scholarly journals Paracrine stimulation of perinatal lung functional and structural maturation by mesenchymal stem cells.

2020 ◽  
Author(s):  
Janine Obendorf ◽  
Claire Fabian ◽  
Ulrich H. Thome ◽  
Mandy Laube
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Mrna Expression ◽  
Surfactant Protein ◽  
Lung Epithelial Cells ◽  
Na Channel ◽  
Na Transport ◽  
Lung Maturation ◽  
Fetal Lungs

Abstract Background: Mesenchymal stem cells (MSCs) were shown to harbor therapeutic potential in models of respiratory diseases, such as Bronchopulmonary Dysplasia (BPD), the most common sequel of preterm birth. In these studies cells or animals were challenged with hyperoxia or other injury-inducing agents. However, little is known about the effect of MSCs on immature fetal lungs and whether MSCs are able to improve lung maturity, which may alleviate lung developmental arrest in BPD. Methods: We aimed to determine if conditioned medium (CM) of MSCs stimulates functional and structural lung maturation. As a measure of functional maturation, Na + transport in primary fetal distal lung epithelial cells (FDLE) was studied in Ussing chambers. Na + transporter and surfactant protein mRNA expression was determined by qRT-PCR. Structural maturation was assessed by microscopy in fetal rat lung explants. Results: MSC-CM strongly increased the activity of the epithelial Na + channel (ENaC) and the Na,K-ATPase as well as their mRNA expression. Branching and growth of fetal lung explants, and surfactant protein mRNA expression were enhanced by MSC-CM. Epithelial integrity and metabolic activity of FDLE cells were not influenced by MSC-CM. Since MSC’ actions are mainly attributed to paracrine signaling, prominent lung growth factors were blocked. None of the tested growth factors (VEGF, BMP, PDGF, EGF, TGF-β, FGF, HGF) contributed to the MSC-induced increase of Na + transport. In contrast, inhibition of PI3-K/AKT and Rac1 signaling reduced MSC-CM efficacy, suggesting an involvement of these pathways in the MSC-CM-induced Na + transport. Conclusion: The results demonstrate that MSC-CM strongly stimulated functional and structural maturation of fetal lungs. These effects were at least partially mediated by the PI3-K/AKT and Rac1 signaling pathway. Thus MSCs not only repair a deleterious tissue environment, but also target lung cellular immaturity itself.

scholarly journals Paracrine stimulation of perinatal lung functional and structural maturation by mesenchymal stem cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Janine Obendorf ◽  
Claire Fabian ◽  
Ulrich H. Thome ◽  
Mandy Laube
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Mrna Expression ◽  
Therapeutic Potential ◽  
Surfactant Protein ◽  
Lung Epithelial Cells ◽  
Lung Maturation ◽  
Ussing Chambers ◽  
Fetal Lungs

Abstract Background Mesenchymal stem cells (MSCs) were shown to harbor therapeutic potential in models of respiratory diseases, such as bronchopulmonary dysplasia (BPD), the most common sequel of preterm birth. In these studies, cells or animals were challenged with hyperoxia or other injury-inducing agents. However, little is known about the effect of MSCs on immature fetal lungs and whether MSCs are able to improve lung maturity, which may alleviate lung developmental arrest in BPD. Methods We aimed to determine if the conditioned medium (CM) of MSCs stimulates functional and structural lung maturation. As a measure of functional maturation, Na+ transport in primary fetal distal lung epithelial cells (FDLE) was studied in Ussing chambers. Na+ transporter and surfactant protein mRNA expression was determined by qRT-PCR. Structural maturation was assessed by microscopy in fetal rat lung explants. Results MSC-CM strongly increased the activity of the epithelial Na+ channel (ENaC) and the Na,K-ATPase as well as their mRNA expression. Branching and growth of fetal lung explants and surfactant protein mRNA expression were enhanced by MSC-CM. Epithelial integrity and metabolic activity of FDLE cells were not influenced by MSC-CM. Since MSC’s actions are mainly attributed to paracrine signaling, prominent lung growth factors were blocked. None of the tested growth factors (VEGF, BMP, PDGF, EGF, TGF-β, FGF, HGF) contributed to the MSC-induced increase of Na+ transport. In contrast, inhibition of PI3-K/AKT and Rac1 signaling reduced MSC-CM efficacy, suggesting an involvement of these pathways in the MSC-CM-induced Na+ transport. Conclusion The results demonstrate that MSC-CM strongly stimulated functional and structural maturation of the fetal lungs. These effects were at least partially mediated by the PI3-K/AKT and Rac1 signaling pathway. Thus, MSCs not only repair a deleterious tissue environment, but also target lung cellular immaturity itself.

