title: Biologic and immunomodulatory properties of mesenchymal stromal cells derived from human pancreatic islets.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSC) have now been shown to reside in numerous tissues throughout the body, including the pancreas. Ex vivo culture-expanded MSC derived from many tissues display important interactions with different types of immune cells in vitro and potentially play a significant role in tissue homeostasis in vivo. In this study, we investigated the biologic and immunomodulatory properties of human pancreatic islet-derived MSC.
  
  
  METHODS
  We culture-expanded MSC from cadaveric human pancreatic islets and characterized them using flow cytometry, differentiation assays and nuclear magnetic resonance-based metabolomics. We also investigated the immunologic properties of pancreatic islet-derived MSC compared with bone marrow (BM) MSC.
  
  
  RESULTS
  Pancreatic islet and BM-derived MSC expressed the same cell-surface markers by flow cytometry, and both could differentiate into bone, fat and cartilage. Metabolomics analysis of MSC from BM and pancreatic islets also showed a similar set of metabolic markers but quantitative polymerase chain reactions showed that pancreatic islet MSC expressed more interleukin(IL)-1b, IL-6, STAT3 and FGF9 compared with BM MSC, and less IL-10. However, similar to BM MSC, pancreatic islet MSC were able to suppress proliferation of allogeneic T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies.
  
  
  CONCLUSIONS
  Our in vitro analysis shows pancreatic islet-derived MSC have phenotypic, biologic and immunomodulatory characteristics similar, but not identical, to BM-derived MSC. We propose that pancreatic islet-derived MSC could potentially play an important role in improving the outcome of pancreatic islet transplantation by promoting engraftment and creating a favorable immune environment for long-term survival of islet allografts.
authors.affiliation: University of Wisconsin-Madison, School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Jaehyup
authors.initials: J
authors.lastname: Kim
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Breunig
authors.forename: Leah E
authors.initials: LE
authors.lastname: Escalante
authors.forename: Neehar
authors.initials: N
authors.lastname: Bhatia
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Denu
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Dollar
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Stein
authors.forename: Summer E
authors.initials: SE
authors.lastname: Hanson
authors.forename: Nadia
authors.initials: N
authors.lastname: Naderi
authors.forename: James
authors.initials: J
authors.lastname: Radek
authors.forename: Dermot
authors.initials: D
authors.lastname: Haughy
authors.forename: Debra D
authors.initials: DD
authors.lastname: Bloom
authors.forename: Fariba M
authors.initials: FM
authors.lastname: Assadi-Porter
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
mesh_terms: D000954:Antigens, Surface / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002102:Cadaver; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface