title: Bone marrow transplantation temporarily improves pancreatic function in streptozotocin-induced diabetes: potential involvement of very small embryonic-like cells.
abstract: BACKGROUND
  The role of bone marrow (BM)-derived cells in pancreatic beta-cell regeneration remains unresolved. We examined whether BM-derived cells are recruited to the site of moderate pancreatic injury and contribute to beta-cell regeneration.
  
  
  METHODS
  Low-dose streptozotocin (STZ) treatment was used to induce moderate pancreatic damage and hyperglycemia. Enhanced green fluorescent protein-positive (EGFP) BM chimeras were evaluated for beta-cell regeneration after STZ treatment.
  
  
  RESULTS
  To test the hypothesis that pancreatic tissue injury induces a stromal cell-derived factor (SDF)-1 gradient to chemoattract the stem cells, we evaluated the expression of mRNA for SDF-1 in damaged pancreatic tissue. SDF-1 was significantly increased in the pancreas after damage, peaking at day 10. The majority of BM cells expressing mRNA for pancreatic development markers were detected in the subpopulation of CD45/Sca-1/Lin very small embryonic-like (VSEL) cells. VSEL cells mobilized from BM to peripheral blood in response to pancreatic damage, peaking in peripheral blood at day 5, and were enriched in the pancreas 10 to 15 days after STZ treatment. To confirm a role for BM-derived cells in pancreatic beta-cell regeneration, we prepared EGFP-->B6 chimeras. In the EGFP chimeras, EGFP cells were detected around duct and islets and were positive for insulin after STZ treatment. However, STZ-induced hyperglycemia was reduced only transiently (49-77 days) after pancreatic injury.
  
  
  CONCLUSIONS
  These data suggest that VSEL cells are mobilized into injured pancreatic tissue and contribute to beta-cell regeneration. Transplantation of BM-derived cells improves the function of injured pancreas, although the response is not sufficient to restore sustained normoglycemia.
authors.affiliation: Institute for Cellular Therapeutics, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Huang
authors.forename: Magda
authors.initials: M
authors.lastname: Kucia
authors.forename: Lala-Rukh
authors.initials: LR
authors.lastname: Hussain
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wen
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.forename: Suzanne T
authors.initials: ST
authors.lastname: Ildstad
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D018507:Gene Expression Regulation, Developmental; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration; D013997:Time Factors; D018183:Transplantation Chimera
chemical_list: D001786:Blood Glucose; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D007328:Insulin; D008565:Membrane Proteins; D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse