of TNF-α, PV and IL-17α staining in low (x1.4, left) and high (×60, right) magnification of the area included in the hatched box. TNF-α was expressed and co-localized with the PC and their dendrites. (B and C) TNF-α expression significantly increased in SE compared to controls (5.2 ± 1.1 vs. 1.4 ± 0.2, p = 0.0085), however, treatment with MSC-derived sEVs restored its expression by more than 50% (1.9 ± 0.2, p = 0.03). Notably, TNF-α was not expressed in parvalbumin (PV)+ interneurons (a and c) that surround the PCs. (D) The expression of IL-17α was similar in control and septic mice (5.62E+09 ± 2.7E+08 vs. 7.8E+09 ± 3.7E+08, p = 0.1096), however, treatment with MSC-derived sEVs doubled its expression (1.52E+10 ± 1.3E+09, p =<0.0001). Data are represented as mean ± SEM, one-way ANOVA. Scale bar = 10 μm, Control ( n = 6), Sepsis+media [for TNF-α ( n = 7) and IL-17α ( n = 8)], Sepsis+MSC-derived sEVs [(for TNF-α ( n = 5) and IL-17α ( n = 6)]. MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant, TNFα: tumor necrosis factor alpha, IL-17α: interleukin 17 alpha, ANOVA: Analysis of Variance, PV: parvalbumin.

Figure Legend Snippet: MSC-derived sEVs affect cytokine concentration in septic mouse cerebellum TNF-α and IL-17α assessed by immunofluorescence. (A) Representative photomicrograph of TNF-α, PV and IL-17α staining in low (x1.4, left) and high (×60, right) magnification of the area included in the hatched box. TNF-α was expressed and co-localized with the PC and their dendrites. (B and C) TNF-α expression significantly increased in SE compared to controls (5.2 ± 1.1 vs. 1.4 ± 0.2, p = 0.0085), however, treatment with MSC-derived sEVs restored its expression by more than 50% (1.9 ± 0.2, p = 0.03). Notably, TNF-α was not expressed in parvalbumin (PV)+ interneurons (a and c) that surround the PCs. (D) The expression of IL-17α was similar in control and septic mice (5.62E+09 ± 2.7E+08 vs. 7.8E+09 ± 3.7E+08, p = 0.1096), however, treatment with MSC-derived sEVs doubled its expression (1.52E+10 ± 1.3E+09, p =<0.0001). Data are represented as mean ± SEM, one-way ANOVA. Scale bar = 10 μm, Control ( n = 6), Sepsis+media [for TNF-α ( n = 7) and IL-17α ( n = 8)], Sepsis+MSC-derived sEVs [(for TNF-α ( n = 5) and IL-17α ( n = 6)]. MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant, TNFα: tumor necrosis factor alpha, IL-17α: interleukin 17 alpha, ANOVA: Analysis of Variance, PV: parvalbumin.

Techniques Used: Derivative Assay, Concentration Assay, Immunofluorescence, Staining, Expressing, Control

MSC-derived sEVs restore basal and non-mitochondrial respiration in septic mouse cerebellum Cellular respiration measured with Seahorse technology in mice. (A) Basal respiration decreases in sepsis [236.1 ± 19.1 vs. 311.0 ± 38.2 (∗ p = 0.0226)], but significantly improves with MSC-derived sEV treatment (332.4 ± 40.4, ∗ p = 0.0337 ) to levels similar to controls (311.0 ± 38.2, p = 0.3146 ) . (B) Cerebellar tissue shows lower maximum respiration in sepsis that is trending higher with MSC-derived sEV administration but did not reach significance ( p = 0.07). (C) Non-mitochondrial respiration i.e., OCR attributable to ROS production or pentose phosphate pathway increases under septic conditions [268.2 ± 36.4 vs.127.3 ± 19.3 (∗∗∗ p = 0.0051)], but not with treatment (79.3 ± 8.6, ∗∗∗ p = 0.0048), indicating that MSC-derived sEVs favor OXPHOS-linked ATP production. (D) Although the average ATP-linked respiration showed improvement with sEV treatment, there was no statistically significant difference among the groups, likely due to the short period of time in which observations occurred. Data are represented as mean ± SEM, one-way ANOVA. Control+media ( n = 5), Control+MSC-derived sEVs ( n = 5), Sepsis+media ( n = 5), Sepsis+MSC-derived sEVs ( n = 5). OCR: Oxygen consumption rate, ROS: reactive oxygen species, OXPHOS: oxidative phosphorylation, ATP: adenosine triphosphate, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant.