scholarly journals Paracrine Stimulation of Perinatal Lung Functional and Structural Maturation by Mesenchymal Stem Cells.

2020 ◽  
Author(s):  
Janine Obendorf ◽  
Claire Fabian ◽  
Ulrich H. Thome ◽  
Mandy Laube
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Mrna Expression ◽  
Therapeutic Potential ◽  
Surfactant Protein ◽  
Lung Epithelial Cells ◽  
Lung Maturation ◽  
Ussing Chambers ◽  
Fetal Lungs

Abstract Background: Mesenchymal stem cells (MSCs) were shown to harbor therapeutic potential in models of respiratory diseases, such as Bronchopulmonary Dysplasia (BPD), the most common sequel of preterm birth. In these studies cells or animals were challenged with hyperoxia or other injury-inducing agents. However, little is known about the effect of MSCs on immature fetal lungs and whether MSCs are able to improve lung maturity, which may alleviate lung developmental arrest in BPD.Methods: We aimed to determine if conditioned medium (CM) of MSCs stimulates functional and structural lung maturation. As a measure of functional maturation, Na+ transport in primary fetal distal lung epithelial cells (FDLE) was studied in Ussing chambers. Na+ transporter and surfactant protein mRNA expression was determined by qRT-PCR. Structural maturation was assessed by microscopy in fetal rat lung explants.Results: MSC-CM strongly increased the activity of the epithelial Na+ channel (ENaC) and the Na,K-ATPase as well as their mRNA expression. Branching and growth of fetal lung explants, and surfactant protein mRNA expression were enhanced by MSC-CM. Epithelial integrity and metabolic activity of FDLE cells were not influenced by MSC-CM. Since MSC’ actions are mainly attributed to paracrine signaling, prominent lung growth factors were blocked. None of the tested growth factors (VEGF, BMP, PDGF, EGF, TGF-β, FGF, HGF) contributed to the MSC-induced increase of Na+ transport. In contrast, inhibition of PI3-K/AKT and Rac1 signaling reduced MSC-CM efficacy, suggesting an involvement of these pathways in the MSC-CM-induced Na+ transport.Conclusion: The results demonstrate that MSC-CM strongly stimulated functional and structural maturation of fetal lungs. These effects were at least partially mediated by the PI3‑K/AKT and Rac1 signaling pathway. Thus MSCs not only repair a deleterious tissue environment, but also target lung cellular immaturity itself.

scholarly journals Comparative analysis of canine mesenchymal stem cells and bone marrow-derived mononuclear cells

2021 ◽  
Vol 14 (4) ◽  
pp. 1028-1037
Author(s):  
Noritaka Maeta ◽  
Katsutoshi Tamura ◽  
Fuuna Ezuka ◽  
Hiroshi Takemitsu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Similar Expression

