title: Generation of monocyte-derived insulin-producing cells from non-human primates according to an optimized protocol for the generation of PCMO-derived insulin-producing cells.
abstract: OBJECTIVE
  The vision of potential autologous cell therapy for the cure of diabetes encourages ongoing research. According to a previously published protocol for the generation of insulin-producing cells from human monocytes, we analyzed whether the addition of growth factors could increase insulin production. This protocol was then transferred to a non-human primate model by using either blood- or spleen-derived monocytes.
  
  
  METHODS
  Human monocytes were treated to dedifferentiate into programmable cells of monocytic origin (PCMO). In addition to the published protocol, PCMOs were then treated with either activin A, betacellulin, exendin 3 or 4. Cells were characterized by protein expression of insulin, Pdx-1, C-peptide and Glut-2. After identifying the optimal protocol, monocytes from baboon blood were isolated and the procedure was repeated. Spleen monocytes following splenectomy of a live baboon were differentiated and analyzed in the same manner and calculated in number and volume.
  
  
  RESULTS
  Insulin content of human cells was highest when cells were treated with activin A and their insulin content was 13,000 µU/1 million cells. Insulin-producing cells form primate monocytes could successfully be generated despite using human growth factors and serum. Expression of insulin, Pdx-1, C-peptide and Glut-2 was comparable to that of human neo-islets. Total insulin content of activin A-treated baboon monocytes was 16,000 µU/1 million cells.
  
  
  CONCLUSIONS
  We were able to show that insulin-producing cells can be generated from baboon monocytes with human growth factors. The amount generated from one spleen could be enough to cure a baboon from experimentally induced diabetes in an autologous cell transplant setting.
authors.affiliation: University Hospital Essen, Department of General, Visceral and Transplantation Surgery, Hufelandstrasse 55, 45147 Essen, Germany. E-ma-il: maren.schulze@uk-essen.de.
authors.forename: Jessica
authors.initials: J
authors.lastname: Walter
authors.forename: Ole
authors.initials: O
authors.lastname: Harder
authors.forename: Fred
authors.initials: F
authors.lastname: Faendrich
authors.forename: Maren
authors.initials: M
authors.lastname: Schulze
mesh_terms: D028341:Activins / Q000494:pharmacology; D000818:Animals; D066259:Betacellulin / Q000494:pharmacology; D002096:C-Peptide / Q000096:biosynthesis; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D051273:Glucose Transporter Type 2 / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010215:Papio / Q000601:surgery; D013156:Splenectomy; D015534:Trans-Activators / Q000096:biosynthesis
chemical_list: D066259:Betacellulin; D002096:C-Peptide; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C422405:activin A; C084010:pancreatic and duodenal homeobox 1 protein; D028341:Activins