Journal: Frontiers in Cell and Developmental Biology

Article Title: Therapeutic Mesenchymal Stem/Stromal Cells: Value, Challenges and Optimization

doi: 10.3389/fcell.2021.716853

Figure Lengend Snippet: MSC and MSC progenitors- based products with marketing approval for clinical application worldwide.

Article Snippet: Allostem , Bone regeneration , Allogeneic AD-MSCs , AlloSource , United States (2010) , Regulated under CFR 1,270, 1,271 as a human tissue. Do not require pre-market approval from the FDA. (Ref. 1; Ref. 2).

Techniques: Membrane

Journal: Scientific Reports

Article Title: Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension

doi: 10.1038/s41598-021-81244-1

Figure Lengend Snippet: Echocardiographic analysis of MSC-treated lungs at week 2 and 4. ( a ) Schematic illustration of MCT and MSC treatment experiments. MCT was subcutaneously injected into 8-week-old male rats. At 2 weeks post-MCT injection, MSCs (1 × 10 6 cells) were injected into randomized animals via the tail vein. At 4 weeks post-MCT injection, the echocardiography was performed before the animals were sacrificed for tissue analysis. ( b ) The effects of the MSC administration on right ventricular (RV) pressure and function were evaluated by echocardiography at week 2 and 4 post-MCT injection. Representative images of the short axis view of the echocardiogram showing the right and left ventricle of the rat heart. D-shaped left ventricles (LV) caused by elevated RV pressure were observed in MCT + Saline group, where the MSC injected groups had attenuated RV size and D-shaped compared with the MCT + Saline group. ( c – f ) The tricuspid regurgitation maximal pressure gradient (TR max PG), pulmonary velocity acceleration time (PVAT), tricuspid annular plane systolic excursion (TAPSE), and RV fractional area contraction (RV FAC) of each treatment group are shown. Each group was examined in n = 7 mice. Data are shown as the mean ± SD. Statistical significance is marked with 3 symbols. * for the comparison with control; $ for the comparison with the MCT + Saline group; # for the comparison with the MCT + UCB group; *, $, # P < 0.05; **, $$, ## P < 0.01; ***, $$$, ### P < 0.001 from Mann–Whitney test; CON: control ; MCT: monocrotaline; MSC: mesenchymal stem cell; RV: right ventricule; LV: left ventricle; AD: adipose tissue-derived; BM: bone-marrow-derived; UCB: umbilical cord blood-derived; TR max PG: tricuspid regurgitation max pressure gradient; PVAT: pulmonary velocity acceleration time; TAPSE: tricuspid annular plane systolic excursion; RV FAC: right ventricular fractional area contraction.

Article Snippet: AD and UCB-derived MSCs were purchased from Medipost (Seongnam, Korea) and BM-derived MSCs were purchased from Cefobio (Seoul, Korea).

Techniques: Injection, MANN-WHITNEY, Derivative Assay

Journal: Scientific Reports

Article Title: Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension

doi: 10.1038/s41598-021-81244-1

Figure Lengend Snippet: Inhibitory effects of UCB-MSCs on innate/adaptive immunity and inflammation. ( a , b ) immunostainings and mRNA expression levels of the markers for M1 macrophages ( Cd80 ), and M2 macrophages ( Cd206 ). ( c , d ) immunostainings and mRNA expression levels of inflammatory cytokines of M1 ( Tnf-α ) and M2 macrophages ( Tgf-β ). ( e , f ) immunostsainings and mRNA expression levels of the markers for T cells ( Cd8 ) and B cells ( Cd20 ). ( g , h ) immunostainings and mRNA expression levels of the inflammatory cytokines in T cells ( IL-10 ) and B cells ( IL-8 ). Data are shown as the mean ± SD. Statistical significance is marked with 3 symbols. * for the comparison with the control; $ for the comparison with the MCT + Saline group; # for the comparison with the MCT + UCB group; *, $, # P < 0.05; **, $$, ## P < 0.01; ***, $$$, ### P < 0.001 by Mann–Whitney test; MCT: monocrotaline; CON: control; AD: adipose tissue-derived; BM: bone-marrow-derived; UCB: umbilical cord blood-derived.

Article Snippet: AD and UCB-derived MSCs were purchased from Medipost (Seongnam, Korea) and BM-derived MSCs were purchased from Cefobio (Seoul, Korea).

Techniques: Expressing, MANN-WHITNEY, Derivative Assay

Journal: Scientific Reports

Article Title: Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension

doi: 10.1038/s41598-021-81244-1

Figure Lengend Snippet: Cellular processes affected by AD-, BD-, and UCB-MSCs in the MCT model. ( a ) Venn diagram showing the relationships among the DEGs from the four indicated comparisons. Numbers in parentheses represent the numbers of DEGs identified from the comparisons. ( b ) Heat map showing the differential expression of the genes in G1–4. The colors indicate up-regulation (red) and down-regulation (green) in MCT, and AD-, BD-, and UCB-MSCs, compared to the control conditions in the corresponding comparisons. The color bar represents the gradient of the log 2 -fold-changes in the comparisons. Numbers in parentheses represent the numbers of DEGs in the indicated groups. ( c ) GOBPs represented by the genes in G1–4. The color bar represents the gradient of − log 10 (p), where p is the significance of the individual GOBPs that are enriched by the DEGs in G1–4. The heat map was generated using MATLAB (imagesc.m in R2019a; www.mathworks.com/ ). DEG: differentially expressed genes; GOBP: gene ontology biological processes; MCT: monocrotaline; CON: control; AD: adipose tissue-derived; BM: bone-marrow-derived; UCB: umbilical cord blood-derived.

