Overexpression of Heme Oxygenase-1 in Mesenchymal Stem Cells Augments Their Protection on Retinal Cells In Vitro and Attenuates Retinal Ischemia/Reperfusion Injury In Vivo against Oxidative Stress

Li, Li; Du, Gaiping; Wang, DaJiang; Zhou, Jin; Jiang, Guomin; Jiang, Hua

doi:10.1155/2017/4985323

Cited by 20 publications

(19 citation statements)

References 45 publications

(52 reference statements)

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“…102,103 The preservation of ELECTRICAL ENRICHMENT OF HMSCS stemness remains one of the priorities in many in vitro investigations with the assumption that a more stem-like state correlates with better therapeutic immunomodulation. We found that MSC-DC H had elevated mRNA expression of HO-1, a rate-limiting enzyme in heme metabolism, with anti-inflammatory, antioxidative, and antiapoptotic functions, 104,105 as well as pleiotropic cytokine IL-6, which is heavily involved in the immunomodulatory function of MSCs. However, after 24 h of culture of EE-hMSCs, we observed a shift toward greater expression of HO-1 and IL-6 in MSC-DC L .…”

Section: Discussionmentioning

confidence: 88%

Assessment of Enrichment of Human Mesenchymal Stem Cells Based on Plasma and Mitochondrial Membrane Potentials

et al. 2020

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Background: Human mesenchymal stem cells (hMSCs) are utilized preclinically and clinically as a candidate cell therapy for a wide range of inflammatory and degenerative diseases. Despite promising results in early clinical trials, consistent outcomes with hMSC-based therapies have proven elusive in many of these applications. In this work, we attempt to address this limitation through the design of a stem cell therapy to enrich hMSCs for desired electrical and ionic properties with enhanced stemness and immunomodulatory/regenerative capacity. Materials and Methods: In this study, we sought to develop initial protocols to achieve electrically enriched hMSCs (EE-hMSCs) with distinct electrical states and assess the potential relationship with respect to hMSC state and function. We sorted hMSCs based on fluorescence intensity of tetramethylrhodamine ethyl ester (TMRE) and investigated phenotypic differences between the sorted populations. Results: Subpopulations of EE-hMSCs exhibit differential expression of genes associated with senescence, stemness, immunomodulation, and autophagy. EE-hMSCs with low levels of TMRE, indicative of depolarized membrane potential, have reduced mRNA expression of senescence-associated markers, and increased mRNA expression of autophagy and immunomodulatory markers relative to EE-hMSCs with high levels of TMRE (hyperpolarized). Conclusions: This work suggests that the utilization of EE-hMSCs may provide a novel strategy for cell therapies, enabling live cell enrichment for distinct phenotypes that can be exploited for different therapeutic outcomes.

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Section: Discussionmentioning

confidence: 88%

Assessment of Enrichment of Human Mesenchymal Stem Cells Based on Plasma and Mitochondrial Membrane Potentials

et al. 2020

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“…Similarly, overexpression of proteasome subunit beta 5 (PSMB5) maintains the differentiation capacity of late‐passage MSCs, even under exposure to H 2 O 2 , and overexpression of heme oxygenase 1 in MSCs significantly attenuates H 2 O 2 ‐induced injury of retinal ganglion cells by decreasing levels of cellular ROS and proapoptotic proteins. Thus, modified MSCs are highly effective at attenuating retinal I/R injury by maintaining structural thickness and decreasing apoptosis . In addition to general virus‐mediated overexpression of critical genes, microRNAs (miRNAs) and small molecules contribute to the regulation of MSC activities by modulating ROS levels.…”

