scholarly journals Immunomodulatory Properties of Mesenchymal Stromal Cells Can Vary in Genetically Modified Rats

2021 ◽  
Vol 22 (3) ◽  
pp. 1181
Author(s):  
Natalie Vallant ◽  
Bynvant Sandhu ◽  
Karim Hamaoui ◽  
Maria Prendecki ◽  
Charles Pusey ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Fluorescent Protein ◽  
Ischemia Reperfusion Injury ◽  
Genetically Modified ◽  
Ischemia Reperfusion ◽  
Expression Patterns ◽  
Solid Organ Transplantation ◽  
Solid Organ

Mesenchymal Stromal Cells (MSC) have been shown to exhibit immuno-modulatory and regenerative properties at sites of inflammation. In solid organ transplantation (SOT), administration of MSCs might lead to an alleviation of ischemia-reperfusion injury and a reduction of rejection episodes. Previous reports have suggested ‘MSC-preconditioning’ of macrophages to be partly responsible for the beneficial effects. Whether this results from direct cell-cell interactions (e.g., MSC trans-differentiation at sites of damage), or from paracrine mechanisms, remains unclear. Immunosuppressive capacities of MSCs from donors of different age and from genetically modified donor animals, often used for in-vivo experiments, have so far not been investigated. We conducted an in vitro study to compare paracrine effects of supernatants from MSCs extracted from young and old wild-type Wystar-Kyoto rats (WKY-wt), as well as young and old WKY donor rats positive for the expression of green fluorescent protein (WKY-GFP), on bone marrow derived macrophages (BMDM). Expression levels of Mannose receptor 1 (Mrc-1), Tumor necrosis factor α (TNFα), inducible NO synthase (iNos) and Interleukin-10 (IL-10) in BMDMs after treatment with different MSC supernatants were compared by performance of quantitative PCR. We observed different expression patterns of inflammatory markers within BMDMs, depending on age and genotype of origin for MSC supernatants. This must be taken into consideration for preclinical and clinical studies, for which MSCs will be used to treat transplant patients, aiming to mitigate inflammatory and allo-responses.

scholarly journals The Functions of Clusterin Expression in Renal Mesenchymal Stromal Cells: Regulation of Cell Proliferation and Macrophage Activation

2021 ◽  
Author(s):  
xiaodong weng ◽  
Jing Li ◽  
Qiunong Guan ◽  
Haimei Zhao ◽  
Zihuan Wang ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Tissue ◽  
Renal Protection ◽  
Phagocytic Capacity ◽  
Induced Apoptosis ◽  
Clusterin Expression

Abstract BackgroundThe expression of clusterin (CLU) in mice increases resistance to renal ischemia-reperfusion injury and promotes renal tissue repair. However, the mechanisms underlying of the renal protection of CLU remain largely unknown. Mesenchymal stromal cells (MSCs), found in different compartments of the kidney, may contribute to kidney cell turnover and injury repair. This study investigated the in vitro functions of CLU in kidney mesenchymal stromal cells (KMSCs). MethodsKMSCs were isolated by digestion of kidney tissues with collagenase type 1 and growth in plastic culture plates. Cell surface markers, apoptosis and phagocytosis were determined by flow cytometry, and CLU protein by Western blot. ResultsKMSCs isolated from both wild type (WT) and CLU knockout (KO) mice positively expressed CD133, Sca-1, CD44, and CD117, and negatively of CD34, CD45, CD163, CD41, CD276, CD138 and CD79a. There was no difference in trilineage differentiation to chondrocytes, adipocytes and osteocytes between WT and KO KMSCs. CLU protein was expressed in and secreted by WT KMSCs, and it was up-regulated in response to hypoxia, but the degrees of hypoxia-induced apoptosis in WT KMSCs were not significantly different from those in KO KMSCs. The WT KMSCs proliferated faster than KO KMSCs in cultures. Furthermore, the incubation of macrophages with CLU-containing culture medium from WT KMSCs increased the CD206 expression in the macrophages and their phagocytic capacity. ConclusionOur data for the first time demonstrate the functions of CLU in the promotion of KMSCs proliferation, and may be required for KMSCs-regulated macrophage M2 polarization and phagocytic activity.