Article Snippet: AD and UCB-derived MSCs were purchased from Medipost (Seongnam, Korea) and BM-derived MSCs were purchased from Cefobio (Seoul, Korea).

Techniques: Expressing, Generated, Derivative Assay

Journal: Scientific Reports

Article Title: Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension

doi: 10.1038/s41598-021-81244-1

Figure Lengend Snippet: Inhibitory effects of UCB-MSC administration on the immune and inflammatory responses. ( a , b ) GOBPs represented by the upregulated ( a ) and downregulated ( b ) genes predominantly by UCB-MSCs. Enrichment significance (p) for each GOBP is displayed in − log 10 (p). ( c , d ) Heat maps showing the differential expression of the genes involved in the inflammatory ( c ) and immune responses ( d ). The color bar represents the gradient of the log 2 -fold-changes in the comparisons. The heat map was generated using MATLAB (imagesc.m in R2019a; www.mathworks.com/ ). ( e ) A network model describing interactions among the predominantly upregulated genes by UCB-MSCs. Node center and boundary colors represent upregulation (red) and downregulation (green) by MCT and UCB-MSCs, respectively. Solid and dotted arrows (or inhibition symbols) denote direct and indirect activations (or inhibition), respectively. The color bar represents the gradient of log 2 -fold-changes in the corresponding comparison (MCT + Saline/CON or MCT + UCB/MCT + Saline). The network model was generated using Cytoscape software (v.3.3.0; www.cytoscape.org/ ). ( f ) Confirmation of the predominant upregulation of the indicated three representative genes involved in the inflammatory and immune responses by qRT-PCR. The expression levels were normalized with respect to those in the control group. The normalized data are expressed as the mean ± SD. Statistical significance is marked with 3 symbols. * for the comparison with the control; $ for the comparison with the MCT + Saline group; # for the comparison with the MCT + UCB group; *, $, # P < 0.05; **, $$, ## P < 0.01; ***, $$$, ### P < 0.001 by Mann–Whitney test; GOBP: gene ontology biological processes; MCT: monocrotaline; CON: control; AD: adipose tissue-derived; BM: bone-marrow-derived; UCB: umbilical cord blood-derived.

Article Snippet: AD and UCB-derived MSCs were purchased from Medipost (Seongnam, Korea) and BM-derived MSCs were purchased from Cefobio (Seoul, Korea).

Techniques: Expressing, Generated, Inhibition, Software, Quantitative RT-PCR, MANN-WHITNEY, Derivative Assay

Journal: Scientific Reports

Article Title: Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension

doi: 10.1038/s41598-021-81244-1

Figure Lengend Snippet: Inhibitory effects of UCB-MSCs on PAH progression. ( a ) Network model describing modulation of PAH and inflammation-related signaling pathways by the MSCs. Node center and boundary colors represent upregulation (red) and downregulation (green) by MCT and UCB-MSCs, respectively. The color bar represents the gradient of log 2 -fold-changes in the corresponding comparison (MCT + Saline/CON or MCT + UCB/MCT + Saline). The stacked bar shows which MSC significantly affected the corresponding genes: for example, ‘U’ in purple indicates the corresponding gene was identified as a DEG in the comparison of MCT + UCB versus MCT + Saline. The color bar denotes the gradient of the log 2 -fold-changes in the four comparisons. Edges represent the protein–protein interactions (gray) between the genes in the network model, which were collected from the five interactome databases. Solid and dotted arrows (or inhibition symbols) denote direct and indirect activations (or inhibition), respectively. The network model was generated using Cytoscape software (v.3.3.0; www.cytoscape.org/ ). ( b ) Confirmation of the differential expression of the indicated representative genes involved in the PAH and inflammation-related pathways. The expression levels were normalized with respect to those in the CON group. The normalized data are expressed as the mean ± SD.* for the comparison with the control; $ for the comparison with the MCT + Saline group; # for the comparison with the MCT + UCB group; *, $, # P < 0.05; **, $$, ## P < 0.01; ***, $$$, ### P < 0.001 by Mann–Whitney test; DEG = differentially expressed genes; MCT = monocrotaline; CON = control; AD = adipose tissue-derived; BM = bone-marrow-derived; UCB = umbilical cord blood-derived.

Article Snippet: AD and UCB-derived MSCs were purchased from Medipost (Seongnam, Korea) and BM-derived MSCs were purchased from Cefobio (Seoul, Korea).

Techniques: Inhibition, Generated, Software, Expressing, MANN-WHITNEY, Derivative Assay