Mechanisms of Positive Effects of Transplantation of Human Placental Mesenchymal Stem Cells on Recovery of Rats after Experimental Ischemic Stroke

2009 ◽  
Vol 148 (6) ◽  
pp. 862-868 ◽  
Author(s):  
K. N. Yarygin ◽  
I. V. Kholodenko ◽  
A. A. Konieva ◽  
V. V. Burunova ◽  
R. T. Tairova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Positive Effects ◽  
Placental Mesenchymal Stem Cells

Abstract TP102: Human Placental Mesenchymal Stem Cells Derived Exosome-Angiotensin Converting Enzyme-2 Dependent Protection in Ischemic Stroke Injury

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mansoureh Barzegar ◽  
Yuping Wang ◽  
Jungmi W. Yun ◽  
Oleg Chernyshev ◽  
Roger Kelley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Flow ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Angiotensin Converting Enzyme ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Placental Mesenchymal Stem Cells

Following thrombolytic therapy for stroke, ischemia/reperfusion (I/R) mediated inflammation often disrupts the blood brain barrier (BBB). This can enhance expression of endothelial adhesion markers and perturb normal blood flow regulation. Proposed benefits of stem cell therapy (SCT) in stroke, besides long-term trans-differentiation into neural cells, include secretion of protective factors, which partly depends on exosomes released by stem cells. We evaluated human placenta mesenchymal stem cells (hPMSC) as potential ameliorative SCT in an acute ischemic stroke model. We hypothesize that hPMSC would achieve site-specific suppression of post-ischemic immune cell transmigration, preservation of the BBB and maintenance of blood flow via ‘paracrine’ signaling pathways in acute stroke injury.We found that intraperitoneal (IP) administration of hPMSC at the time of reperfusion, using the middle cerebral artery occlusion (MCAO)/reperfusion model, produced significant protection ( p =0.0001) of the ipsilateral hemisphere. We also demonstrated that hPMSC-treated MCAO mice exhibited significantly greater neurological recovery ( p <0.0001) compared to untreated MCAO, an effect which was accompanied by significant restoration of blood flow ( p <0.01) to the MCAO-stressed brains. Using Evans Blue dye assay, we also observed significant ( p =0.004) improvement of BBB integrity in ipsilateral hemispheres of hPMSC-treated mice vs MCAO controls. Furthermore, we determined that hPMSC-derived exosomes contribute to paracrine based protection of hPMSC in MCAO model. Importantly, we found that hPMSC/exosome protection is mediated partly by the function of angiotensin converting enzyme 2 (ACE2). To evaluate the contribution of ACE2 in protection of the brain after ischemic stroke, we first demonstrated that hPMSC and their exosomes express ACE2. Second, mice injected with hPMSC which had been pre-treated with the specific ACE2 inhibitor (10μM) MLN-4760, showed tissue injury and neurological behavior similar to that seen in untreated MCAO.We conclude that pleiotropic factors associated with hPMSC administration can have a favorable impact on blood flow, BBB integrity potentially alleviating the detrimental effects of ischemic stroke.

High Glucose Affects the Cytotoxic Potential of Rapamycin, Metformin and Hydrogen Peroxide in Cultured Human Mesenchymal Stem Cells

2019 ◽  
Vol 19 (9) ◽  
pp. 688-698 ◽  
Author(s):  
Azam Roohi ◽  
Mahin Nikougoftar ◽  
Hamed Montazeri ◽  
Shadisadat Navabi ◽  
Fazel Shokri ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hydrogen Peroxide ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Viability ◽  
High Glucose ◽  
Cell Cycle Distribution ◽  
Efficient Treatment ◽  
Chronic Hyperglycemia ◽  
Placental Mesenchymal Stem Cells

Background: Oxidative stress and chronic hyperglycemia are two major side effects of type 2 diabetes affecting all cell types including mesenchymal stem cells (MSCs). As a cell therapy choice, understanding the behavior of MSCs will provide crucial information for efficient treatment. Methods: Placental mesenchymal stem cells were treated with various concentrations of glucose, metformin, rapamycin, and hydrogen peroxide to monitor their viability and cell cycle distribution. Cellular viability was examined via the MTT assay. Cell cycle distribution was studied by propidium iodide staining and apoptosis was determined using Annexin Vpropidium iodide staining and flow cytometry. Involvement of potential signaling pathways was evaluated by Western blotting for activation of Akt, P70S6K, and AMPK. Results: The results indicated that high glucose augmented cell viability and reduced metformin toxic potential. However, the hydrogen peroxide and rapamycin toxicities were exacerbated. Conclusion: Our findings suggest that high glucose concentration has a major effect on placental mesenchymal stem cell viability in the presence of rapamycin, metformin and hydrogen peroxide in culture.

