title: Co-transplantation of human pancreatic islets with post-migratory neural crest stem cells increases β-cell proliferation and vascular and neural regrowth.
abstract: BACKGROUND
  Neural crest stem cells (NCSCs) are capable of substantially improving murine islet function by promoting β-cell proliferation.
  
  
  OBJECTIVE
  The present study aimed to investigate the potential of NCSCs to stimulate human β-cell proliferation, and improve neural and vascular engraftment of human islets.
  
  
  METHODS
  Human pancreatic islets from 18 brain-dead cadaveric donors (age range, 19-78 y) were obtained through the Nordic Network for Clinical Islet Transplantation. β-cell proliferation and graft function was investigated at our experimental laboratory.
  
  
  METHODS
  Human islets were transplanted, either alone or together with spheres of NCSCs. β-cell proliferation, as well as islet neural and vascular densities, were assessed by immunohistochemistry. Graft blood perfusion and oxygen tension were measured using laser-Doppler flowmetry and Clark microelectrodes, respectively.
  
  
  RESULTS
  Two days posttransplantation, the number of Ki67-positive β-cells was doubled in human islets that had been exposed to NCSCs. Similar findings were obtained in vitro, as well as with EdU as proliferation marker. Four weeks posttransplantation, NCSC-exposed human islet grafts had much higher neural and vascular densities. The newly formed blood vessels were also functional, given that these human islets had a substantially higher blood perfusion and oxygen tension when compared with control transplants.
  
  
  CONCLUSIONS
  We conclude that exposure to NCSCs stimulates human β-cell proliferation, and that these cells improve both the neural and vascular engraftment of transplanted human islets. NCSCs are a promising cellular therapy for translation into clinical use.
authors: Department of Medical Cell Biology (L.G., S.V., Z.L., L.J., P.-O.C.), Department of Neurosciences (S.V., E.K.), Department of Immunology, Genetics and Pathology (J.O.), and Department of Medical Sciences (P.-O.C.), Uppsala University, SE-75123 Uppsala, Sweden.
authors: Liza
authors: L
authors: Grapensparr
authors: Svitlana
authors: S
authors: Vasylovska
authors: Zhanchun
authors: Z
authors: Li
authors: Johan
authors: J
authors: Olerud
authors: Leif
authors: L
authors: Jansson
authors: Elena
authors: E
authors: Kozlova
authors: Per-Ola
authors: PO
authors: Carlsson
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology*; D007515:Islets of Langerhans / Q000098:blood supply / Q000294:innervation / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D009432:Neural Crest / Q000637:transplantation*; D058953:Neural Stem Cells / Q000637:transplantation*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D055815:Young Adult