Figure Legend Snippet: MSC-derived sEVs restore basal and non-mitochondrial respiration in septic mouse cerebellum Cellular respiration measured with Seahorse technology in mice. (A) Basal respiration decreases in sepsis [236.1 ± 19.1 vs. 311.0 ± 38.2 (∗ p = 0.0226)], but significantly improves with MSC-derived sEV treatment (332.4 ± 40.4, ∗ p = 0.0337 ) to levels similar to controls (311.0 ± 38.2, p = 0.3146 ) . (B) Cerebellar tissue shows lower maximum respiration in sepsis that is trending higher with MSC-derived sEV administration but did not reach significance ( p = 0.07). (C) Non-mitochondrial respiration i.e., OCR attributable to ROS production or pentose phosphate pathway increases under septic conditions [268.2 ± 36.4 vs.127.3 ± 19.3 (∗∗∗ p = 0.0051)], but not with treatment (79.3 ± 8.6, ∗∗∗ p = 0.0048), indicating that MSC-derived sEVs favor OXPHOS-linked ATP production. (D) Although the average ATP-linked respiration showed improvement with sEV treatment, there was no statistically significant difference among the groups, likely due to the short period of time in which observations occurred. Data are represented as mean ± SEM, one-way ANOVA. Control+media ( n = 5), Control+MSC-derived sEVs ( n = 5), Sepsis+media ( n = 5), Sepsis+MSC-derived sEVs ( n = 5). OCR: Oxygen consumption rate, ROS: reactive oxygen species, OXPHOS: oxidative phosphorylation, ATP: adenosine triphosphate, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant.

Techniques Used: Derivative Assay, Control

MSC-derived sEVs alter the activation of miRNAs in the septic cerebellum (A) Predicted inhibited (gray) miRNAs (determined by directional z-scores) in septic mice compared to controls. Ranked based on p value as determined using Fisher’s exact test. Most miRNAs of interest are inhibited, indicating that they do not have any predicted inhibitory effects on their target mRNA. (B) Predicted activated (green) and inhibited (gray) miRNAs (determined by directional z-scores) in septic MSC-derived sEV-treated mice compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. Several miRNAs inhibited in septic mice that received sEV-depleted media were predicted to be activated in the septic mice that received MSC-derived sEVs. Source data are provided as a source d file.

Figure Legend Snippet: MSC-derived sEVs alter the activation of miRNAs in the septic cerebellum (A) Predicted inhibited (gray) miRNAs (determined by directional z-scores) in septic mice compared to controls. Ranked based on p value as determined using Fisher’s exact test. Most miRNAs of interest are inhibited, indicating that they do not have any predicted inhibitory effects on their target mRNA. (B) Predicted activated (green) and inhibited (gray) miRNAs (determined by directional z-scores) in septic MSC-derived sEV-treated mice compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. Several miRNAs inhibited in septic mice that received sEV-depleted media were predicted to be activated in the septic mice that received MSC-derived sEVs. Source data are provided as a source d file.

Techniques Used: Derivative Assay, Activation Assay

Image Search Results

Journal: iScience

Article Title: Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy

doi: 10.1016/j.isci.2024.110573

Figure Lengend Snippet: MSC-derived sEV treatment decreases clinical severity scores in murine sepsis (A) Diagram of murine cecal slurry model. Mice were injected with cecal slurry IP, to induce polymicrobial sepsis. At 6 h post-injection, MSC-derived sEVs or sEV-depleted media were administered via tail vein injection. When mice reached a sepsis score of 15 or above or at 24 h post-IP injection, the brain tissue was harvested. (B) MSC-derived sEV treatment ( n = 26) in mice 6 h after the onset of sepsis resulted in improved disease overall severity score as compared with the untreated septic mice ( n = 19) (∗∗∗ p = 0.0005) and lower peak scores (∗∗∗∗ p < 0.0001). (C) MSC-derived sEV treatment improved scores at 24 h in neurological-only parameters (i.e., level of consciousness, activity, response to stimulus) as compared with the untreated septic mice (∗ p = 0.01). Data are represented as mean ± SEM, one-way ANOVA. ANOVA: Analysis of Variance, IP: intraperitoneally, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant.

