Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function

Valeria Sordi, Raffaella Melzi, Alessia Mercalli, Roberta Formicola, Claudio Doglioni, Francesca Tiboni, Giuliana Ferrari, Rita Nano, Karolina Chwalek, Eckhard Lammert, Ezio Bonifacio, Lorenzo Piemonti

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Abstract

Adherent fibroblast-like cells have been reported to appear in cultures of human endocrine or exocrine pancreatic tissue during attempts to differentiate human β cells from pancreatic precursors. A thorough characterization of these mesenchymal cells has not yet been completed, and there are no conclusive data about their origin. We demonstrated that the human mesenchymal cells outgrowing from cultured human pancreatic endocrine or exocrine tissue are pancreatic mesenchymal stem cells (pMSC) that propagate from contaminating pMSC. The origin of pMSC is partly extrapancreatic both in humans and mice, and by using green fluorescent protein (GFP+) bone marrow transplantation in the mouse model, we were able to demonstrate that these cells derive from the CD45+ component of bone marrow. The pMSC express negligible levels of islet-specific genes both in basal conditions and after serum deprivation or exogenous growth factor exposure, and might not represent optimal candidates for generation of physiologically competent β-cells. On the other hand, when cotransplanted with a minimal pancreatic islet mass, pMSC facilitate the restoration of normoglycemia and the neovascularization of the graft. These results suggest that pMSCs could exert an indirect role of "helper" cells in tissue repair processes.

Original languageEnglish
Pages (from-to)140-151
Number of pages12
JournalStem Cells
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 2010

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Mesenchymal Stromal Cells
Stem Cells
Bone Marrow
Helper-Inducer T-Lymphocytes
Green Fluorescent Proteins
Bone Marrow Transplantation
Islets of Langerhans
Cultured Cells
Intercellular Signaling Peptides and Proteins
Fibroblasts
Transplants
Serum
Genes

Keywords

  • Islet function
  • Mesenchymal cells
  • Pancreatic tissue

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function. / Sordi, Valeria; Melzi, Raffaella; Mercalli, Alessia; Formicola, Roberta; Doglioni, Claudio; Tiboni, Francesca; Ferrari, Giuliana; Nano, Rita; Chwalek, Karolina; Lammert, Eckhard; Bonifacio, Ezio; Piemonti, Lorenzo.

In: Stem Cells, Vol. 28, No. 1, 01.2010, p. 140-151.

Research output: Contribution to journalArticle

Sordi, Valeria ; Melzi, Raffaella ; Mercalli, Alessia ; Formicola, Roberta ; Doglioni, Claudio ; Tiboni, Francesca ; Ferrari, Giuliana ; Nano, Rita ; Chwalek, Karolina ; Lammert, Eckhard ; Bonifacio, Ezio ; Piemonti, Lorenzo. / Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function. In: Stem Cells. 2010 ; Vol. 28, No. 1. pp. 140-151.
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