Therapeutic effect against retinal neovascularization in a mouse model of oxygen-induced retinopathy: bone marrow-derived mesenchymal stem cells versus Conbercept

Xu, Wei; Cheng, Weiqiang; Cui, Xiao-Yuan; Xu, Guo

doi:10.1186/s12886-019-1292-x

Cited by 17 publications

(17 citation statements)

References 25 publications

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“…However, the frequent injection of those medicines highly enhanced the physical and economic burden of patients. Moreover, the current therapeutic methods including anti-VEGF therapies show several other side effects such as individual specificity [ 6 – 9 ]. Therefore, it is urgent to develop novel methods, which are effective, cheap, and low individual specificity [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway

Xiao

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Control of neovascularization with small molecules is a promising tactics. Here, we tested the roles of sodium butyrate (NaBu) on the neovascularization and primary explained its underlining molecular links. We used models including cell and ex vivo culture of choroid and mouse, as well as the biochemical and cellular techniques, to confirm our hypothesis. We found that treating HUVEC cells with NaBu (both 2.5 mM and 5 mM) significantly inhibited its ability in tube formation and proliferation. This inhibitory effect was also observed in choroid sprouting experiments, compared to the control. Interestingly, the choroid sprouting suppressed by NaBu can proliferate again after removing it, indicating that the cell cycle progression might be arrested. The laser-induced choroid neovascularization (CNV) was significantly alleviated by assessing the CNV size (decreased to 0.73 fold) in contrast with the vehicle control group after 2.5 mM NaBu injection for 7 days. Mechanistically, we found an enhanced TXNIP expression in response to NaBu treatment in all the three models. Overexpressing TXNIP in HUVEC cells blocked its tube formation and inhibited its proliferation; on the other hand, knocking down its expression with shRNA reversed those phenotypes in context of NaBu treatment. Further investigation showed the expression of VEGF receptor 2 (VEGFR2) in HUVEC cells was regulated by TXNIP undergoing NaBu treatment. We therefore argued that NaBu inhibited neovascularization partially through TXNIP-regulated VEGFR2 signal pathway.

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Section: Introductionmentioning

confidence: 99%

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway

Xiao

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Previous studies have also shown that MSCs increase retinal vascular density and reduce the number of acellular capillaries [47] . It is well known that VEGF is an effective factor to promote vascular growth.…”

Section: Discussionmentioning

confidence: 94%

TBHQ Regulates the Nrf2/HO-1 Pathway to Enhance Stem Cell Treatment of Diabetic Retinopathy

Xu¹,

Tian²,

Li³

et al. 2021

Preprint

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Objective: To investigate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic retinopathy (DR) in diabetic rats, and to study the mechanism of hUCMSCs in treating diabetic retinopathy by tert-butylhydroquinone (tBHQ) regulation of the Nrf2/HO-1 pathway.Methods: The diabetic rat model was induced by intraperitoneal injection of streptozotocin (STZ). The experimental animals were divided into six groups: Normal, diabetes mellitus (DM), hUCMSCs, tBHQ, combined tBHQ-hUCMSCs, and all-trans-retinoid acid (ATRA)-hUCMSCs combined group. Visual function experiments and histological analyses were performed eight weeks post intravitreal injection. Biochemical and molecular analyses were used to assess the hUCMSCs composition and its biological effects.Results: Improvements in systemic oxidative stress and inflammation were found in the tBHQ group. Although hUCMSCs had no significant effect on oxidative stress, retinal structure was improved, visual defects reduced and expression of local retinal inflammatory factors were inhibited following its application. The effect of combined therapy was better than that of single therapy. Inhibition of the Nrf2/HO-1 pathway can promote the expression of systemic inflammatory factors and inhibit the therapeutic effect of hUCMSCs in the retina.Conclusions: Intravitreal administration of hUCMSCs triggers an effective cytoprotective microenvironment in the retina of diabetic mice. Alone, however, it may not significantly improve the systemic inflammatory response of diabetes. In combination with tBHQ it may promote Nrf2expression, systemic antioxidant stress and therapeutic effects of hUCMSCs.

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“…Observation for 10 days after transplantation showed that the mBM-MSCs could suppress neovascularization and present a preventive effect on retinopathy induced by oxygen. Moreover, the mBM-MSCs could migrate to the site of damage on retina, reduce the apoptosis of retinal cells and expand the density of retinal vessels [76]. Furthermore, microRNA-9-5p modified mBM-MSCs (miR-9-5p-m-mBM-MSCs) have been used in bone cancer pain therapy in a mouse model.…”

Section: Bone Marrow Mesenchymal Stem Cellsmentioning

confidence: 99%

Human stem cells – sources, sourcing and in vitro methods

Szubarga

Kamińska

Kotlarz

et al. 2021

Medical Journal of Cell Biology

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Stem cells are an important subject of research, and are increasingly used in the treatment of various diseases. Due to the development of advanced in vitro techniques, they have become an integral part of modern medicine. The sources of human stem cells are primarily bone marrow and adipose tissue, although non – embryonic stem cells are also scattered throughout the body. Notably, recent research has focused on stem cells found in the oral cavity, both in the dental pulp and oral mucosa. Furthermore, isolation of stem cells from umbilical cord blood is also becoming increasingly popular, while wharton’s jelly and amniotic fluid also seem to be an interesting source of stem cells. The safety and efficacy of stem cells use can be established by animal studies, which are a key element of preclinical research. Mouse, rat and pig models allow for testing of stem cell therapies. Recent studies primarily use mesenchymal stem cells such as mouse – adipose derived mesenchymal stem cells and mouse and rat hematopoietic stem cells. Great hope for future therapies is the use of bioengineering to program cells into induced stem cells, which have the biggest ability for differentiation and transdifferentiation, which carries no risk of teratogenesis. Stem cells are used in many areas of medicine, especially in regenerative medicine, with a growing interest in orthopedics and in the treatment of heart failure. Mesenchymal stem cells are the most used stem cell type, which despite their limited ability to differentiate, give great therapeutic results, mainly due to their immunomodulating effect. Recent studies have even shown that the use of mesenchymal stem cells may be useful in the treatment of COVID-19. Moreover, Research on the use of mesenchymal stem cells in the treatment of Crohn’s disease, acute-graft-versus-host disease and type I diabetes are also promising. The aim of the current review is to present and systematize current knowledge about stem cells, their use and related in vitro research. Running title: Research and use of human stem cells

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Therapeutic effect against retinal neovascularization in a mouse model of oxygen-induced retinopathy: bone marrow-derived mesenchymal stem cells versus Conbercept

Cited by 17 publications

References 25 publications

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway

TBHQ Regulates the Nrf2/HO-1 Pathway to Enhance Stem Cell Treatment of Diabetic Retinopathy

Human stem cells – sources, sourcing and in vitro methods

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