Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy

Zhang, Wei; Wang, Yuexin; Kong, Jiahui; Meng, Di; Duan, Hongtao; Chen, Song

doi:10.1038/s41598-017-00298-2

Cited by 81 publications

(68 citation statements)

References 25 publications

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“…The decrease in lipofuscin volume can also be explained by the increase in RPE phagocytosis functions. Previous work has also found that many retinal disorders such as diabetic retinopathy, retinal vein occlusion and age-related macular degeneration have low-grade inflammation in their etiopathogenesis [27,28,56,72].…”

Section: Discussionmentioning

confidence: 98%

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Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

Özmert

Arslan

2020

Stem Cell Res Ther

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Purpose: The aim of this study is to determine if umbilical cord Wharton's jelly derived mesenchymal stem cells implanted in sub-tenon space have beneficial effects on visual functions in retinitis pigmentosa patients by reactivating the degenerated photoreceptors in dormant phase. Material and methods:This prospective, open-label, phase-3 clinical trial was conducted between April of 2019 and October of 2019 at Ankara University Faculty of Medicine, Department of Ophthalmology. 32 RP patients (34 eyes) were included in the study. The patients were followed for 6 months after the Wharton's jelly derived mesenchymal stem cell administration, and evaluated with consecutive examinations. All patients underwent a complete routine ophthalmic examination, and best corrected visual acuity, optical coherens tomography angiography, visual field, multifocal and full-field electroretinography were performed. The quantitative results were obtained from a comparison of the pre-injection and final examination (6th month) values.Results: The mean best corrected visual acuity was 70.5 letters prior to Wharton's jelly derived mesenchymal stem cell application and 80.6 letters at the 6th month (p = 0.01). The mean visual field median deviation value was 27.3 dB before the treatment and 24.7 dB at the 6th month (p = 0.01). The mean outer retinal thickness was 100.3 μm before the treatment and 119.1 μm at 6th month (p = 0.01). In the multifocal electroretinography results, P1 amplitudes improved in ring1 from 24.8 to 39.8 nv/deg2 (p = 0.01), in ring2 from 6.8 to 13.6 nv/deg2 (p = 0.01), and in ring3 from 3.1 to 5.7 nv/deg2 (p = 0.02). P1 implicit times improved in ring1 from 44.2 to 32.4 ms (p = 0.01), in ring2 from 45.2 to 33.2 ms (p = 0.02), and in ring3 from 41.9 to 32.4 ms (p = 0.01). The mean amplitude improved in 16 Tds from 2.4 to 5.0 nv/deg2 (p = 0.01) and in 32 Tds from 2.4 to 4.8 nv/deg2 (p = 0.01) in the full-field flicker electroretinography results. Full field flicker electroretinography mean implicit time also improved in 16 Tds from 43.3 to 37.9 ms (p = 0.01). No ocular or systemic adverse events related to the two types of surgical methods and/or Wharton's jelly derived mesenchymal stem cells itself were observed during the follow-up period.Conclusion: RP is a genetic disorder that can result in blindness with outer retinal degeneration. Regardless of the type of genetic mutation, sub-tenon Wharton's jelly derived mesenchymal stem cell administration appears to be an effective and safe option. There are no serious adverse events or ophthalmic / systemic side effects for 6 months follow-up. Although the long-term adverse effects are still unknown, as an extraocular approach, subtenon implantation of the stem cells seems to be a reasonable way to avoid the devastating side effects of intravitreal/submacular injection. Further studies that include long-term follow-up are needed to determine the duration of efficacy and the frequency of application.

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Section: Discussionmentioning

confidence: 98%

“…WJ-MSCs are hypoimmunogenic and have significant immunomodulatory properties. WJ-MSCs have been shown to suppress chronic inflammation and prevent apoptosis in animal models of neurodegenerative and ischemic retinal disorders [27,28]. WJ-MSCs also stimulate progenitor cells in the retina and elicit selfrepair mechanisms [29,30].…”

Section: Introductionmentioning

confidence: 99%

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

Özmert

Arslan

2020

Stem Cell Res Ther

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“…Mesenchymal Stem Cells (MSCs) belong to the subtype of stromal cells which have the capacity for self-renewal as well as differentiation into multiple lineages [40]. They are derived from various tissues like umbilical tissue, embryonic mesoderm, bone marrow, adipose tissue, endometrial polyps [40,41]. MSCs have the ability to clone into adherent fibroblast cells possessing unique cell surface receptors [41].…”

