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Transplantation of islet-like cell clusters derived from human dental pulp stem cells restores normoglycemia in diabetic mice
Authors:Mohammad Mahboob Kanafi  Yajaman Bajjappa Rajeshwari  Sarita Gupta  Nidheesh Dadheech  Prabha Damodaran Nair  Pawan Kumar Gupta  Ramesh Ramchandra Bhonde
Affiliation:1. Manipal Institute of Regenerative Medicine, Manipal University, Bangalore, India;2. Department of Livestock Production Management, Veterinary College KVAFSU, Bangalore, India;3. Department of Biochemistry, The Maharaja Sayajirao University of Baroda, Baroda, India;4. Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India;1. Department of Conservative Dentistry, Faculty of Dentistry Universitas Gadjah Mada, Jl Denta Sekip Utara, Yogyakarta, 55281, Indonesia;2. Department of Dental Biomedical Sciences, Faculty of Dentistry Universitas Gadjah Mada, Jl Denta Sekip Utara, Yogyakarta, 55281, Indonesia;1. Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania;2. Department of Neurobiology and Biophysics, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania;1. Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul, South Korea;2. Department of Pediatric Dentistry, College of Dentistry, Yonsei University, Seoul, South Korea;3. Department of Biomaterials & Prosthodontics, Kyung Hee University Hospital at Gangdong, School of Dentistry, Kyung Hee University, Seoul, South Korea;4. Department of Conservative Dentistry, College of Dentistry, Yonsei University, Seoul, South Korea
Abstract:Background aimsThe success of islet transplantation for diabetes depends on the availability of an adequate number of allogeneic or autologous islets. Postnatal stem cells are now considered for the generation of physiologically competent, insulin-producing cells. Our group showed earlier that it is possible to generate functional islets from human dental pulp stem cells by using a serum-free cocktail in a three-step protocol.MethodsWe compared the yield of generated islet-like cell clusters (ICCs) from stem cells from pulps of human exfoliated deciduous teeth (SHED) and dental pulp stem cells from permanent teeth (DPSCs). ICCs derived from SHED were packed in immuno-isolatory biocompatible macro-capsules and transplanted into streptozotocin (STZ)-induced diabetic mice. Non-diabetic and diabetic controls were transplanted with macro-capsules with or without islets.ResultsSHED were superior to DPSCs. STZ diabetic mice alone and mice transplanted with empty macro-capsules exhibited hyperglycemia throughout the experiment, whereas mice transplanted with macro-capsules containing ICCs were restored to normoglycemia within 3–4 weeks, which persisted for >60 days.ConclusionsOur results demonstrate for the first time that ICCs derived from SHED reverse STZ diabetes in mice without immunosuppression and offer an autologous and non-controversial source of human tissue that could be used for stem cell therapy in diabetes.
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