Light-induced retinal injury enhanced neurotrophins secretion and neurotrophic effect of mesenchymal stem cells in vitro

Xu, Wei; Wang, Xiaoting; Xu, Guo; Guo, Jiansheng

doi:10.1590/s0004-27492013000200010

Cited by 13 publications

(7 citation statements)

References 24 publications

(25 reference statements)

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“…Angiogenic factors, such as bFGF and VEGF, could be useful for the treatment of diabetic polyneuropathy. Stem/progenitor cells could have the ability to secrete bFGF and VEGF if transplanted for the treatment of diabetic polyneuropathy .…”

Section: Discussionmentioning

confidence: 99%

Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy

Omi

Hara

Nakamura

et al. 2015

J of Diabetes Invest

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Aims/IntroductionDental pulp stem cells (DPSCs) are thought to be an attractive candidate for cell therapy. We recently reported that the transplantation of DPSCs increased nerve conduction velocity and nerve blood flow in diabetic rats. In the present study, we investigated the immunomodulatory effects of DPSC transplantation on diabetic peripheral nerves.Materials and Methods DPSCs were isolated from the dental pulp of Sprague–Dawley rats and expanded in culture. Eight weeks after the streptozotocin injection, DPSCs were transplanted into the unilateral hindlimb skeletal muscles. Four weeks after DPSC transplantation, neurophysiological measurements, inflammatory gene expressions and the number of CD68‐positive cells in sciatic nerves were assessed. To confirm the immunomodulatory effects of DPSCs, the effects of DPSC‐conditioned media on lipopolysaccharide‐stimulated murine macrophage RAW264.7 cells were investigated.ResultsDiabetic rats showed significant delays in sciatic nerve conduction velocities and decreased sciatic nerve blood flow, all of which were ameliorated by DPSC transplantation. The number of CD68‐positive monocytes/macrophages and the gene expressions of M1 macrophage‐expressed cytokines, tumor necrosis factor‐α and interleukin‐1β, were increased in the sciatic nerves of the diabetic rats. DPSC transplantation significantly decreased monocytes/macrophages and tumor necrosis factor‐α messenger ribonucleic acid expression, and increased the gene expression of the M2 macrophage marker, CD206, in the sciatic nerves of the diabetic rats. The in vitro study showed that DPSC‐conditioned media significantly increased the gene expressions of interleukin‐10 and CD206 in lipopolysaccharide‐stimulated RAW264.7 cells.ConclusionsThese results suggest that DPSC transplantation promoted macrophages polarization towards anti‐inflammatory M2 phenotypes, which might be one of the therapeutic mechanisms for diabetic polyneuropathy.

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Section: Discussionmentioning

confidence: 99%

Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy

Omi

Hara

Nakamura

et al. 2015

J of Diabetes Invest

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“…For example, intrinsic BDNF/ cAMP response element-binding protein (CREB) signaling plays an important role against the apoptosis, inflammation, and oxidative stress induced by nicotine-induced neurotoxicity, 17 and endogenous BDNF was reported to increase Bcl-2 protein levels and reduce Bax levels. 18,19 Light-induced retinal injury and some treatments were also shown to promote the intrinsic generation of BDNF and CNTF, which upregulates Bcl-2 and downregulates Bax, 20,21 while the systemic administration of CNTF promoted the neuroprotection of motor neurons through increasing Bcl-2 and decreasing Bax. 22 Moreover, a single intravitreal injection of CNTF protein was found to increase the Bcl-2/Bax ratio in the retina after laser injury to improve cone survival, 23 and single CNTF use protected photoreceptors of animal models with inherited retinal degeneration.…”

Section: Discussionmentioning

confidence: 99%

Impact of neurotrophic factors combination therapy on retinitis pigmentosa

Yin

Chen

et al. 2020

J Int Med Res

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Objective We aimed to determine the location of neurotrophic receptors tropomyosin receptor kinase (Trk)B, TrkC, and ciliary neurotrophic factor receptor (CNTFR)α in the retina of retinal degeneration ( rd) mice and to explore the dynamic changes of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X-protein (Bax), and microtubule-associated protein light chain 3 (LC3) expression and ultrastructure in the retina of rd mice intravitreally injected with neurotrophic factors. Methods Rd mice aged 2 and 3 weeks post-natally (PN) received intravitreal injections of neurotrophic factors. Two weeks later, their retinas were harvested for the detection of Bax, Bcl-2, and LC3 mRNA and protein expression. Results TrkB and TrkC expression levels were lower at 3 weeks PN compared with 0, 1, and 2 weeks PN, but CNTFRα expression was still detected in certain layers. The three receptors were expressed in different retinal layers at the same timepoint. Bax expression was downregulated in, rhBDNF + rhCNTF, rhBDNF + rhNT-3, groups 2 weeks after intravitreal injection; Bcl-2 expression was upregulated in the rhBDNF + rhCNTF + rhNT-3 group at PN-4w; and LC3 expression was upregulated in rhBDNF + rhCNTF + rhNT-3 groups. Conclusions The combined use of neurotrophic factors had a more significant effect on Bax, Bcl-2, and LC3 expression than the same factors used alone.

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“…In another study, Zhang and Wang 81 found that intravitreally injected BM-MSCs could express brain-derived neurotrophic factor (BDNF) and protect the outer nuclear layer in light-damaged retina. Xu et al 29 , 30 also reported that MSCs could secret basic fibroblast growth factor and exhibit neuroprotective effects in light-damaged retina. Importantly, not only intravitreal injection but also intravenous injection of MSC could achieve retinal protective effects.…”

Section: Roles Of Bm-mscs On Retinal Microenvironmental Regulationmentioning

confidence: 99%

“…Xu et al 29 , 30 found that intravitreal injection of BM-MSCs could suppress microglia activation, thereby reducing the retinal injury.…”

Section: Roles Of Bm-mscs On Retinal Microenvironmental Regulationmentioning

confidence: 99%

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Stem cell therapies for age-related macular degeneration: the past, present, and future

Dang¹,

Zhang²,

Zhu³

2015

CIA

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In the developed world, age-related macular degeneration (AMD) is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD) has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD), which is characterized by retinal pigment epithelial (RPE) cell death (or dysfunction) and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells) by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed.

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Light-induced retinal injury enhanced neurotrophins secretion and neurotrophic effect of mesenchymal stem cells in vitro

Cited by 13 publications

References 24 publications

Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy

Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy

Impact of neurotrophic factors combination therapy on retinitis pigmentosa

Stem cell therapies for age-related macular degeneration: the past, present, and future

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