scholarly journals Extracellular Vesicles Derived from Induced Pluripotent Stem Cells Promote Renoprotection in Acute Kidney Injury Model

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 453 ◽  
Author(s):  
Federica Collino ◽  
Jarlene A. Lopes ◽  
Marta Tapparo ◽  
Giovane G. Tortelote ◽  
Taís H. Kasai-Brunswick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Induced Pluripotent Stem Cells ◽  
Extracellular Vesicles ◽  
Pluripotent Stem Cells ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Gene Array ◽  
Wide Range ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSC) have been the focus of several studies due to their wide range of application, including in cellular therapy. The use of iPSC in regenerative medicine is limited by their tumorigenic potential. Extracellular vesicles (EV) derived from stem cells have been shown to support renal recovery after injury. However, no investigation has explored the potential of iPSC-EV in the treatment of kidney diseases. To evaluate this potential, we submitted renal tubule cells to hypoxia-reoxygenation injury, and we analyzed cell death rate and changes in functional mitochondria mass. An in vivo model of ischemia-reperfusion injury was used to evaluate morphological and functional alterations. Gene array profile was applied to investigate the mechanism involved in iPSC-EV effects. In addition, EV derived from adipose mesenchymal cells (ASC-EV) were also used to compare the potential of iPSC-EV in support of tissue recovery. The results showed that iPSC-EV were capable of reducing cell death and inflammatory response with similar efficacy than ASC-EV. Moreover, iPSC-EV protected functional mitochondria and regulated several genes associated with oxidative stress. Taken together, these results show that iPSC can be an alternative source of EV in the treatment of different aspects of kidney disease.

scholarly journals Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Luciana Isaja ◽  
Sofía Mucci ◽  
Jonathan Vera ◽  
María Soledad Rodríguez-Varela ◽  
Mariela Marazita ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Cell Viability ◽  
Pluripotent Stem Cells ◽  
Chromatin Condensation ◽  
Human Pluripotent Stem Cells ◽  
Chemical Hypoxia ◽  
Wide Range ◽  
Independent Mechanism ◽  
Induced Pluripotent

AbstractHuman embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are self-renewing human pluripotent stem cells (hPSCs) that can differentiate to a wide range of specialized cells. Notably, hPSCs enhance their undifferentiated state and self-renewal properties in hypoxia (5% O2). Although thoroughly analyzed, hypoxia implication in hPSCs death is not fully determined. In order to evaluate the effect of chemically mimicked hypoxia on hPSCs cell survival, we analyzed changes in cell viability and several aspects of apoptosis triggered by CoCl2 and dimethyloxalylglycine (DMOG). Mitochondrial function assays revealed a decrease in cell viability at 24 h post-treatments. Moreover, we detected chromatin condensation, DNA fragmentation and CASPASE-9 and 3 cleavages. In this context, we observed that P53, BNIP-3, and NOXA protein expression levels were significantly up-regulated at different time points upon chemical hypoxia induction. However, only siRNA-mediated downregulation of NOXA but not HIF-1α, HIF-2α, BNIP-3, and P53 did significantly affect the extent of cell death triggered by CoCl2 and DMOG in hPSCs. In conclusion, chemically mimicked hypoxia induces hPSCs cell death by a NOXA-mediated HIF-1α and HIF-2α independent mechanism.

scholarly journals Induced Pluripotent Stem Cells Attenuate Acute Lung Injury Induced by Ischemia Reperfusion via Suppressing the High Mobility Group Box-1

Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582096934
Author(s):  
Yijun Li ◽  
Shun Wang ◽  
Jinbo Liu ◽  
Xingyu Li ◽  
Meng Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Lung Injury ◽  
Endothelial Cell ◽  
Lung Injury ◽  
Induced Pluripotent Stem Cells ◽  
Inflammatory Cytokines ◽  
Pluripotent Stem Cells ◽  
Ischemia Reperfusion ◽  
High Mobility ◽  
Induced Pluripotent

Pulmonary endothelial cell injury is a hallmark of acute lung injury. High-mobility group box 1 (HMGB1) can modulate the inflammatory response via endothelial cell activation and release of inflammatory molecules. Thus, we tested whether induced pluripotent stem cells (iPSCs) can alleviate ischemia/reperfusion (I/R) induced lung injury, and, if so, whether HMGB1 mediates the effect in a male C57BL/6 mouse model. Intravenously injected iPSCs into mice 2 h after I/R showed a significant attenuation of lung injury (assessed by lung mechanics, edema, and histology) 24 h after reperfusion (compared with controls), along with decreases in HMGB1, phosphorylated nuclear factor-κB, inflammatory cytokines [interleukin (IL)1β, IL6 and tumor necrosis factor-α], and the activation of endothelial cells. Furthermore, these effects of iPSCs can be mimicked by blocking HMGB1 with an inhibitor in vivo and in vitro. We conclude that iPSCs can be a potential therapy for I/R-induced lung injury. These cells may exert therapeutic effects through blocking HMGB1 and inflammatory cytokines.

