scholarly journals Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1650
Author(s):  
Priscila Calle ◽  
Soraya Játiva ◽  
Selene Torrico ◽  
Angeles Muñoz ◽  
Miriam García ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Therapeutic Effect ◽  
Unilateral Ureteral Obstruction ◽  
Macrophage Cell ◽  
Chronic Injury ◽  
Macrophage Population ◽  
Kidney Fibrosis ◽  
Phagocytic Ability ◽  
Cellular Debris ◽  
Macrophage Populations

Phagocytosis is an inherent function of tissue macrophages for the removal of apoptotic cells and cellular debris during acute and chronic injury; however, the dynamics of this event during fibrosis development is unknown. We aim to prove that during the development of kidney fibrosis in the unilateral ureteral obstruction (UUO) model, there are some populations of macrophage with a reduced ability to phagocytose, and whether the infusion of a population of phagocytic macrophages could reduce fibrosis in the murine model UUO. For this purpose, we have identified the macrophage populations during the development of fibrosis and have characterized their phagocytic ability and their expression of CPT1a. Furthermore, we have evaluated the therapeutic effect of macrophages overexpressing CPT1a with high phagocytic skills. We evidenced that the macrophage population which exhibits high phagocytic ability (F4/80low-CD11b) in fibrotic animals decreases during the progression of fibrosis while the macrophage population with lower phagocytic ability (F4/80high-CD11b) in fibrotic conditions, conversely, increases and CPT1a macrophage cell therapy with a strengthening phagocytic ability is associated with a therapeutic effect on kidney fibrosis. We have developed a therapeutic approach to reduce fibrosis in the UUO model by enrichment of the kidney resident macrophage population with a higher proportion of exogenous phagocytic macrophages overexpressing CPT1a.

scholarly journals Matrix Metalloproteinase-2 Knockout and Heterozygote Mice Are Protected from Hydronephrosis and Kidney Fibrosis after Unilateral Ureteral Obstruction

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0143390 ◽  
Author(s):  
Maria K. Tveitarås ◽  
Trude Skogstrand ◽  
Sabine Leh ◽  
Frank Helle ◽  
Bjarne M. Iversen ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Matrix Metalloproteinase 2 ◽  
Kidney Fibrosis

Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction

2018 ◽  
Vol 34 (10) ◽  
pp. 1657-1668 ◽  
Author(s):  
Ying Yang ◽  
Xiaojian Feng ◽  
Xinyan Liu ◽  
Ying Wang ◽  
Min Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Unilateral Ureteral Obstruction ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pathological Feature ◽  
Kidney Fibrosis ◽  
Anti Inflammatory

AbstractBackgroundRenal fibrosis is a key pathological feature and final common pathway leading to end-stage kidney failure in many chronic kidney diseases. Myofibroblast is the master player in renal fibrosis. However, myofibroblasts are heterogeneous. Recent studies show that bone marrow-derived macrophages transform into myofibroblasts by transforming growth factor (TGF)-β-induced macrophage–myofibroblast transition (MMT) in renal fibrosis.MethodsTGF-β signaling was redirected by inhibition of β-catenin/T-cell factor (TCF) to increase β-catenin/Foxo in bone marrow-derived macrophages. A kidney fibrosis model of unilateral ureteral obstruction was performed in EGFP bone marrow chimera mouse. MMT was examined by flow cytometry analysis of GFP+F4/80+α-SMA+ cells from unilateral ureteral obstruction (UUO) kidney, and by immunofluorescent staining of bone marrow-derived macrophages in vitro. Inflammatory and anti-inflammatory cytokines were analysis by enzyme-linked immunosorbent assay.ResultsInhibition of β-catenin/TCF by ICG-001 combined with TGF-β1 treatment increased β-catenin/Foxo1, reduced the MMT and inflammatory cytokine production by bone marrow-derived macrophages, and thereby, reduced kidney fibrosis in the UUO model.ConclusionsOur results demonstrate that diversion of β-catenin from TCF to Foxo1-mediated transcription not only inhibits the β-catenin/TCF-mediated fibrotic effect of TGF-β, but also enhances its anti-inflammatory action, allowing therapeutic use of TGF-β to reduce both inflammation and fibrosis at least partially by changing the fate of bone marrow-derived macrophages.

