Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo

Wang, Jian; Zhang, Wei; He, Gang; Wu, Bin; Song, Chunli

doi:10.18240/ijo.2018.05.08

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…In addition to transplanting stem cells and their derivatives, future therapeutic options can include cotransplantation of two or more types of cells to achieve a better clinical benefit. 16,60 Further, stem cells can be modified to overexpress retinal regenerative factors, 31,32,61 and utilization of scaffolds to culture and transplant the stem cells and their derivations might improve their clinical benefits. 62,63 However, there is a lack of consensus on the route of administration, method of evaluation of outcome, source of stem cells, and the long-term effect of stem cell transplantations.…”

Section: Discussionmentioning

confidence: 99%

“… 28 Similar reductions in vascular leakage and improvements in visual acuity were observed when CM derived from human AD-MSCs were intravitreally injected in Ins2 Akita mouse model of DR. 29 Murine BM-MSCs genetically modified to produce neurotrophin-4 preserved the retinal bioelectrical activity in the injured retina and completely restored the laminated organization of the outer retina in an RP animal model. 30 Similarly, BM-MSCs genetically engineered to express C-X-C chemokine receptor type 4, 31 or PEDF 32 significantly reduced the retinal damage, reduced the level of pro-inflammatory cytokines, and restored the retinal structure and function in DR disease models. Interestingly, the administration of neural stem cells derived from UC-MSCs significantly improved the vision and survival of RGCs in diabetic rats.…”

Section: Preclinical Studies With Stem Cellsmentioning

confidence: 96%

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Stem Cell Therapy for Retinal Degeneration: The Evidence to Date

Sharma

Jaganathan

2021

BTT

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There is a rise in the number of people who have vision loss due to retinal diseases, and conventional therapies for treating retinal degeneration fail to repair and regenerate the damaged retina. Several studies in animal models and human trials have explored the use of stem cells to repair the retinal tissue to improve visual acuity. In addition to the treatment of age-related macular degeneration (AMD) and diabetic retinopathy (DR), stem cell therapies were used to treat genetic diseases such as retinitis pigmentosa (RP) and Stargardt's disease, characterized by gradual loss of photoreceptor cells in the retina. Transplantation of retinal pigment epithelial (RPE) cells derived from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have shown promising results in improving retinal function in various preclinical models of retinal degeneration and clinical studies without any severe side effects. Mesenchymal stem cells (MSCs) were utilized to treat optic neuropathy, RP, DR, and glaucoma with positive clinical outcomes. This review summarizes the preclinical and clinical evidence of stem cell therapy and current limitations in utilizing stem cells for retinal degeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Preclinical Studies With Stem Cellsmentioning

confidence: 96%

Stem Cell Therapy for Retinal Degeneration: The Evidence to Date

Sharma

Jaganathan

2021

BTT

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“…In particular, compared to control conditions, EVs from BMSCs overexpressing miRNA-486-3p were able to inhibit Toll-like receptor 4-mediated oxidative stress, inflammation and apoptosis, as well as promoting Müller cell proliferation[ 30 ]. BMSC ability to home to the injury site is guided by SDF-1 through its C-X-C chemokine receptor type 4 (CXCR4)[ 31 ]. To improve this ability, MSCs were infected by a lentivirus constructed with CXCR4.…”

Section: Diabetic Retinopathymentioning

confidence: 99%

Potential therapeutic applications of mesenchymal stem cells for the treatment of eye diseases

Mannino¹,

Russo²,

Longo³

et al. 2021

WJSC

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Stem cell-based treatments have been extensively explored in the last few decades to develop therapeutic strategies aimed at providing effective alternatives for those human pathologies in which surgical or pharmacological therapies produce limited effects. Among stem cells of different sources, mesenchymal stem cells (MSCs) offer several advantages, such as the absence of ethical concerns, easy harvesting, low immunogenicity and reduced tumorigenesis risks. Other than a multipotent differentiation ability, MSCs can release extracellular vesicles conveying proteins, mRNA and microRNA. Thanks to these properties, new therapeutic approaches have been designed for the treatment of various pathologies, including ocular diseases. In this review, the use of different MSCs and different administration strategies are described for the treatment of diabetic retinopathy, glaucoma, and retinitis pigmentosa. In a large number of investigations, positive results have been obtained by in vitro experiments and by MSC administration in animal models. Most authors agree that beneficial effects are likely related to MSC paracrine activity. Based on these considerations, many clinical trials have already been carried out. Overall, although some adverse effects have been described, promising outcomes are reported. It can be assumed that in the near future, safer and more effective protocols will be developed for more numerous clinical applications to improve the quality of life of patients affected by eye diseases.

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“…Since the inflammatory response promotes the secretion of SDF-1, MSCs may express more CXCR4 when the human body is in an inflammatory state. Besides, MSCs with higher CXCR4 expression were considered to have more robust tissue-regeneration capacities, and this could be proved by transfecting CXCR4 into MSCs or using other methods further to increase CXCR4 expression levels ( 139 , 140 ). Furthermore, CXCR4 transfection did not affect the biological characteristics and vitality of BM-MSCs ( 141 ) but enhanced the targeted recruitment and survival of transplanted MSCs ( 142 ).…”

Section: Cell Surface Receptor-mediated Mscs Immunosuppressionmentioning

confidence: 99%

“…On the other hand, CXCR4 deficiency suppresses the immunomodulatory and homing abilities of MSCs ( 144 ). These lead to the downregulation of inflammatory cytokines IL-6 and TNF-α and up-regulation of anti-inflammatory IL-10 ( 140 , 143 ).…”

Section: Cell Surface Receptor-mediated Mscs Immunosuppressionmentioning

confidence: 99%

Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

Liu

Zhou

et al. 2020

Front. Immunol.

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In the past decade, mesenchymal stem cells (MSCs) tend to exhibit inherent tropism for refractory inflammatory diseases and engineered MSCs have appeared on the market as therapeutic agents. Recently, engineered MSCs target to cell surface molecules on immune cells has been a new strategy to improve MSC applications. In this review, we discuss the roles of multiple receptors (ICAM-1, Gal-9, PD-L1, TIGIT, CD200, and CXCR4) in the process of MSCs' immunosuppressive properties. Furthermore, we discuss the principles and strategies for developing receptor-regulated MSCs and their mechanisms of action and the challenges of using MSCs as immunosuppressive therapies.

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Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo

Abstract: The homing of MSCs can be enhanced by upregulating CXCR4 levels, possibly improving histological structures of DR. CXCR4-overexpressing MSCs can be a novel strategy for treating DR.

Cited by 10 publications

References 23 publications

Stem Cell Therapy for Retinal Degeneration: The Evidence to Date

Stem Cell Therapy for Retinal Degeneration: The Evidence to Date

Potential therapeutic applications of mesenchymal stem cells for the treatment of eye diseases

Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

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