scholarly journals The Progress of Induced Pluripotent Stem Cells as Models of Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Ji-feng Kang ◽  
Bei-sha Tang ◽  
Ji-feng Guo
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Pharmacological Study ◽  
Somatic Cells ◽  
Wide Range ◽  
Induced Pluripotent

In recent years, induced pluripotent stem cells (iPSCs) were widely used for investigating the mechanisms of Parkinson’s disease (PD). Somatic cells from patients withSNCA(α-synuclein),LRRK2(leucine-rich repeat kinase 2),PINK1(PTEN induced putative kinase 1),Parkinmutations, and at-risk individuals carryingGBA(β-glucocerebrosidase) mutations have been successfully induced to iPSCs and subsequently differentiated into dopaminergic (DA) neurons. Importantly, some PD-related cell phenotypes, includingα-synuclein aggregation, mitophagy, damaged mitochondrial DNA, and mitochondrial dysfunction, have been described in these iPSCs models, which further investigated the pathogenesis of PD. In 2007, Takahashi et al. and Vodyanik et al. generated iPSCs from human somatic cells for the first time. Since then, patients derived iPSCs were applied for disease modeling, drug discovery and screening, autologous cell replacement therapy, and other biological applications. iPSC research has now become a hot topic in a wide range of fields. This review summarizes the recent progress of PD patients derived iPSC models in pathogenic mechanism investigation and potential clinical applications, especially their promising strategy in pharmacological study and DA neurons transplantation therapy. However, the challenges of iPSC transplantation still exist, and it has a long way to go before it can be used in clinical application.

scholarly journals Using induced pluripotent stem cells to understand retinal ciliopathy disease mechanisms and develop therapies

2016 ◽  
Vol 44 (5) ◽  
pp. 1245-1251 ◽  
Author(s):  
David A. Parfitt ◽  
Amelia Lane ◽  
Conor Ramsden ◽  
Katarina Jovanovic ◽  
Peter J. Coffey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Retinal Degeneration ◽  
Pluripotent Stem Cells ◽  
Photoreceptor Cells ◽  
Cell Types ◽  
Disease Mechanisms ◽  
Wide Range ◽  
Induced Pluripotent

The photoreceptor cells in the retina have a highly specialised sensory cilium, the outer segment (OS), which is important for detecting light. Mutations in cilia-related genes often result in retinal degeneration. The ability to reprogramme human cells into induced pluripotent stem cells and then differentiate them into a wide range of different cell types has revolutionised our ability to study human disease. To date, however, the challenge of producing fully differentiated photoreceptors in vitro has limited the application of this technology in studying retinal degeneration. In this review, we will discuss recent advances in stem cell technology and photoreceptor differentiation. In particular, the development of photoreceptors with rudimentary OS that can be used to understand disease mechanisms and as an important model to test potential new therapies for inherited retinal ciliopathies.

scholarly journals Exacerbation of Oxidative Stress-Induced Cell Death and Differentiation in Induced Pluripotent Stem Cells Lacking Heme Oxygenase-1

2012 ◽  
Vol 21 (10) ◽  
pp. 1675-1687 ◽  
Author(s):  
Chen-Yu Lin ◽  
Chiu-Ying Peng ◽  
Tzu-Ting Huang ◽  
Meng-Ling Wu ◽  
Yan-Liang Lai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cell Death ◽  
Induced Pluripotent Stem Cells ◽  
Heme Oxygenase ◽  
Pluripotent Stem Cells ◽  
Heme Oxygenase 1 ◽  
Induced Pluripotent

Induced pluripotent stem cells alleviate lung injury from mesenteric ischemia-reperfusion

2015 ◽  
Vol 79 (4) ◽  
pp. 592-601 ◽  
Author(s):  
Chorng-Kuang How ◽  
Sen-Kuang Hou ◽  
Luen-Kui Chen ◽  
Cheng-Ming Yang ◽  
Hsien-Hao Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Lung Injury ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion ◽  
Induced Pluripotent
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