Article Snippet: MSC-derived sEVs were isolated from human adipose-derived MSC cell cultures (ADMSC) obtained from Zen-Bio (Durham, NC) for the purpose of this research.

Techniques: Derivative Assay, Injection, Activity Assay

Journal: iScience

Article Title: Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy

doi: 10.1016/j.isci.2024.110573

Figure Lengend Snippet: Sepsis-induced cerebellar injury is reversed by MSC-derived sEVs (A–D) Representative photomicrographs of H&E and TUNEL staining in the mouse cerebellum show significant histopathological alterations during sepsis. Compared to controls, which exhibited intact cellular architecture with clear, rounded nuclei, the septic mouse cerebellum displayed (A) significant histopathological alterations including shrunken PCs, pyknotic nuclei (black arrows), perineuronal vacuole formation (Materials and Methods: Tissue processing and histological assessment) and (B) increased TUNEL labeled cells (white arrows) indicating DNA fragmentation and cell death. Overall, sepsis resulted in (C) increased neuropathological score and (D) TUNEL+ cells (∗∗∗∗ p < 0.0001 and ∗∗∗∗ p < 0.0001) which both improved with MSC-derived sEV treatment (∗ p = 0.0155 and ∗∗ p = 0.0063). Data are represented as mean ± SEM, one-way ANOVA. Scale bar = 10 μm, Control ( n = 7), Sepsis+media ( n = 8), Sepsis+MSC-derived sEVs ( n = 8). ANOVA: Analysis of Variance, DNA: Deoxyribonucleic Acid, H&E: Hematoxylin and Eosin, NS: non-significant, PC: Purkinje cells, TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles.

Article Snippet: MSC-derived sEVs were isolated from human adipose-derived MSC cell cultures (ADMSC) obtained from Zen-Bio (Durham, NC) for the purpose of this research.

Techniques: Derivative Assay, TUNEL Assay, Staining, Labeling, Control, End Labeling

Journal: iScience

Article Title: Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy

doi: 10.1016/j.isci.2024.110573

Figure Lengend Snippet: RNA-seq reveals MSC-derived sEV-induced changes in cerebellar transcriptome following sepsis (A and B) Predicted activated (green) and inhibited (gray) causal networks and canonical pathways (determined by directional z-scores) in septic mice treated with MSC-derived sEVs compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. (C) Predicted increases (green) and decreases (gray) in cell and molecular functions (determined by directional z-scores) in septic mice treated with MSC-derived sEVs compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. (D) Predicted activated (green) and inhibited (gray) upstream regulators (determined by directional z-scores) in in septic mice treated with MSC-derived sEVs compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. (E) Heatmap of most significantly predicted upstream regulators when septic mice treated with MSC-derived sEVs are compared to untreated septic mice. Boxes are colorized with z-scores (green = activated, gray = inactivated). Source data are provided as a source data file.

Article Snippet: MSC-derived sEVs were isolated from human adipose-derived MSC cell cultures (ADMSC) obtained from Zen-Bio (Durham, NC) for the purpose of this research.

Techniques: RNA Sequencing Assay, Derivative Assay

Journal: iScience

Article Title: Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy

doi: 10.1016/j.isci.2024.110573

Figure Lengend Snippet: MSC-derived sEVs affect cytokine concentration in septic mouse cerebellum TNF-α and IL-17α assessed by immunofluorescence. (A) Representative photomicrograph of TNF-α, PV and IL-17α staining in low (x1.4, left) and high (×60, right) magnification of the area included in the hatched box. TNF-α was expressed and co-localized with the PC and their dendrites. (B and C) TNF-α expression significantly increased in SE compared to controls (5.2 ± 1.1 vs. 1.4 ± 0.2, p = 0.0085), however, treatment with MSC-derived sEVs restored its expression by more than 50% (1.9 ± 0.2, p = 0.03). Notably, TNF-α was not expressed in parvalbumin (PV)+ interneurons (a and c) that surround the PCs. (D) The expression of IL-17α was similar in control and septic mice (5.62E+09 ± 2.7E+08 vs. 7.8E+09 ± 3.7E+08, p = 0.1096), however, treatment with MSC-derived sEVs doubled its expression (1.52E+10 ± 1.3E+09, p =<0.0001). Data are represented as mean ± SEM, one-way ANOVA. Scale bar = 10 μm, Control ( n = 6), Sepsis+media [for TNF-α ( n = 7) and IL-17α ( n = 8)], Sepsis+MSC-derived sEVs [(for TNF-α ( n = 5) and IL-17α ( n = 6)]. MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant, TNFα: tumor necrosis factor alpha, IL-17α: interleukin 17 alpha, ANOVA: Analysis of Variance, PV: parvalbumin.

