title: Pancreatic differentiation of human dental pulp CD117⁺ stem cells.
abstract: OBJECTIVE
  Adult stem cells cannot proliferate to produce enough cells for human transplantation with keeping stem cell characteristics shown in the primary culture. We established a novel culture protocol using human dental pulp stem cells (DPSCs) that can produce quantities sufficient for human transplantation. The present study assessed differentiation of DPSCs toward a pancreatic lineage in serum-free conditions, which is essential for safe transplantation.
  
  
  METHODS
  CD117⁺ stem cells were separated from human exfoliated deciduous teeth (stem cells from human exfoliated deciduous teeth; SHED) and adult DPSCs. The cells were characterized with real-time reverse-transcription PCR for a panel of embryonal lineage markers.
  
  
  RESULTS
  82 out of 84 markers were expressed in different levels in SHED or DPSCs. After pancreatic differentiation in vitro, we found expression of pancreatic-specific endocrine markers insulin, glucagon, somatostatin and pancreatic polypeptide, and exocrine marker amylase-2a in both cultures. We also found reprogramming in both cell cultures mimicking the embryonal stages of development of the pancreas. Transcription factors PDX1, HHEX, MNX1, NEUROG3, PAX4, PAX6 and NKX6-1, crucial markers for the pancreatic development, were all activated. Expression of these factors strongly implies that the cells differentiated toward a distinguished pancreatic lineage.
  
  
  CONCLUSIONS
  Our results show that CD117⁺ SHED and DPSCs are capable of differentiation toward all functional endocrine and exocrine subsets of pancreatic cells in serum-free conditions. SHED and DPSCs may therefore have great potential for future cell therapy of pancreatic disorders.
authors.affiliation: Nippon Dental University, School of Life Dentistry at Tokyo, Department of Oral Health, 1-9-20 Chiyoda-ku, 102-8159 Tokyo, Japan.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Ishkitiev
authors.forename: Ken
authors.initials: K
authors.lastname: Yaegaki
authors.forename: Ana
authors.initials: A
authors.lastname: Kozhuharova
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Mio
authors.initials: M
authors.lastname: Okada
authors.forename: Vanyo
authors.initials: V
authors.lastname: Mitev
authors.forename: Masaomi
authors.initials: M
authors.lastname: Fukuda
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D003782:Dental Pulp / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D010179:Pancreas / Q000166:cytology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014094:Tooth, Deciduous / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit