title: Transplantation of insulin-producing cells differentiated from human periosteum-derived progenitor cells ameliorate hyperglycemia in diabetic mice.
abstract: BACKGROUND
  Periosteum-derived progenitor cells (PDPCs) isolated from the adult periosteum can differentiate into several specific cell types. In this study, we examined the characteristics of human PDPCs and insulin-producing cells (IPCs) differentiated from PDPCs and their ability to ameliorate hyperglycemia when transplanted into streptozotocin-induced nonobese diabetic-severe combined immunodeficiency diabetic mice.
  
  
  METHODS
  Periosteum-derived progenitor cells were isolated from patients, expanded in culture, and subjected to a three-step differentiation protocol to produce IPCs. The expression of immunogenic, pluripotent, and pancreatic markers was examined, and glucose-stimulated insulin release in vitro was also assessed. Insulin-producing cells that differentiated from PDPCs were transplanted under the kidney capsule of streptozotocin-induced diabetic mice, and glucose levels and glucose tolerance were measured.
  
  
  RESULTS
  We found that PDPCs expressed the mesenchymal stem cell markers CD73, CD90, and CD105 and the pluripotent markers, octamer-binding transcription factor 4 and Nanog, but not sex-determining region Y-box 2 or Rex1. Periosteum-derived progenitor cells expressed human leukocyte antigen-ABC but did not express human leukocyte antigen-DR or the costimulatory molecules CD80 and CD86. Differentiated IPCs expressed pancreatic hormones (insulin, glucagon, somatostatin, and glucose transporter 2), hormone processing, and secretion molecules (prohormone convertase-1 and convertase-2, Kir6.2), and pancreatic transcription factors (neurogenin 3, pancreatic and duodenal homeobox 1, sex-determining region Y-box 17). When IPCs were stimulated with glucose in vitro, insulin secretion was elevated. Transplantation of IPCs under the kidney capsules of diabetic mice improved hyperglycemia and glucose tolerance. Human insulin was detected in the serum and kidney sections of mice transplanted with IPCs differentiated from PDPCs.
  
  
  CONCLUSIONS
  These results suggest that IPCs differentiated from PDPCs might be an alternative source of β cells for treating diabetes.
authors.affiliation: 1 College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-ku, Incheon, South Korea. 2 Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-ku, Incheon, South Korea. 3 Department of Biological Engineering, Inha University, Incheon, South Korea. 4 Department of Applied Bioscience, CHA University, Seoul, South Korea. 5 Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. 6 Gachon Medical Research Institute, Gil Hospital, Incheon, South Korea. 7 Address correspondence to: Hee-Sook Jun, Ph.D., College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, South Korea.
authors.forename: Lan T M
authors.initials: LT
authors.lastname: Dao
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Park
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lim
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Choi
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Jung
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Jun
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy; D005260:Female; D064593:Heterografts; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000628:therapy*; D007328:Insulin / Q000096:biosynthesis*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010521:Periosteum / Q000166:cytology
chemical_list: D001786:Blood Glucose; D007328:Insulin