Extracellular vesicles from three dimensional culture of human placental mesenchymal stem cells ameliorated renal ischemia/reperfusion injury

2021 ◽  
pp. 039139882098680
Author(s):  
Xuefeng Zhang ◽  
Nan Wang ◽  
Yuhua Huang ◽  
Yan Li ◽  
Gang Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Expression Profiles ◽  
Ischemia Reperfusion ◽  
Three Dimensional ◽  
3D Culture ◽  
Placental Mesenchymal Stem Cells ◽  
2D And 3D

Background: Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). Methods: The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. Results: The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. Conclusion: The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.

scholarly journals Efficacy of topical and systemic transplantation of mesenchymal stem cells in a rat model of diabetic ischemic wounds

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianxin Yan ◽  
Jiaji Liang ◽  
Yingxuan Cao ◽  
Mariya M. El Akkawi ◽  
Xuan Liao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Chronic Wounds ◽  
Blood Perfusion ◽  
Systemic Administration ◽  
Critical Parameters ◽  
Administration Routes ◽  
Positive Effects ◽  
Systemic Treatments

Abstract Background Mesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms. Method A diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis. Result Both topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway. Conclusions The results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.

scholarly journals Mesenchymal Stem Cells Overexpressing Interleukin-10 Promote Neuroprotection in Experimental Acute Ischemic Stroke

2017 ◽  
Vol 6 ◽  
pp. 102-111 ◽  
Author(s):  
Masataka Nakajima ◽  
Chikako Nito ◽  
Kota Sowa ◽  
Satoshi Suda ◽  
Yasuhiro Nishiyama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Interleukin 10

scholarly journals Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuejiao Li ◽  
Yankai Dong ◽  
Ye Ran ◽  
Yanan Zhang ◽  
Boyao Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Proinflammatory Cytokines ◽  
Infarct Volume ◽  
Brain Lesion ◽  
Three Dimensional ◽  
Artery Occlusion ◽  
Rna Seq ◽  
The Brain

Abstract Background We show previously that three-dimensional (3D) spheroid cultured mesenchymal stem cells (MSCs) exhibit reduced cell size thus devoid of lung entrapment following intravenous (IV) infusion. In this study, we determined the therapeutic effect of 3D-cultured MSCs on ischemic stroke and investigated the mechanisms involved. Methods Rats underwent middle cerebral artery occlusion (MCAO) and reperfusion. 1 × 106 of 3D- or 2D-cultured MSCs, which were pre-labeled with GFP, were injected through the tail vain three and seven days after MCAO. Two days after infusion, MSC engraftment into the ischemic brain tissues was assessed by histological analysis for GFP-expressing cells, and infarct volume was determined by MRI. Microglia in the lesion were sorted and subjected to gene expressional analysis by RNA-seq. Results We found that infusion of 3D-cultured MSCs significantly reduced the infarct volume of the brain with increased engraftment of the cells into the ischemic tissue, compared to 2D-cultured MSCs. Accordingly, in the brain lesion of 3D MSC-treated animals, there were significantly reduced numbers of amoeboid microglia and decreased levels of proinflammatory cytokines, indicating attenuated activation of the microglia. RNA-seq of microglia derived from the lesions suggested that 3D-cultured MSCs decreased the response of microglia to the ischemic insult. Interestingly, we observed a decreased expression of mincle, a damage-associated molecular patterns (DAMPs) receptor, which induces the production of proinflammatory cytokines, suggestive of a potential mechanism in 3D MSC-mediated enhanced repair to ischemic stroke. Conclusions Our data indicate that 3D-cultured MSCs exhibit enhanced repair to ischemic stroke, probably through a suppression to ischemia-induced microglial activation.

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