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      Therapeutic effects of stem cells from human exfoliated deciduous teeth on diabetic peripheral neuropathy

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          Abstract

          Objective

          To evaluate the therapeutic potential of stem cells from human exfoliated deciduous teeth (SHED) for diabetic peripheral neuropathy.

          Methods

          The biological characteristics of SHED were identified by flow cytometric study and evaluation of differentiation potential. Using high-fat feeding, diabetes was induced in GK rats, and SHED were transplanted into the caudal veins of these rats. Immunohistochemical analysis was used to compare the capillary to muscle fiber ratio and intra-epidermal nerve fiber density between SHED- and saline-treated diabetic rats. Further, the expressions of angiogenesis-related and neurotrophic factors were quantified by real-time PCR and western blot.

          Results

          SHED had a capacity of multiple differentiation and shared typical characteristics of mesenchymal stem cells. SHED transplantation relieved diabetic neuropathic pain, enabled functional recovery of the peripheral nerves, and increased the capillary to muscle fiber ratio and intra-epidermal nerve fiber density compared to the saline group and normal controls. Real-time PCR results showed that the expressions of CD31, vWF, bFGF, NGF, and NT-3 in the skeletal muscles were higher in the SHED group than in the saline groups. Western blot results indicated that the levels of the CD31 and NGF proteins were higher in the SHED transplantation group than the saline group.

          Conclusion

          SHED transplantation ameliorated diabetic peripheral neuropathy in diabetic GK rats. Thus, systemic application of SHED could be a novel strategy for the treatment of diabetic peripheral neuropathy.

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          Most cited references28

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          IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040.

          To produce current estimates of the national, regional and global impact of diabetes for 2015 and 2040.
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            Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth

            Pulp necrosis arrests root development in injured immature permanent teeth, which may result in tooth loss. However, dental pulp regeneration and promotion of root development remains challenging. We show that implantation of autologous tooth stem cells from deciduous teeth regenerated dental pulp with an odontoblast layer, blood vessels, and nerves in two animal models. These results prompted us to enroll 40 patients with pulp necrosis after traumatic dental injuries in a randomized, controlled clinical trial. We randomly allocated 30 patients to the human deciduous pulp stem cell (hDPSC) implantation group and 10 patients to the group receiving traditional apexification treatment. Four patients were excluded from the implantation group due to loss at follow-up (three patients) and retrauma of the treated tooth (one patient). We examined 26 patients (26 teeth) after hDPSC implantation and 10 patients (10 teeth) after apexification treatment. hDPSC implantation, but not apexification treatment, led to regeneration of three-dimensional pulp tissue equipped with blood vessels and sensory nerves at 12 months after treatment. hDPSC implantation increased the length of the root (P < 0.0001) and reduced the width of the apical foramen (P < 0.0001) compared to the apexification group. In addition, hDPSC implantation led to regeneration of dental pulp tissue containing sensory nerves. To evaluate the safety of hDPSC implantation, we followed 20 patients implanted with hDPSCs for 24 months and did not observe any adverse events. Our study suggests that hDPSCs are able to regenerate whole dental pulp and may be useful for treating tooth injuries due to trauma.
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              Immunomodulatory properties of stem cells from human exfoliated deciduous teeth

              Introduction Stem cells from human exfoliated deciduous teeth (SHED) have been identified as a population of postnatal stem cells capable of differentiating into osteogenic and odontogenic cells, adipogenic cells, and neural cells. Herein we have characterized mesenchymal stem cell properties of SHED in comparison to human bone marrow mesenchymal stem cells (BMMSCs). Methods We used in vitro stem cell analysis approaches, including flow cytometry, inductive differentiation, telomerase activity, and Western blot analysis to assess multipotent differentiation of SHED and in vivo implantation to assess tissue regeneration of SHED. In addition, we utilized systemic SHED transplantation to treat systemic lupus erythematosus (SLE)-like MRL/lpr mice. Results We found that SHED are capable of differentiating into osteogenic and adipogenic cells, expressing mesenchymal surface molecules (STRO-1, CD146, SSEA4, CD73, CD105, and CD166), and activating multiple signaling pathways, including TGFβ, ERK, Akt, Wnt, and PDGF. Recently, BMMSCs were shown to possess an immunomodulatory function that leads to successful therapies for immune diseases. We examined the immunomodulatory properties of SHED in comparison to BMMSCs and found that SHED had significant effects on inhibiting T helper 17 (Th17) cells in vitro. Moreover, we found that SHED transplantation is capable of effectively reversing SLE-associated disorders in MRL/lpr mice. At the cellular level, SHED transplantation elevated the ratio of regulatory T cells (Tregs) via Th17 cells. Conclusions These data suggest that SHED are an accessible and feasible mesenchymal stem cell source for treating immune disorders like SLE.
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                Author and article information

                Contributors
                xj1056@163.com
                raonanquan@163.com
                zhaiyuekouqiang@yeah.net
                mynameisljz1994@163.com
                yuming_zhao@hotmail.com
                gelh0919@126.com
                8610 82195306 , cwyyd@126.com
                Journal
                Diabetol Metab Syndr
                Diabetol Metab Syndr
                Diabetology & Metabolic Syndrome
                BioMed Central (London )
                1758-5996
                17 May 2019
                17 May 2019
                2019
                : 11
                : 38
                Affiliations
                [1 ]ISNI 0000 0001 2256 9319, GRID grid.11135.37, Department of Pediatric Dentistry, School and Hospital of Stomatology, , Peking University, ; #22 Zhongguancun Nandajie, Haidian District, Beijing, 100081 China
                [2 ]ISNI 0000 0004 1806 5224, GRID grid.452787.b, Department of Stomatology, , Shenzhen Children’s Hospital, ; #7019, Yitian Road, Shenzhen, 518026 China
                Article
                433
                10.1186/s13098-019-0433-y
                6525430
                31131042
                e96d957e-beb0-4137-b756-540ca24558d3
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 March 2019
                : 7 May 2019
                Funding
                Funded by: National Natural Science Youth Foundation of China
                Award ID: 81500837
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Nutrition & Dietetics
                stem cells from human exfoliated deciduous teeth,diabetic peripheral neuropathy,goto-kakizaki rats,stem cell therapy

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