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

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          Abstract

          The aim of this study was to evaluate the effects of intravitreal injection of neural stem cells (NSCs) originating from human umbilical cord-derived mesenchymal stem cells (UC-MSCs) on neurodegeneration of diabetic retinopathy (DR) in rats. UC-MSCs were isolated and passaged, followed by induction to NSCs in neural differentiation medium. Four weeks following NSC transplantation, treatment attenuated retinal vascular dysfunction compared with non-treated rats, and BDNF and Thy-1 expression was significantly higher in the treated group than in the control group. Treatment of diabetic rats with NSCs prevented the decrease in BDNF levels caused by diabetes. The average leakage of Evans Blue (EB) dye in the treated group was significantly less than that in the control group. These morphological improvements were accompanied by a restoration of vision, as documented by F-ERG. NSCs originating from MSCs demonstrated a neuroprotective effect by increasing the number of surviving RGCs and significantly reducing the progression of DR. Thus, transplantation of NSCs could be a novel strategy for the treatment of neurodegeneration in DR.

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          Comparative Analysis of Human Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Umbilical Cord Blood as Sources of Cell Therapy

          Various source-derived mesenchymal stem cells (MSCs) have been considered for cell therapeutics in incurable diseases. To characterize MSCs from different sources, we compared human bone marrow (BM), adipose tissue (AT), and umbilical cord blood-derived MSCs (UCB-MSCs) for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, and paracrine activity. Although MSCs from different tissues have similar levels of surface antigen expression, immunosuppressive activity, and differentiation ability, UCB-MSCs had the highest rate of cell proliferation and clonality, and significantly lower expression of p53, p21, and p16, well known markers of senescence. Since paracrine action is the main action of MSCs, we examined the anti-inflammatory activity of each MSC under lipopolysaccharide (LPS)-induced inflammation. Co-culture of UCB-MSCs with LPS-treated rat alveolar macrophage, reduced expression of inflammatory cytokines including interleukin-1α (IL-1α), IL-6, and IL-8 via angiopoietin-1 (Ang-1). Using recombinant Ang-1 as potential soluble paracrine factor or its small interference RNA (siRNA), we found that Ang-1 secretion was responsible for this beneficial effect in part by preventing inflammation. Our results demonstrate that primitive UCB-MSCs have biological advantages in comparison to adult sources, making UCB-MSCs a useful model for clinical applications of cell therapy.
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            Umbilical cord-derived mesenchymal stem cells: Their advantages and potential clinical utility.

            Human umbilical cord (UC) is a promising source of mesenchymal stem cells (MSCs). Apart from their prominent advantages, such as a painless collection procedure and faster self-renewal, UC-MSCs have shown the ability to differentiate into three germ layers, to accumulate in damaged tissue or inflamed regions, to promote tissue repair, and to modulate immune response. There are diverse protocols and culture methods for the isolation of MSCs from the various compartments of UC, such as Wharton's jelly, vein, arteries, UC lining and subamnion and perivascular regions. In this review, we give a brief introduction to various compartments of UC as a source of MSCs and emphasize the potential clinical utility of UC-MSCs for regenerative medicine and immunotherapy.
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              Mesenchymal Stem Cells from Human Umbilical Cord Express Preferentially Secreted Factors Related to Neuroprotection, Neurogenesis, and Angiogenesis

              Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton’s jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. We isolated MSCs from Wharton’s jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their secretomes. It was found that WJ-MSCs expressed more genes, especially secreted factors, involved in angiogenesis and neurogenesis. Functional validation showed that WJ-MSCs induced better neural differentiation and neural cell migration via a paracrine mechanism. Moreover, WJ-MSCs afforded better neuroprotection efficacy because they preferentially enhanced neuronal growth and reduced cell apoptotic death of primary cortical cells in an oxygen-glucose deprivation (OGD) culture model that mimics the acute ischemic stroke situation in humans. In terms of angiogenesis, WJ-MSCs induced better microvasculature formation and cell migration on co-cultured endothelial cells. Our results suggest that WJ-MSC, because of a unique secretome, is a better MSC source to promote in vivo neurorestoration and endothelium repair. This study provides a basis for the development of cell-based therapy and carrying out of follow-up mechanistic studies related to MSC biology.
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                Author and article information

                Contributors
                chensong20@hotmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                24 March 2017
                24 March 2017
                2017
                : 7
                : 1
                : 408
                Affiliations
                ISNI 0000 0000 9792 1228, GRID grid.265021.2, Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, , Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, ; Tianjin, 300020 China
                Article
                298
                10.1038/s41598-017-00298-2
                5412648
                28341839
                9bf725dd-0bb8-4556-b1e6-f9d9f09414dc
                © The Author(s) 2017

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 22 July 2016
                : 17 February 2017
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