Article Snippet: MSC-derived sEVs were isolated from human adipose-derived MSC cell cultures (ADMSC) obtained from Zen-Bio (Durham, NC) for the purpose of this research.

Techniques: Derivative Assay, Concentration Assay, Immunofluorescence, Staining, Expressing, Control

Journal: iScience

Article Title: Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy

doi: 10.1016/j.isci.2024.110573

Figure Lengend Snippet: MSC-derived sEVs restore basal and non-mitochondrial respiration in septic mouse cerebellum Cellular respiration measured with Seahorse technology in mice. (A) Basal respiration decreases in sepsis [236.1 ± 19.1 vs. 311.0 ± 38.2 (∗ p = 0.0226)], but significantly improves with MSC-derived sEV treatment (332.4 ± 40.4, ∗ p = 0.0337 ) to levels similar to controls (311.0 ± 38.2, p = 0.3146 ) . (B) Cerebellar tissue shows lower maximum respiration in sepsis that is trending higher with MSC-derived sEV administration but did not reach significance ( p = 0.07). (C) Non-mitochondrial respiration i.e., OCR attributable to ROS production or pentose phosphate pathway increases under septic conditions [268.2 ± 36.4 vs.127.3 ± 19.3 (∗∗∗ p = 0.0051)], but not with treatment (79.3 ± 8.6, ∗∗∗ p = 0.0048), indicating that MSC-derived sEVs favor OXPHOS-linked ATP production. (D) Although the average ATP-linked respiration showed improvement with sEV treatment, there was no statistically significant difference among the groups, likely due to the short period of time in which observations occurred. Data are represented as mean ± SEM, one-way ANOVA. Control+media ( n = 5), Control+MSC-derived sEVs ( n = 5), Sepsis+media ( n = 5), Sepsis+MSC-derived sEVs ( n = 5). OCR: Oxygen consumption rate, ROS: reactive oxygen species, OXPHOS: oxidative phosphorylation, ATP: adenosine triphosphate, MSC-derived sEV: mesenchymal stem cell-derived small extracellular vesicles, NS: non-significant.

Article Snippet: MSC-derived sEVs were isolated from human adipose-derived MSC cell cultures (ADMSC) obtained from Zen-Bio (Durham, NC) for the purpose of this research.

Techniques: Derivative Assay, Control

Journal: iScience

Article Title: Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy

doi: 10.1016/j.isci.2024.110573

Figure Lengend Snippet: MSC-derived sEVs alter the activation of miRNAs in the septic cerebellum (A) Predicted inhibited (gray) miRNAs (determined by directional z-scores) in septic mice compared to controls. Ranked based on p value as determined using Fisher’s exact test. Most miRNAs of interest are inhibited, indicating that they do not have any predicted inhibitory effects on their target mRNA. (B) Predicted activated (green) and inhibited (gray) miRNAs (determined by directional z-scores) in septic MSC-derived sEV-treated mice compared to untreated septic mice. Ranked based on p value as determined using Fisher’s exact test. Several miRNAs inhibited in septic mice that received sEV-depleted media were predicted to be activated in the septic mice that received MSC-derived sEVs. Source data are provided as a source d file.

Article Snippet: MSC-derived sEVs were isolated from human adipose-derived MSC cell cultures (ADMSC) obtained from Zen-Bio (Durham, NC) for the purpose of this research.

Techniques: Derivative Assay, Activation Assay

( A ) Gene construct of adenovirus vector containing the gene for CGRP 8–37 . The CGRP 8–37 fragment was inserted downstream of the signal sequence of peptidylglycine-amidating monooxygenase (ssPAM/pGEMT). This arrangement facilitates the amidation and secretion of CGRP 8–37 . ( B ) MSC were isolated from human infrapatellar fat pad (IFP), transduced with gene construct, and sorted by FACS cell sorting to generate aCGRP IFP-MSC. aCGRP IFP-MSC sEVs were isolated and characterized for their miRNA cargo. Functional assessment of aCGRP IFP-MSC sEVs was performed by macrophage polarization and cortical neurons neuroinflammation assays.