Section: Role Of Mesenchymal Stem Cells To Treat Retinal Disordersmentioning

confidence: 99%

“…They are derived from various tissues like umbilical tissue, embryonic mesoderm, bone marrow, adipose tissue, endometrial polyps [40,41]. MSCs have the ability to clone into adherent fibroblast cells possessing unique cell surface receptors [41]. MSCs can differentiate into endoderm, mesoderm and ectoderm; under regulatory control of various transcription factors.…”

Section: Role Of Mesenchymal Stem Cells To Treat Retinal Disordersmentioning

confidence: 99%

Ocular Stem Cells to Treat Retinal and Corneal Disorders

Chatterji¹,

Mehvash²,

Roma³

2018

TOSCJ

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Background:According to WHO, 285 million people are visually impaired out of which, 39 million are classified as blind and the remaining 246 million people have low vision which comprises of moderate vision impairment and severe vision impairment. Therapies to treat major disorders leading to visual impairment like Age-related Macular Degeneration (AMD), Stargardt’s Disease (STGD), Retinitis Pigmentosa (RP) and corneal scarring are required.In the last decade, many advances have been made to treat these disorders using stem cell therapy. For corneal damage by accidental burns, scarring or limbal stem cell deficiencies which can lead to partial or total blindness, are treated with a risky intervention like keratoplasty. To overcome issues like graft rejection caused by keratoplasty as well as have a better outcome, limbal stem cell therapy has been introduced. Similarly, Retinal Pigment Epithelium (RPE) is a supporting tissue essential in nutrient transport, production of growth factors, phagocytosis of the photoreceptors and retinol cycling.Discussion and Conlusion:Degeneration of this monolayer causes many diseases that have no prevailing treatment; however, research is being carried out to replace this simple epithelial monolayer primarily with an autologous source of cells and currently using stem cells. This review discusses the advances made in the field of ocular stem cell therapy with regards to development, cultivation and novel methods used to deliver these cells to replace the corneal and retinal epithelium as a new standard for treatment.

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“…Since then, the application of eye drops derived from AS (UCB serum, UCBS) or allogeneic serum (allo-S) to treat a wide range of ocular surface diseases, mainly severe dry eye due to either Sjögren syndrome (SS) or ocular graft-versus-host disease (oGVHD), has been explored [3][4][5][6][7]. More recently, stem cells obtained from different sources, including UCB, have been used in cell replacement therapies for a variety of ocular pathologies (ranging from corneal scar to optic nerve degeneration) that are traditionally characterized by poor outcomes when treated with conventional therapies [8][9][10][11][12][13][14][15][16][17]. In the present review, we summarize the various types of products obtained from UCB and their current indications for the treatment of ocular diseases.…”

Section: Introductionmentioning

confidence: 99%

Umbilical Cord Blood and Serum for the Treatment of Ocular Diseases: A Comprehensive Review

et al. 2020

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Several blood derivatives have been proposed for the treatment of various ocular diseases that affect either the anterior or the posterior segment of the eye. Blood sources may range from the patient's own peripheral blood (autologous) to donor tissues, mainly allogeneic peripheral blood and umbilical cord blood (UCB). The utilization of the latter permits the collection of a large amount of serum all at once, and is characterized by therapeutic feasibility in patients with a poor general condition or anemia and blood dyscrasia. Products derived from UCB have two potential uses. First, serum in the form of eye drops can be applied topically onto the ocular surface to efficiently treat anterior segment disorders such as dry eye syndrome or corneal epithelial defects with different etiologies. The rationale for and efficacy of this application derive from the high concentrations of biologically active components and growth factors in UCB, which can nourish the ocular surface. Second, UCB is a source of stem cells, which are used in the field of regenerative medicine because they differentiate into various mature cells, including corneal and retinal cells. Therefore, UCB-derived stem cells have been proposed as a replacement therapy for the treatment of retinal and optic nerve diseases, given that current standard treatments often fail. The present review explores the clinical results that have been obtained using UCBderived products in the field of ophthalmology, as well as the current limitations of those products in this field. Furthermore, given the promising development of UCB-based therapies, possible future directions in this area are discussed.

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Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy

Cited by 81 publications

References 25 publications

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

Ocular Stem Cells to Treat Retinal and Corneal Disorders

Umbilical Cord Blood and Serum for the Treatment of Ocular Diseases: A Comprehensive Review

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