Section: Strategies To Control Ros Levels For Msc Fates In Vitro and mentioning

confidence: 99%

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

Zhao

Peng

et al. 2018

J Cellular Molecular Medi

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Mesenchymal stem cells (MSCs) are broadly used in cell‐based regenerative medicine because of their self‐renewal and multilineage potencies in vitro and in vivo. To ensure sufficient amounts of MSCs for therapeutic purposes, cells are generally cultured in vitro for long‐term expansion or specific terminal differentiation until cell transplantation. Although physiologically up‐regulated reactive oxygen species (ROS) production is essential for maintenance of stem cell activities, abnormally high levels of ROS can harm MSCs both in vitro and in vivo. Overall, additional elucidation of the mechanisms by which physiological and pathological ROS are generated is necessary to better direct MSC fates and improve their therapeutic effects by controlling external ROS levels. In this review, we focus on the currently revealed ROS generation mechanisms and the regulatory routes for controlling their rates of proliferation, survival, senescence, apoptosis, and differentiation. A promising strategy in future regenerative medicine involves regulating ROS generation via various means to augment the therapeutic efficacy of MSCs, thus improving the prognosis of patients with terminal diseases.

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“…34,52 Our TUNEL results suggest that CoPP is sufficient to alleviate the photoreceptor apoptosis in MNU-administered mice. A previous study 53 also has shown that HO-1 overexpression inhibits RGC apoptosis in ischemic retinas. CoPP treatment can enhance Bcl-2 expression and adjust the Bcl/Bax ratio toward a net ''antiapoptotic'' effect.…”

Section: Discussionmentioning

confidence: 78%

CoPP-Induced-Induced HO-1 Overexpression Alleviates Photoreceptor Degeneration With Rapid Dynamics: A Therapeutic Molecular Against Retinopathy

Tao

Cai

Zhou

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Retinitis pigmentosa (RP) causes progressive photoreceptor degeneration in the retina. The N-methyl-N-nitrosourea (MNU)-administered mouse is used as a chemically induced RP model with rapid progression rate. This study was designed to study heme oxygenase-1 (HO-1) expression in the MNU-administered mice, and to explore the therapeutic effects of cobalt protoporphyrin (CoPP). METHODS. The HO-1 expression in the retina of MNU-administered mice was analyzed. CoPP was injected intravenously into the MNU-administered mice. Subsequently, the CoPP-treated mice were subjected to functional and morphologic examinations. RESULTS. HO-1 was involved in the MNU-induced photoreceptor degeneration. CoPP treatment enhanced retinal HO-1 expression in the MNU-administered mice. Electroretinogram (ERG) examination and behavioral tests showed that CoPP treatment improved the retinal responsiveness of MNU-administered mice. Histologic analysis and optical coherence tomography (OCT) examination showed that retinal architecture of the CoPP-treated mice was more intact than that of the MNUþvehicle group. Cone photoreceptors in the MNUadministered mice were rescued efficiently by CoPP treatment. Furthermore, multielectrode array (MEA) recording showed that CoPP treatment mitigated the spontaneous firing response, enhanced the light-induced firing response, and preserved the basic configurations of visual signal pathway in the MNU-administered mice. Mechanism studies suggested that CoPP afforded these therapeutic effects by modulating the apoptosis cascades and alleviating the oxidative stress in degenerative retinas. CONCLUSIONS. CoPP alleviated photoreceptor degeneration and rectified the signaling abnormities in MNU-administered mice. CoPP may serve as a potential medication against degenerative retinopathy.

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Overexpression of Heme Oxygenase-1 in Mesenchymal Stem Cells Augments Their Protection on Retinal Cells In Vitro and Attenuates Retinal Ischemia/Reperfusion Injury In Vivo against Oxidative Stress

Cited by 20 publications

References 45 publications

Assessment of Enrichment of Human Mesenchymal Stem Cells Based on Plasma and Mitochondrial Membrane Potentials

Assessment of Enrichment of Human Mesenchymal Stem Cells Based on Plasma and Mitochondrial Membrane Potentials

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

CoPP-Induced-Induced HO-1 Overexpression Alleviates Photoreceptor Degeneration With Rapid Dynamics: A Therapeutic Molecular Against Retinopathy

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