Journal: Cells

Article Title: Modification of Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles by Calcitonin Gene Related Peptide (CGRP) Antagonist: Potential Implications for Inflammation and Pain Reversal

doi: 10.3390/cells13060484

Figure Lengend Snippet: ( A ) Gene construct of adenovirus vector containing the gene for CGRP 8–37 . The CGRP 8–37 fragment was inserted downstream of the signal sequence of peptidylglycine-amidating monooxygenase (ssPAM/pGEMT). This arrangement facilitates the amidation and secretion of CGRP 8–37 . ( B ) MSC were isolated from human infrapatellar fat pad (IFP), transduced with gene construct, and sorted by FACS cell sorting to generate aCGRP IFP-MSC. aCGRP IFP-MSC sEVs were isolated and characterized for their miRNA cargo. Functional assessment of aCGRP IFP-MSC sEVs was performed by macrophage polarization and cortical neurons neuroinflammation assays.

Article Snippet: MSC-derived sEVs mediate various biological functions attributed to MSC, such as tissue regeneration, intercellular communication, modulation of immunity and cell signaling [ ].

Techniques: Construct, Plasmid Preparation, Sequencing, Isolation, Transduction, FACS, Functional Assay

( A ) FACS sorting of GFP-labelled AAV CGRP 8–37 transduced IFP- MSC (n = 5). Cell sorting of transduced cells resulted in the purification of an aCGRP IFP-MSC subpopulation. ( B ) aCGRP IFP-MSC showed similar fibroblast-like morphology, but lower clonogenic capacity (72 ± 42 CFU-Fs) to non-transduced IFP-MSC. ( C ) aCGRP IFP-MSC showed high expression levels of common MSC-defining markers (CD73, CD90, CD105, CD146, CD10, HLA-DR). CD10 expression was similarly high (>95%) whereas CD146 showed reduced expression compared to non-transduced IFP-MSC. ( D ) aCGRP IFP-MSC sEVs showed high purity and <200 nm sizes. CD63 + -selected sEVs showed high positivity for CD9 marker. ( E ) Immunostaining of HEK 293 cells after incubation with aCGRP IFP-MSC sEVs. Top: Detection of AAV protein in HEK cells incubated with different concentration range of sEVs, Middle: Detection of CGRP protein in HEK cells incubated with different concentration range of sEVs, and bottom: Lower magnification of HEK cells after incubation with sEVs from recombinant MSC (left) and control, sEVs from no recombinant MSC. Plots: Top: Integrated density of AAV signal. aCGRP IFP-MSC sEVs were used at 30 μg/mL (30), 50 μg/mL (50) and 80 μg/mL (80) concentrations. * p < 0.05, ** p < 0.01, and bottom: Integrated density of CGRP signal. * p < 0.05, ** p < 0.01, *** p < 0.001.

Journal: Cells

doi: 10.3390/cells13060484

Figure Lengend Snippet: ( A ) FACS sorting of GFP-labelled AAV CGRP 8–37 transduced IFP- MSC (n = 5). Cell sorting of transduced cells resulted in the purification of an aCGRP IFP-MSC subpopulation. ( B ) aCGRP IFP-MSC showed similar fibroblast-like morphology, but lower clonogenic capacity (72 ± 42 CFU-Fs) to non-transduced IFP-MSC. ( C ) aCGRP IFP-MSC showed high expression levels of common MSC-defining markers (CD73, CD90, CD105, CD146, CD10, HLA-DR). CD10 expression was similarly high (>95%) whereas CD146 showed reduced expression compared to non-transduced IFP-MSC. ( D ) aCGRP IFP-MSC sEVs showed high purity and <200 nm sizes. CD63 + -selected sEVs showed high positivity for CD9 marker. ( E ) Immunostaining of HEK 293 cells after incubation with aCGRP IFP-MSC sEVs. Top: Detection of AAV protein in HEK cells incubated with different concentration range of sEVs, Middle: Detection of CGRP protein in HEK cells incubated with different concentration range of sEVs, and bottom: Lower magnification of HEK cells after incubation with sEVs from recombinant MSC (left) and control, sEVs from no recombinant MSC. Plots: Top: Integrated density of AAV signal. aCGRP IFP-MSC sEVs were used at 30 μg/mL (30), 50 μg/mL (50) and 80 μg/mL (80) concentrations. * p < 0.05, ** p < 0.01, and bottom: Integrated density of CGRP signal. * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: MSC-derived sEVs mediate various biological functions attributed to MSC, such as tissue regeneration, intercellular communication, modulation of immunity and cell signaling [ ].