scholarly journals The Functions of Clusterin Expression in Renal Mesenchymal Stromal Cells: Regulation of Cell Proliferation and Macrophage Activation

2021 ◽  
Author(s):  
xiaodong weng ◽  
Jing Li ◽  
Qiunong Guan ◽  
Haimei Zhao ◽  
Zihuan Wang ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Tissue ◽  
Renal Protection ◽  
Phagocytic Capacity ◽  
Induced Apoptosis ◽  
Clusterin Expression

Abstract The expression of clusterin (CLU) in mice increases resistance to renal ischemia-reperfusion injury and promotes renal tissue repair. However, the mechanisms underlying of the renal protection of CLU remain largely unknown. Mesenchymal stromal cells (MSCs), found in different compartments of the kidney, may contribute to kidney cell turnover and injury repair. This study investigated the in vitro functions of CLU in kidney mesenchymal stromal cells (KMSCs). KMSCs were isolated by digestion of kidney tissues with collagenase type 1 and growth in plastic culture plates. Cell surface markers, apoptosis and phagocytosis were determined by flow cytometry, and CLU protein by Western blot. Here, we showed that KMSCs isolated from both wild type (WT) and CLU knockout (KO) mice positively expressed CD133, Sca-1, CD44, and CD117, and negatively of CD34, CD45, CD163, CD41, CD276, CD138 and CD79a. There was no difference in trilineage differentiation to chondrocytes, adipocytes and osteocytes between WT and KO KMSCs. CLU protein was expressed in and secreted by WT KMSCs, and it was up-regulated in response to hypoxia. However, lack of CLU expression did not negatively affect hypoxia-induced apoptosis in cultured KMSCs. The WT KMSCs proliferated faster than KO KMSCs in cultures. Furthermore, the incubation of macrophages with CLU-containing culture medium from WT KMSCs increased the CD206 expression in the macrophages and their phagocytic capacity. In conclusion, our data for the first time demonstrate the functions of CLU in the promotion of KMSCs proliferation, and may be required for KMSCs-regulated macrophage M2 polarization and phagocytic activity.

scholarly journals Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Di Gu ◽  
Xiangyu Zou ◽  
Guanqun Ju ◽  
Guangyuan Zhang ◽  
Erdun Bao ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Apoptosis Pathway ◽  
Acute Renal Ischemia

Background. The immoderation of mitochondrial fission is one of the main contributors in ischemia reperfusion injury (IRI) and mesenchymal stromal cells (MSCs) derived extracellular vesicles have been regarded as a potential therapy method. Here, we hypothesized that extracellular vesicles (EVs) derived from human Wharton Jelly mesenchymal stromal cells (hWJMSCs) ameliorate acute renal IRI by inhibiting mitochondrial fission through miR-30b/c/d.Methods. EVs isolated from the condition medium of MCS were injected intravenously in rats immediately after monolateral nephrectomy and renal pedicle occlusion for 45 minutes. Animals were sacrificed at 24 h after reperfusion and samples were collected. MitoTracker Red staining was used to see the morphology of the mitochondria. The expression of DRP1 was measured by western blot. miR-30 in EVs and rat tubular epithelial cells was assessed by qRT-PCR. Apoptosis pathway was identified by immunostaining.Results. We found that the expression of miR-30 in injured kidney tissues was declined and mitochondrial dynamics turned to fission. But they were both restored in EVs group in parallel with reduced cell apoptosis. What is more, when the miR-30 antagomirs were used to reduce the miRNA levels, all the related effects of EVs reduced remarkably.Conclusion. A single administration of hWJMSC-EVs could protect the kidney from IRI by inhibition of mitochondrial fission via miR-30.

scholarly journals BMP Antagonists Secreted by Mesenchymal Stromal Cells Improve Colonic Organoid Formation: Application for the Treatment of Radiation-induced Injury

2020 ◽  
Vol 29 ◽  
pp. 096368972092968
Author(s):  
Lara Moussa ◽  
Alexia Lapière ◽  
Claire Squiban ◽  
Christelle Demarquay ◽  
Fabien Milliat ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Radiation Effects ◽  
Fluorescent Protein ◽  
Therapeutic Benefit ◽  
Therapeutic Effects ◽  
Gastrointestinal Complications