Background and Aim: Mesenchymal stem cells (MSCs), which have multi-lineage differentiation potentials, are a promising source for regenerative medicine. However, the focus of study of MSCs is shifting from the characterization of the differentiation potential to their secretion potential for cell transplantation. Tissue regeneration and the attenuation of immune responses are thought to be affected by the secretion of multiple growth factors and cytokines by MSCs. However, the secretion potential of MSCs profiling remains incompletely characterized. In this study, we focused on the secretion ability related and protein mRNA expression of dog adipose tissue-derived MSCs (AT-MSC), bone marrow (BM)-derived MSCs, and BM-derived mononuclear cells (BM-MNC). Materials and Methods: Real-time polymerase chain reaction analyses revealed mRNA expression of nine growth factors and seven interleukins in these types of cells and three growth factors protein expression were determined using Enzyme-linked immunosorbent assay. Results: For the BM-MNC growth factors, the mRNA expression of transforming growth factor-β (TGF-β) was the highest. For the BM-derived MSC (BM-MSC) and AT-MSC growth factors, the mRNA expression of vascular endothelial growth factor (VEGF) was highest. BM-MSCs and AT-MSCs showed similar expression profiles. In contrast, BM-MNCs showed unique expression profiles for hepatocyte growth factor and epidermal growth factor. The three types of cells showed a similar expression of TGF-β. Conclusion: We conclude that expression of cytokine proteins and mRNAs suggests involvement in tissue repair and protection.

scholarly journals Effects of High Glucose Concentration on Pericyte-Like Differentiated Human Adipose-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 22 (9) ◽  
pp. 4604
Author(s):  
Giuliana Mannino ◽  
Anna Longo ◽  
Florinda Gennuso ◽  
Carmelina Daniela Anfuso ◽  
Gabriella Lupo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Angiogenic Factors ◽  
Diabetic Patients ◽  
Ros Production ◽  
Migration Ability ◽  
And Migration

A pericyte-like differentiation of human adipose-derived mesenchymal stem cells (ASCs) was tested in in vitro experiments for possible therapeutic applications in cases of diabetic retinopathy (DR) to replace irreversibly lost pericytes. For this purpose, pericyte-like ASCs were obtained after their growth in a specific pericyte medium. They were then cultured in high glucose conditions to mimic the altered microenvironment of a diabetic eye. Several parameters were monitored, especially those particularly affected by disease progression: cell proliferation, viability and migration ability; reactive oxygen species (ROS) production; inflammation-related cytokines and angiogenic factors. Overall, encouraging results were obtained. In fact, even after glucose addition, ASCs pre-cultured in the pericyte medium (pmASCs) showed high proliferation rate, viability and migration ability. A considerable increase in mRNA expression levels of the anti-inflammatory cytokines transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) was observed, associated with reduction in ROS production, and mRNA expression of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and angiogenic factors. Finally, a pmASC-induced better organization of tube-like formation by retinal endothelial cells was observed in three-dimensional co-culture. The pericyte-like ASCs obtained in these experiments represent a valuable tool for the treatment of retinal damages occurring in diabetic patients.

scholarly journals Hsp20-Engineered Mesenchymal Stem Cells are Resistant to Oxidative Stress Via Enhanced Activation of Akt and Increased Secretion of Growth Factors

Stem Cells ◽  
2009 ◽  
pp. N/A-N/A ◽  
Author(s):  
Xiaohong Wang ◽  
Tiemin Zhao ◽  
Wei Huang ◽  
Tao Wang ◽  
Jiang Qian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors

A comprehensive cancer-associated microRNA expression profiling and proteomic analysis of human umbilical cord mesenchymal stem cell derived exosomes.

2021 ◽  
Author(s):  
Ganesan Jothimani ◽  
Surajait Pathak ◽  
Suman Dutta ◽  
Asim K. Duttaroy ◽  
Antara Banerjee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Umbilical Cord ◽  
Expression Patterns ◽  
Functional Enrichment ◽  
Human Umbilical Cord ◽  
Human Mscs ◽  
Anti Cancer

Abstract Background The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. Methods Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and cultured expanded. After that, exosomes were isolated from the hUCMSC conditioned medium. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. Results The miRNA expression profile and gene ontology (GO) depicts the differential expression patterns of high and less-expressed miRNAs that are delineated to be involved in the regulation of the apoptosis process. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. Conclusion Primary human MSCs releases miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs may have a critical influence in regulating cell death and apoptosis of cancer cells.

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