Techniques: FACS, Purification, Expressing, Marker, Immunostaining, Incubation, Concentration Assay, Recombinant

( A ) 147 distinct miRNA were present in aCGRP IFP-MSC sEVs (n = 2). Nineteen highly present miRNAs are included in black-bordered box. ( B ) miRNAs present in aCGRP IFP-MSC sEVs were involved in the regulation of numerous genes and pathways. Predominantly, miRNAs present in sEVs are involved in the regulation of TGF-β/Wnt/FGFR pathways. Putative miRNA interactomes were generated using a miRNet centric network visual analytics platform. The miRNA target gene data were collected from well-annotated database miRTarBase v8.0 and miRNA-gene interactome network refining was performed with 2.0 betweenness cut-off. Values (with 34 cycles cut-off point) were represented in a topology miRNA-gene interactome network using force atlas layout and hypergeometric test algorithm.

Journal: Cells

doi: 10.3390/cells13060484

Figure Lengend Snippet: ( A ) 147 distinct miRNA were present in aCGRP IFP-MSC sEVs (n = 2). Nineteen highly present miRNAs are included in black-bordered box. ( B ) miRNAs present in aCGRP IFP-MSC sEVs were involved in the regulation of numerous genes and pathways. Predominantly, miRNAs present in sEVs are involved in the regulation of TGF-β/Wnt/FGFR pathways. Putative miRNA interactomes were generated using a miRNet centric network visual analytics platform. The miRNA target gene data were collected from well-annotated database miRTarBase v8.0 and miRNA-gene interactome network refining was performed with 2.0 betweenness cut-off. Values (with 34 cycles cut-off point) were represented in a topology miRNA-gene interactome network using force atlas layout and hypergeometric test algorithm.

Article Snippet: MSC-derived sEVs mediate various biological functions attributed to MSC, such as tissue regeneration, intercellular communication, modulation of immunity and cell signaling [ ].

Techniques: Generated, Refining

( A ) In aCGRP IFP-MSC sEVs (n = 2), 19 miRNAs cargos were highly present. These distinct miRNAs regulate genes involved in the production of cytokines, the recruitment of monocytes, and cartilage homeostasis. From these miRNAs, 7 miRNAs were associated in previous studies with significant anti-inflammatory/immunomodulatory effects in vitro and in vivo. Putative miRNA interactomes were generated using a miRNet centric network visual analytics platform. The miRNA target gene data were collected from well-annotated database miRTarBase v8.0 and miRNA-gene interactome network refining was performed with 2.0 betweenness cut-off. Values (with 34 cycles cut-off point) were represented in a topology miRNA-gene interactome network using force atlas layout and hypergeometric test algorithm. ( B ) In silico analysis revealed a functional correlation of identified miRNAs in aCGRP IFP-MSC sEVs with genes involved in M2 macrophage polarization, immunomodulatory and pain signaling, and cartilage homeostasis. The miRDB online database for prediction of functional miRNA targets has been used to correlate highly expressed target genes in macrophages with specific miRNAs identified by aCGRP IFP-MSC sEV miRNA profiling. MirTarget prediction scores are in the range of 0–100% probability, and candidate transcripts with scores ≥ 50% are presented as predicted miRNA targets in miRDB.

Journal: Cells

doi: 10.3390/cells13060484

Figure Lengend Snippet: ( A ) In aCGRP IFP-MSC sEVs (n = 2), 19 miRNAs cargos were highly present. These distinct miRNAs regulate genes involved in the production of cytokines, the recruitment of monocytes, and cartilage homeostasis. From these miRNAs, 7 miRNAs were associated in previous studies with significant anti-inflammatory/immunomodulatory effects in vitro and in vivo. Putative miRNA interactomes were generated using a miRNet centric network visual analytics platform. The miRNA target gene data were collected from well-annotated database miRTarBase v8.0 and miRNA-gene interactome network refining was performed with 2.0 betweenness cut-off. Values (with 34 cycles cut-off point) were represented in a topology miRNA-gene interactome network using force atlas layout and hypergeometric test algorithm. ( B ) In silico analysis revealed a functional correlation of identified miRNAs in aCGRP IFP-MSC sEVs with genes involved in M2 macrophage polarization, immunomodulatory and pain signaling, and cartilage homeostasis. The miRDB online database for prediction of functional miRNA targets has been used to correlate highly expressed target genes in macrophages with specific miRNAs identified by aCGRP IFP-MSC sEV miRNA profiling. MirTarget prediction scores are in the range of 0–100% probability, and candidate transcripts with scores ≥ 50% are presented as predicted miRNA targets in miRDB.