scholarly journals Therapeutic effect of mesenchymal stem cell therapy in the LVEF, LVEDV, and LVESV after myocardial infarction

2021 ◽  
Vol 122 (11) ◽  
pp. 785-792
Author(s):  
M. M. Rabiei ◽  
K. S. Khoramgah ◽  
I. A. Darazam ◽  
S. Vafaei-Nezhad ◽  
S. Dargahi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Therapy ◽  
Therapeutic Effect ◽  
Stem Cell Therapy ◽  
Mesenchymal Stem Cell Therapy

scholarly journals Enhancing the therapeutic effect of dendritic cell therapy by oncolytic adenovirus 3 encoding CD40-ligand

2019 ◽  
Vol 30 ◽  
pp. xi14
Author(s):  
S. Zafar ◽  
D.C.A. Quixabeira ◽  
O. Hemminki ◽  
V. Cervera-Carrascon ◽  
J.M. Santos ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Cell Therapy ◽  
Therapeutic Effect ◽  
Cd40 Ligand ◽  
Oncolytic Adenovirus ◽  
Dendritic Cell Therapy

scholarly journals Transcriptomics uncovers substantial variability associated with alterations in manufacturing processes of macrophage cell therapy products

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Olga L. Gurvich ◽  
Katja A. Puttonen ◽  
Aubrey Bailey ◽  
Anssi Kailaanmäki ◽  
Vita Skirdenko ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Manufacturing Processes ◽  
Macrophage Cell

scholarly journals Ibrutinib does not prevent kidney fibrosis following acute and chronic injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julie Belliere ◽  
Audrey Casemayou ◽  
Eloïse Colliou ◽  
Hélène El Hachem ◽  
Clément Kounde ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Subsequent Development ◽  
Lymphocytic Leukemia ◽  
Inflammasome Activation ◽  
Chronic Injury ◽  
Kidney Fibrosis ◽  
Nlrp3 Inflammasome Activation ◽  
Candidate Drug ◽  
Btk Inhibitor

AbstractRecent studies suggested that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, developed for the treatment of chronic lymphocytic leukemia, may prevent NLRP3 inflammasome activation in macrophages, IL-1β secretion and subsequent development of inflammation and organ fibrosis. The role of NLRP3 has been underlined in the various causes of acute kidney injury (AKI), a pathology characterized by high morbimortality and risk of transition toward chronic kidney disease (CKD). We therefore hypothesized that the BTK-inhibitor ibrutinib could be a candidate drug for AKI treatment. Here, we observed in both an AKI model (glycerol-induced rhabdomyolysis) and a model of rapidly progressive kidney fibrosis (unilateral ureteral obstruction), that ibrutinib did not prevent inflammatory cell recruitment in the kidney and fibrosis. Moreover, ibrutinib pre-exposure led to high mortality rate owing to severer rhabdomyolysis and AKI. In vitro, ibrutinib potentiated or had no effect on the secretion of IL-1β by monocytes exposed to uromodulin or myoglobin, two danger-associated molecule patterns proteins involved in the AKI to CKD transition. According to these results, ibrutinib should not be considered a candidate drug for patients developing AKI.

scholarly journals Experience in personalized cell therapy clinical implementation for treatment of patients with primary endothelial dystrophy after phacoemulsification

2017 ◽  
Vol 10 (4) ◽  
pp. 6-12
Author(s):  
Sergey Yu Astakhov ◽  
Inna A Riks ◽  
Sanasar S Papanyan ◽  
Arkadiy A Kasparov ◽  
Evgeniya A Kasparova ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Therapeutic Effect ◽  
Corneal Edema ◽  
Treatment Method ◽  
Bullous Keratopathy ◽  
Clinical Implementation ◽  
Treatment Results ◽  
Good Therapeutic Effect ◽  
Observation Period