Radiation therapy is crucial in the therapeutic arsenal to cure cancers; however, non-neoplastic tissues around an abdominopelvic tumor can be damaged by ionizing radiation. In particular, the radio-induced death of highly proliferative stem/progenitor cells of the colonic mucosa could induce severe ulcers. The importance of sequelae for patients with gastrointestinal complications after radiotherapy and the absence of satisfactory management has opened the field to the testing of innovative treatments. The aim of this study was to use adult epithelial cells from the colon, to reduce colonic injuries in an animal model reproducing radiation damage observed in patients. We demonstrated that transplanted in vitro-amplified epithelial cells from colonic organoids (ECO) of C57/Bl6 mice expressing green fluorescent protein implant, proliferate, and differentiate in irradiated mucosa and reduce ulcer size. To improve the therapeutic benefit of ECO-based treatment with clinical translatability, we performed co-injection of ECO with mesenchymal stromal cells (MSCs), cells involved in niche function and widely used in clinical trials. We observed in vivo an improvement of the therapeutic benefit and in vitro analysis highlighted that co-culture of MSCs with ECO increases the number, proliferation, and size of colonic organoids. We also demonstrated, using gene expression analysis and siRNA inhibition, the involvement of bone morphogenetic protein antagonists in MSC-induced organoid formation. This study provides evidence of the potential of ECO to limit late radiation effects on the colon and opens perspectives on combined strategies to improve their amplification abilities and therapeutic effects.

Mesenchymal Stromal Cells in Solid Organ Transplantation

2020 ◽  
Vol 104 (5) ◽  
pp. 923-936 ◽  
Author(s):  
Morgan Vandermeulen ◽  
Pauline Erpicum ◽  
Laurent Weekers ◽  
Alexandra Briquet ◽  
Chantal Lechanteur ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Solid Organ Transplantation ◽  
Solid Organ

scholarly journals Reparative Effect of Mesenchymal Stromal Cells on Endothelial Cells after Hypoxic and Inflammatory Injury

2020 ◽  
Author(s):  
Jesus Maria Sierra-Parraga ◽  
Ana Merino ◽  
Marco Eijken ◽  
Henri Leuvenink ◽  
Rutger J. Ploeg ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Umbilical Vein ◽  
Ischemia Reperfusion ◽  
Therapeutic Effects ◽  
Physical Interaction ◽  
Paracrine Interaction

Abstract Background The renal endothelium is a prime target for ischemia reperfusion injury (IRI) during donation and transplantation procedures. Mesenchymal stromal cells (MSC) have been shown to ameliorate kidney function after IRI. However, whether this involves repair of the endothelium is not clear. Therefore, our objective is to study potential regenerative effects of MSC on injured endothelial cells and to identify the molecular mechanisms involved. Methods Human umbilical vein endothelial cells (HUVEC) were submitted to hypoxia and reoxygenation and TNF-a treatment. To determine whether physical interaction or soluble factors released by MSC were responsible for the potential regenerative effects of MSC on endothelial cells, dose-response experiments were performed in co-culture and transwell conditions and with secretome deficient MSC. Results MSC showed increased migration and adhesion to injured HUVEC, mediated by CD29 and CD44 on the MSC membrane. MSC decreased membrane injury marker expression, oxidative stress levels and monolayer permeability of injured HUVEC, which was observed only when allowing both physical and paracrine interaction between MSC and HUVEC. Furthermore, viable MSC in direct contact with injured HUVEC improved wound healing capacity by 45% and completely restored their angiogenic capacity. In addition, MSC exhibited an increased ability to migrate through an injured HUVEC monolayer compared to non-injured HUVEC in vitro. Conclusions These results show that MSC have regenerative effects on injured HUVEC via a mechanism which requires both physical and paracrine interaction. The identification of specific effector molecules involved in MSC-HUVEC interaction will allow targeted modification of MSC to apply and enhance the therapeutic effects of MSC in IRI.

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