Article Snippet: MSC-derived sEVs mediate various biological functions attributed to MSC, such as tissue regeneration, intercellular communication, modulation of immunity and cell signaling [ ].

Techniques: In Vitro, In Vivo, Generated, Refining, In Silico, Functional Assay

( A , B ) Multiple immunomodulatory and reparative molecules secreted as a cargo of aCGRP IFP-MSC sEVs (n = 2). sEVs showed presence of key immunomodulatory molecules including TIMP-2, IL-8, MCP-1, IL-6, ICAM-1, sTNF-RI, MIP-1β, IL-10, and IP-10. In parallel, key reparative molecules including HGF, VEGF, EGFR, IGFBP-1, βFGF, and IGFBP-6 showed presence in aCGRP IFP-MSC sEVs. These proteins are listed in descending order based on their presence levels within sEVs. The miRDB online database for prediction of functional miRNA targets has been used to correlate highly expressed target genes in macrophages with specific miRNAs identified by aCGRP IFP-MSC sEV miRNA profiling. In terms of biological processes, various categories were highly affected and presented as % of proteins involved in a category to the total proteins detected. aCGRP IFP-MSC sEVs protein cargo have effects on PI3K-Akt signaling pathway (59%), MAPK signaling pathway (55%), Ras signaling pathway (52%), Rap1 signaling pathway (43%), cytokine-cytokine receptor interaction (24%), and Jak-STAT signaling pathway (19%). MirTarget prediction scores are in the range of 0–100% probability, and candidate transcripts with scores ≥ 50% are presented as predicted miRNA targets in miRDB.

Journal: Cells

doi: 10.3390/cells13060484

Figure Lengend Snippet: ( A , B ) Multiple immunomodulatory and reparative molecules secreted as a cargo of aCGRP IFP-MSC sEVs (n = 2). sEVs showed presence of key immunomodulatory molecules including TIMP-2, IL-8, MCP-1, IL-6, ICAM-1, sTNF-RI, MIP-1β, IL-10, and IP-10. In parallel, key reparative molecules including HGF, VEGF, EGFR, IGFBP-1, βFGF, and IGFBP-6 showed presence in aCGRP IFP-MSC sEVs. These proteins are listed in descending order based on their presence levels within sEVs. The miRDB online database for prediction of functional miRNA targets has been used to correlate highly expressed target genes in macrophages with specific miRNAs identified by aCGRP IFP-MSC sEV miRNA profiling. In terms of biological processes, various categories were highly affected and presented as % of proteins involved in a category to the total proteins detected. aCGRP IFP-MSC sEVs protein cargo have effects on PI3K-Akt signaling pathway (59%), MAPK signaling pathway (55%), Ras signaling pathway (52%), Rap1 signaling pathway (43%), cytokine-cytokine receptor interaction (24%), and Jak-STAT signaling pathway (19%). MirTarget prediction scores are in the range of 0–100% probability, and candidate transcripts with scores ≥ 50% are presented as predicted miRNA targets in miRDB.

Article Snippet: MSC-derived sEVs mediate various biological functions attributed to MSC, such as tissue regeneration, intercellular communication, modulation of immunity and cell signaling [ ].

Techniques: Functional Assay

Journal: Cells

doi: 10.3390/cells13060484

Figure Lengend Snippet: ( A ) PMA/IO-stimulated THP-1 showed similar morphology with and without aCGRP IFP-MSC sEVs treatment (n = 2). Upon exposure to aCGRP IFP-MSC sEVs, PMA/IO-stimulated THP-1 gene expression analysis showed a strong shift towards M0/M2 macrophage polarization. Notably, exposure to aCGRP IFP-MSC sEVs induced significant expression of key M2-polarization markers such as CD200R1 , BMP7 , IRF4 , IL10 , and IL12A . ( B ) TIC-stimulated cortical neurons showed similar morphology with and without aCGRP IFP-MSC sEVs treatment (n = 2). Upon exposure to aCGRP IFP-MSC sEVs, their molecular profiling indicated an overall reduced neuroinflammatory profile upon exposure to aCGRP IFP-MSC sEVs. From 84 genes, only 14 ( SLC6A2 , IL1B , PTGS1 , EDN1 , SCN11A , CCR2 , TLR2 , GDNF , CD4 , OPRD1 , ACE , ALOX5 , PTGES , CCL12 ) showed increased expression (>2-fold) compared to TIC-stimulated cortical neurons alone. Blue bars indicate the >2-fold expressed genes. Interestingly, 4 major genes ( MAPK8 , CD200 , MAPK1 , PTGES3 ) involved in neuropathic pain were highly down-regulated (>2-fold) upon exposure to aCGRP IFP-MSC sEVs.