The article presents treatment results of the personalized cell therapy (PCT) method in patients with early post-operative bullous keratopathy which developed in eyes with pre-existing primary Fuchs’ corneal endothelial dystrophy (ED). The patented PCT consists in incubating in vitro the patient’s blood with the stimulator (polyA:polyU), collecting serum with activated leukocytes weighted in it, and introducing the obtained cell preparation in the anterior chamber of the patient’s eye. The study included 12 patients with ED and pseudophakia. The observation period ranged from 8 to 12 months. The therapeutic effect of PCT was obtained in 58.3% of cases, allowing to avoid further surgical procedures. To achieve a good therapeutic effect, several PCT sessions are recommended. To date, PCT is the only effective therapeutic treatment method for early corneal edema after phacoemulsification. (For citation: Astakhov SYu, Riks IA, Papanyan SS, et al. Experience in personalized cell therapy clinical implementation for treatment of patients with primary endothelial dystrophy after phacoemulsification. Ophthalmology Journal. 2017;10(4):6-12. doi: 10.17816/OV1046-12).

scholarly journals Yolk-sac-derived macrophages progressively expand in the mouse kidney with age

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shintaro Ide ◽  
Yasuhito Yahara ◽  
Yoshihiko Kobayashi ◽  
Sarah A Strausser ◽  
Kana Ide ◽  
...  
Keyword(s):  
Elderly Population ◽  
Cellular Proliferation ◽  
The Elderly ◽  
Yolk Sac ◽  
Hematopoietic Stem ◽  
Macrophage Population ◽  
Adult Kidney ◽  
Macrophage Populations ◽  
Injury And Repair ◽  
Specialized Population

Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, angiogenesis, and tissue remodeling. Recent reports highlight differential roles for ontogenically distinct renal macrophage populations in disease. However, little is known about how these populations change over time in normal, uninjured kidneys. Prior reports demonstrated a high proportion of HSC-derived macrophages in the young adult kidney. Unexpectedly, using genetic fate-mapping and parabiosis studies, we found that yolk-sac-derived macrophages progressively expand in number with age and become a major contributor to the renal macrophage population in older mice. This chronological shift in macrophage composition involves local cellular proliferation and recruitment from circulating progenitors and may contribute to the distinct immune responses, limited reparative capacity, and increased disease susceptibility of kidneys in the elderly population.

Deletion of Myeloid Interferon Regulatory Factor 4 (Irf4) in Mouse Model Protects against Kidney Fibrosis after Ischemic Injury by Decreased Macrophage Recruitment and Activation

2021 ◽  
pp. ASN.2020071010
Author(s):  
Kensuke Sasaki ◽  
Andrew S. Terker ◽  
Yu Pan ◽  
Zhilian Li ◽  
Shirong Cao ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Macrophage Polarization ◽  
Kidney Injury ◽  
Significant Inhibition ◽  
Macrophage Infiltration ◽  
Wild Type ◽  
Regulatory Factor ◽  
Macrophage Cell ◽  
Kidney Fibrosis ◽  
M2 Phenotype

BackgroundAKI is characterized by abrupt and reversible kidney dysfunction, and incomplete recovery leads to chronic kidney injury. Previous studies by us and others have indicated that macrophage infiltration and polarization play key roles in recovery from AKI. The role in AKI recovery played by IFN regulatory factor 4 (IRF4), a mediator of polarization of macrophages to the M2 phenotype, is unclear.MethodsWe used mice with myeloid or macrophage cell–specific deletion of Irf4 (MΦ Irf4−/−) to evaluate Irf4’s role in renal macrophage polarization and development of fibrosis after severe AKI.ResultsSurprisingly, although macrophage Irf4 deletion had a minimal effect on early renal functional recovery from AKI, it resulted in decreased renal fibrosis 4 weeks after severe AKI, in association with less-activated macrophages. Macrophage Irf4 deletion also protected against renal fibrosis in unilateral ureteral obstruction. Bone marrow–derived monocytes (BMDMs) from MΦ Irf4−/− mice had diminished chemotactic responses to macrophage chemoattractants, with decreased activation of AKT and PI3 kinase and increased PTEN expression. PI3K and AKT inhibitors markedly decreased chemotaxis in wild-type BMDMs, and in a cultured macrophage cell line. There was significant inhibition of homing of labeled Irf4−/− BMDMs to postischemic kidneys. Renal macrophage infiltration in response to AKI was markedly decreased in MΦ Irf4−/− mice or in wild-type mice with inhibition of AKT activity.ConclusionsDeletion of Irf4 from myeloid cells protected against development of tubulointerstitial fibrosis after severe ischemic renal injury in mice, due primarily to inhibition of AKT-mediated monocyte recruitment to the injured kidney and reduced activation and subsequent polarization into a profibrotic M2 phenotype.

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