Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation
Abstract
:1. Introduction
2. Results
2.1. Phenotypic Characteristics and Evaluation of hA-MSCs
2.2. Ascites Fluid Leukocyte Phenotype
2.3. Gene Expression Profiles and Differential Expression in Human Amnion Mesenchymal Stem Cells (hA-MSCs) Cultured Alone and in Co-Culture Pools
2.4. hA-MSCs Co-Culture Shows an Increase in CD4+ Th17 Profile
2.5. The Cytokine Composition of AF from Patients with Cirrhosis after Exposure to hA-MSCs Reflects an Environment Promoting a Lymphocytic Th17 Profile
3. Discussion
4. Materials and Methods
4.1. Patient Characteristics and Ascitic Fluid Collection
4.2. Isolation and Characterization of Human Amnion-Derived Mesenchymal Stromal/Stem Cells
4.3. Leukocyte Subset Analysis of Ascitic Fluid
4.4. Isolation and Stimulation of White Blood Cell (A-WBC) Component from Ascitic Fluid (AF)
4.5. In Vitro hA-MSCs and A-WBC Co-Cultures
4.6. RNA-Seq, Library Construction, Sequencing, and Analysis
4.7. Real-Time PCR Analysis of Gene Expression by TaqMan Low Density Arrays
4.8. Pathway Enrichment Analysis
4.9. T helper (Th) Cell Profiles after Co-Culture Infection
4.10. Detection of Multiple Cytokines Secreted by Luminex
4.11. Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Th Cell Subset | Major Function | Surface Markers | Cytokines Secreted Involved in Regulation |
---|---|---|---|
TH1 | Immunity against intracellular pathogens | CD4+CXCR3+ | IFN-γ |
TH2 | Response to parasite infections | CD4+CCR4+CCR6– | IL-4, IL-5, IL-13 |
TH17 | Response to fungi and extracellular bacteria | CD4+CCR4+CCR6+ | IL-17A, IL-22 |
Patient 1 | Patient 2 | Patient 3 | Patient 4 | |
---|---|---|---|---|
Age/sex | 55/M | 62/M | 50/M | 71/M |
Creatinine mg/dL | 2 | 0.75 | 1 | 1.4 |
Total bilirubin mg/dL | 24.4 | 3.7 | 3.7 | 3.1 |
AST/ALT U/L | 82/17 | 54/36 | 29/17 | 21/14 |
Albumin gr/dL | 2.5 | 2.8 | 2.7 | 2.8 |
Sodium mmol/L | 137 | 139 | 136 | 134 |
Hemoglobin gr/dL | 8.8 | 8.1 | 9.6 | 9.9 |
Platelets U/L | 41.000 | 148.000 | 82.000 | 65.000 |
White blood count U/L | 8430 | 7340 | 7890 | 6570 |
PMN (§) U/L | 0.08 | 0.015 | 0.038 | 0.023 |
INR (#) | 1.2 | 1.7 | 1.9 | 1.3 |
Ascites | Poorly controlled | Poorly controlled | Poorly controlled | Poorly controlled |
Encephalopathy | None | None | None | None |
Child–Pugh score | 11 | 11 | 12 | 10 |
MELD score | 28 | 18 | 20 | 20 |
Marker | Conjugation | Clone | Dilution | Manufacturer |
---|---|---|---|---|
CD3 | FITC | HIT3a | 1:20 | BD Biosciences |
CD4 | PE-Cy7 | SK3 | 1:20 | Invitrogen (Waltham, MA, USA) |
CD8 | APC-Cy7 | OKT8 | 1:20 | Caprico Biotechnologies (Norcross, GA, USA) |
CD14 | APC-Cy7 | MφP9 | 1:20 | BD Biosciences |
CD15 | PerCP | HI98 | 1:20 | BD Biosciences |
CD16 | PE | 3G8 | 1:20 | BD Biosciences |
CD56 | PE | MY31 | 1:20 | BD Biosciences |
CD45 | PerCP | alone1 | 1:20 | BD Biosciences |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Pampalone, M.; Cuscino, N.; Iannolo, G.; Amico, G.; Ricordi, C.; Vitale, G.; Carcione, C.; Castelbuono, S.; Scilabra, S.D.; Coronnello, C.; et al. Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation. Int. J. Mol. Sci. 2024, 25, 2801. https://doi.org/10.3390/ijms25052801
Pampalone M, Cuscino N, Iannolo G, Amico G, Ricordi C, Vitale G, Carcione C, Castelbuono S, Scilabra SD, Coronnello C, et al. Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation. International Journal of Molecular Sciences. 2024; 25(5):2801. https://doi.org/10.3390/ijms25052801
Chicago/Turabian StylePampalone, Mariangela, Nicola Cuscino, Gioacchin Iannolo, Giandomenico Amico, Camillo Ricordi, Giampiero Vitale, Claudia Carcione, Salvatore Castelbuono, Simone Dario Scilabra, Claudia Coronnello, and et al. 2024. "Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation" International Journal of Molecular Sciences 25, no. 5: 2801. https://doi.org/10.3390/ijms25052801