Article Snippet: MSC-derived sEVs mediate various biological functions attributed to MSC, such as tissue regeneration, intercellular communication, modulation of immunity and cell signaling [ ].

Techniques: Expressing

Journal: Cardiovascular Drugs and Therapy

Article Title: The Role of Small Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Myocardial Protection: a Review of Current Advances and Future Perspectives

doi: 10.1007/s10557-023-07472-x

Figure Lengend Snippet: Major isolation methods of SEVs

Article Snippet: Injections of MSCs-derived SEVs have been shown to restore cardiac function in Sprague–Dawley (SD) rats suffering from MIRI.

Techniques: Isolation, Preserving, Molecular Weight, Blocking Assay, Size-exclusion Chromatography, Binding Assay, Polymer, Solubility, Filtration

Considerations for SEVs separation/enrichment

Journal: Cardiovascular Drugs and Therapy

Article Title: The Role of Small Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Myocardial Protection: a Review of Current Advances and Future Perspectives

doi: 10.1007/s10557-023-07472-x

Figure Lengend Snippet: Considerations for SEVs separation/enrichment

Article Snippet: Injections of MSCs-derived SEVs have been shown to restore cardiac function in Sprague–Dawley (SD) rats suffering from MIRI.

Techniques: Isolation, Molecular Weight, Size-exclusion Chromatography, High Molecular Weight, Filtration, Membrane

miRNAs delivered by MSCs-derived SEVs to regulate cardiac repair

Journal: Cardiovascular Drugs and Therapy

Article Title: The Role of Small Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Myocardial Protection: a Review of Current Advances and Future Perspectives

doi: 10.1007/s10557-023-07472-x

Figure Lengend Snippet: miRNAs delivered by MSCs-derived SEVs to regulate cardiac repair

Article Snippet: Injections of MSCs-derived SEVs have been shown to restore cardiac function in Sprague–Dawley (SD) rats suffering from MIRI.

Techniques: Activation Assay, Protein-Protein interactions

Biological characteristics of SEVs. In MSCs, the invaginated cell membrane forms vesicles, and then a variety of proteins, nucleic acids, lipids, and other substances are absorbed by the vesicles to form early endosomes and then MVBs have two pathways: one is to secrete to the extracellular space and release SEVs; another pathway is intracellular lysosomal binding degradation. There are three main ways for cardiomyocytes to absorb SEVs: membrane fusion directly, membrane endocytosis, and receptor binding on the cardiomyocyte membrane. SEVs have a double-membrane structure and are rich in DNA, miRNA, mRNA, polypeptides, enzymes, and other biological active substances. The membrane of SEVs contains tetraspanins, fusion proteins, integrins, etc.

Journal: Cardiovascular Drugs and Therapy

Article Title: The Role of Small Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Myocardial Protection: a Review of Current Advances and Future Perspectives

doi: 10.1007/s10557-023-07472-x

Figure Lengend Snippet: Biological characteristics of SEVs. In MSCs, the invaginated cell membrane forms vesicles, and then a variety of proteins, nucleic acids, lipids, and other substances are absorbed by the vesicles to form early endosomes and then MVBs have two pathways: one is to secrete to the extracellular space and release SEVs; another pathway is intracellular lysosomal binding degradation. There are three main ways for cardiomyocytes to absorb SEVs: membrane fusion directly, membrane endocytosis, and receptor binding on the cardiomyocyte membrane. SEVs have a double-membrane structure and are rich in DNA, miRNA, mRNA, polypeptides, enzymes, and other biological active substances. The membrane of SEVs contains tetraspanins, fusion proteins, integrins, etc.

Article Snippet: Injections of MSCs-derived SEVs have been shown to restore cardiac function in Sprague–Dawley (SD) rats suffering from MIRI.

Techniques: Membrane, Binding Assay

Review

Structured Review

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1) Product Images from "Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy"

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